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Sample records for corynebacterium glutamicum metabolic

  1. Optimization of lysine metabolism in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Rytter, Jakob Vang

    ,000,000 tons. The aim of this project is to optimize the yield of lysine in C. glutamicum using metabolic engineering strategies. According to a genome scale model of C. glutamicum, theoretically there is much room for increasing the lysine yield (Kjeldsen and Nielsen 2009). Lysine synthesis requires NADPH......Commercial pig and poultry production use the essential amino acid lysine as a feed additive with the purpose of optimizing the feed utilization. Lysine is produced by a fermentation process involving either Corynebacterium glutamicum or Escherichia coli. The global annual production is around 1...... the project intends to eliminate. PGI catalyzes the conversion of alpha-D-glucose-6-phosphate to fructose-6-phosphate just downstream of the branch in the glycolysis, but it also catalyzes the reverse reaction. It is unknown whether up- or down-regulation of the pgi is required to increase the flux through...

  2. Patchoulol Production with Metabolically Engineered Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Nadja A. Henke

    2018-04-01

    Full Text Available Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. Corynebacterium glutamicum is the prominent host for the fermentative production of amino acids with an average annual production volume of ~6 million tons. Due to its robustness and well established large-scale fermentation, C. glutamicum has been engineered for the production of a number of value-added compounds including terpenoids. Both C40 and C50 carotenoids, including the industrially relevant astaxanthin, and short-chain terpenes such as the sesquiterpene valencene can be produced with this organism. In this study, systematic metabolic engineering enabled construction of a patchoulol producing C. glutamicum strain by applying the following strategies: (i construction of a farnesyl pyrophosphate-producing platform strain by combining genomic deletions with heterologous expression of ispA from Escherichia coli; (ii prevention of carotenoid-like byproduct formation; (iii overproduction of limiting enzymes from the 2-c-methyl-d-erythritol 4-phosphate (MEP-pathway to increase precursor supply; and (iv heterologous expression of the plant patchoulol synthase gene PcPS from Pogostemon cablin. Additionally, a proof of principle liter-scale fermentation with a two-phase organic overlay-culture medium system for terpenoid capture was performed. To the best of our knowledge, the patchoulol titers demonstrated here are the highest reported to date with up to 60 mg L−1 and volumetric productivities of up to 18 mg L−1 d−1.

  3. Production of L-valine from metabolically engineered Corynebacterium glutamicum.

    Science.gov (United States)

    Wang, Xiaoyuan; Zhang, Hailing; Quinn, Peter J

    2018-05-01

    L-Valine is one of the three branched-chain amino acids (valine, leucine, and isoleucine) essential for animal health and important in metabolism; therefore, it is widely added in the products of food, medicine, and feed. L-Valine is predominantly produced through microbial fermentation, and the production efficiency largely depends on the quality of microorganisms. In recent years, continuing efforts have been made in revealing the mechanisms and regulation of L-valine biosynthesis in Corynebacterium glutamicum, the most utilitarian bacterium for amino acid production. Metabolic engineering based on the metabolic biosynthesis and regulation of L-valine provides an effective alternative to the traditional breeding for strain development. Industrially competitive L-valine-producing C. glutamicum strains have been constructed by genetically defined metabolic engineering. This article reviews the global metabolic and regulatory networks responsible for L-valine biosynthesis, the molecular mechanisms of regulation, and the strategies employed in C. glutamicum strain engineering.

  4. Metabolic Engineering of Corynebacterium glutamicum for Methanol Metabolism

    Science.gov (United States)

    Witthoff, Sabrina; Schmitz, Katja; Niedenführ, Sebastian; Nöh, Katharina; Noack, Stephan

    2015-01-01

    Methanol is already an important carbon feedstock in the chemical industry, but it has found only limited application in biotechnological production processes. This can be mostly attributed to the inability of most microbial platform organisms to utilize methanol as a carbon and energy source. With the aim to turn methanol into a suitable feedstock for microbial production processes, we engineered the industrially important but nonmethylotrophic bacterium Corynebacterium glutamicum toward the utilization of methanol as an auxiliary carbon source in a sugar-based medium. Initial oxidation of methanol to formaldehyde was achieved by heterologous expression of a methanol dehydrogenase from Bacillus methanolicus, whereas assimilation of formaldehyde was realized by implementing the two key enzymes of the ribulose monophosphate pathway of Bacillus subtilis: 3-hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase. The recombinant C. glutamicum strain showed an average methanol consumption rate of 1.7 ± 0.3 mM/h (mean ± standard deviation) in a glucose-methanol medium, and the culture grew to a higher cell density than in medium without methanol. In addition, [13C]methanol-labeling experiments revealed labeling fractions of 3 to 10% in the m + 1 mass isotopomers of various intracellular metabolites. In the background of a C. glutamicum Δald ΔadhE mutant being strongly impaired in its ability to oxidize formaldehyde to CO2, the m + 1 labeling of these intermediates was increased (8 to 25%), pointing toward higher formaldehyde assimilation capabilities of this strain. The engineered C. glutamicum strains represent a promising starting point for the development of sugar-based biotechnological production processes using methanol as an auxiliary substrate. PMID:25595770

  5. Corynebacterium glutamicum for Sustainable Bioproduction: From Metabolic Physiology to Systems Metabolic Engineering.

    Science.gov (United States)

    Becker, Judith; Gießelmann, Gideon; Hoffmann, Sarah Lisa; Wittmann, Christoph

    Since its discovery 60 years ago, Corynebacterium glutamicum has evolved into a workhorse for industrial biotechnology. Traditionally well known for its remarkable capacity to produce amino acids, this Gram-positive soil bacterium, has become a flexible, efficient production platform for various bulk and fine chemicals, materials, and biofuels. The central turnstile of all these achievements is our excellent understanding of its metabolism and physiology. This knowledge base, together with innovative systems metabolic engineering concepts, which integrate systems and synthetic biology into strain engineering, has upgraded C. glutamicum into one of the most successful industrial microorganisms in the world.

  6. Complete Sucrose Metabolism Requires Fructose Phosphotransferase Activity in Corynebacterium glutamicum To Ensure Phosphorylation of Liberated Fructose

    OpenAIRE

    Dominguez, H.; Lindley, N. D.

    1996-01-01

    Sucrose uptake by Corynebacterium glutamicum involves a phosphoenolpyruvate-dependent sucrose phosphotransferase (PTS), but in the absence of fructokinase, further metabolism of the liberated fructose requires efflux of the fructose and reassimilation via the fructose PTS. Mutant strains lacking detectable fructose-transporting PTS activity accumulated fructose extracellularly but consumed sucrose at rates comparable to those of the wild-type strain.

  7. Metabolic evolution and a comparative omics analysis of Corynebacterium glutamicum for putrescine production.

    Science.gov (United States)

    Li, Zhen; Shen, Yu-Ping; Jiang, Xuan-Long; Feng, Li-Shen; Liu, Jian-Zhong

    2018-02-01

    Putrescine is widely used in the industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Because the highest titer of putrescine is much lower than that of its precursor L-ornithine reported in microorganisms to date, further work is needed to increase putrescine production in Corynebacterium glutamicum. We first compared 7 ornithine decarboxylase genes and found that the Enterobacter cloacae ornithine decarboxylase gene speC1 was most suitable for putrescine production in C. glutamicum. Increasing NADPH availability and blocking putrescine oxidation and acetylation were chosen as targets for metabolic engineering. The putrescine producer C. glutamicum PUT4 was first constructed by deleting puo, butA and snaA genes, and replacing the fabG gene with E. cloacae speC1. After adaptive evolution with C. glutamicum PUT4, the evolved strain C. glutamicum PUT-ALE, which produced an 96% higher amount of putrescine compared to the parent strain, was obtained. The whole genome resequencing indicates that the SNPs located in the odhA coding region may be associated with putrescine production. The comparative proteomic analysis reveals that the pentose phosphate and anaplerotic pathway, the glyoxylate cycle, and the ornithine biosynthetic pathway were upregulated in the evolved strain C. glutamicum PUT-ALE. The aspartate family, aromatic, and branched chain amino acid and fatty acid biosynthetic pathways were also observed to be downregulated in C. glutamicum PUT-ALE. Reducing OdhA activity by replacing the odhA native start codon GTG with TTG and overexpression of cgmA or pyc458 further improved putrescine production. Repressing the carB, ilvH, ilvB and aroE expression via CRISPRi also increased putrescine production by 5, 9, 16 and 19%, respectively.

  8. In Silico Genome-Scale Reconstruction and Validation of the Corynebacterium glutamicum Metabolic Network

    DEFF Research Database (Denmark)

    Kjeldsen, Kjeld Raunkjær; Nielsen, J.

    2009-01-01

    A genome-scale metabolic model of the Gram-positive bacteria Corynebacterium glutamicum ATCC 13032 was constructed comprising 446 reactions and 411 metabolite, based on the annotated genome and available biochemical information. The network was analyzed using constraint based methods. The model...... was extensively validated against published flux data, and flux distribution values were found to correlate well between simulations and experiments. The split pathway of the lysine synthesis pathway of C. glutamicum was investigated, and it was found that the direct dehydrogenase variant gave a higher lysine...... yield than the alternative succinyl pathway at high lysine production rates. The NADPH demand of the network was not found to be critical for lysine production until lysine yields exceeded 55% (mmol lysine (mmol glucose)(-1)). The model was validated during growth on the organic acids acetate...

  9. Metabolic engineering of Corynebacterium glutamicum aimed at alternative carbon sources and new products

    Directory of Open Access Journals (Sweden)

    Volker Fritz Wendisch

    2012-10-01

    Full Text Available Corynebacterium glutamicum is well known as the amino acid-producing workhorse of fermentation industry, being used for multi-million-ton scale production of glutamate and lysine for more than 60 years. However, it is only recently that extensive research has focused on engineering it beyond the scope of amino acids. Meanwhile, a variety of corynebacterial strains allows access to alternative carbon sources and/or allows production of a wide range of industrially relevant compounds. Some of these efforts set new standards in terms of titers and productivities achieved whereas others represent a proof-of-principle. These achievements manifest the position of C. glutamicum as an important industrial microorganism with capabilities far beyond the traditional amino acid production. In this review we focus on the state of the art of metabolic engineering of C. glutamicum for utilization of alternative carbon sources, (e.g. coming from wastes and unprocessed sources, and construction of C. glutamicum strains for production of new products such as diamines, organic acids and alcohols.

  10. CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum.

    Science.gov (United States)

    Cho, Jae Sung; Choi, Kyeong Rok; Prabowo, Cindy Pricilia Surya; Shin, Jae Ho; Yang, Dongsoo; Jang, Jaedong; Lee, Sang Yup

    2017-07-01

    Genome engineering of Corynebacterium glutamicum, an important industrial microorganism for amino acids production, currently relies on random mutagenesis and inefficient double crossover events. Here we report a rapid genome engineering strategy to scarlessly knock out one or more genes in C. glutamicum in sequential and iterative manner. Recombinase RecT is used to incorporate synthetic single-stranded oligodeoxyribonucleotides into the genome and CRISPR/Cas9 to counter-select negative mutants. We completed the system by engineering the respective plasmids harboring CRISPR/Cas9 and RecT for efficient curing such that multiple gene targets can be done iteratively and final strains will be free of plasmids. To demonstrate the system, seven different mutants were constructed within two weeks to study the combinatorial deletion effects of three different genes on the production of γ-aminobutyric acid, an industrially relevant chemical of much interest. This genome engineering strategy will expedite metabolic engineering of C. glutamicum. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  11. Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Zhen Li

    2017-10-01

    Full Text Available Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6, metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production.

  12. Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

    Science.gov (United States)

    Li, Zhen; Liu, Jian-Zhong

    2017-01-01

    Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6), metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production. PMID:29089930

  13. Metabolic engineering of Corynebacterium glutamicum to produce GDP-L-fucose from glucose and mannose.

    Science.gov (United States)

    Chin, Young-Wook; Park, Jin-Byung; Park, Yong-Cheol; Kim, Kyoung Heon; Seo, Jin-Ho

    2013-06-01

    Wild-type Corynebacterium glutamicum was metabolically engineered to convert glucose and mannose into guanosine 5'-diphosphate (GDP)-L-fucose, a precursor of fucosyl-oligosaccharides, which are involved in various biological and pathological functions. This was done by introducing the gmd and wcaG genes of Escherichia coli encoding GDP-D-mannose-4,6-dehydratase and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase, respectively, which are known as key enzymes in the production of GDP-L-fucose from GDP-D-mannose. Coexpression of the genes allowed the recombinant C. glutamicum cells to produce GDP-L-fucose in a minimal medium containing glucose and mannose as carbon sources. The specific product formation rate was much higher during growth on mannose than on glucose. In addition, the specific product formation rate was further increased by coexpressing the endogenous phosphomanno-mutase gene (manB) and GTP-mannose-1-phosphate guanylyl-transferase gene (manC), which are involved in the conversion of mannose-6-phosphate into GDP-D-mannose. However, the overexpression of manA encoding mannose-6-phosphate isomerase, catalyzing interconversion of mannose-6-phosphate and fructose-6-phosphate showed a negative effect on formation of the target product. Overall, coexpression of gmd, wcaG, manB and manC in C. glutamicum enabled production of GDP-L-fucose at the specific rate of 0.11 mg g cell(-1) h(-1). The specific GDP-L-fucose content reached 5.5 mg g cell(-1), which is a 2.4-fold higher than that of the recombinant E. coli overexpressing gmd, wcaG, manB and manC under comparable conditions. Well-established metabolic engineering tools may permit optimization of the carbon and cofactor metabolisms of C. glutamicum to further improve their production capacity.

  14. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

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    Wittmann Christoph

    2008-03-01

    Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

  15. Systems metabolic engineering of Corynebacterium glutamicum for production of the chemical chaperone ectoine.

    Science.gov (United States)

    Becker, Judith; Schäfer, Rudolf; Kohlstedt, Michael; Harder, Björn J; Borchert, Nicole S; Stöveken, Nadine; Bremer, Erhard; Wittmann, Christoph

    2013-11-15

    The stabilizing and function-preserving effects of ectoines have attracted considerable biotechnological interest up to industrial scale processes for their production. These rely on the release of ectoines from high-salinity-cultivated microbial producer cells upon an osmotic down-shock in rather complex processor configurations. There is growing interest in uncoupling the production of ectoines from the typical conditions required for their synthesis, and instead design strains that naturally release ectoines into the medium without the need for osmotic changes, since the use of high-salinity media in the fermentation process imposes notable constraints on the costs, design, and durability of fermenter systems. Here, we used a Corynebacterium glutamicum strain as a cellular chassis to establish a microbial cell factory for the biotechnological production of ectoines. The implementation of a mutant aspartokinase enzyme ensured efficient supply of L-aspartate-beta-semialdehyde, the precursor for ectoine biosynthesis. We further engineered the genome of the basic C. glutamicum strain by integrating a codon-optimized synthetic ectABCD gene cluster under expressional control of the strong and constitutive C. glutamicum tuf promoter. The resulting recombinant strain produced ectoine and excreted it into the medium; however, lysine was still found as a by-product. Subsequent inactivation of the L-lysine exporter prevented the undesired excretion of lysine while ectoine was still exported. Using the streamlined cell factory, a fed-batch process was established that allowed the production of ectoine with an overall productivity of 6.7 g L(-1) day(-1) under growth conditions that did not rely on the use of high-salinity media. The present study describes the construction of a stable microbial cell factory for recombinant production of ectoine. We successfully applied metabolic engineering strategies to optimize its synthetic production in the industrial workhorse C

  16. Metabolic engineering of Corynebacterium glutamicum for fermentative production of chemicals in biorefinery.

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    Baritugo, Kei-Anne; Kim, Hee Taek; David, Yokimiko; Choi, Jong-Il; Hong, Soon Ho; Jeong, Ki Jun; Choi, Jong Hyun; Joo, Jeong Chan; Park, Si Jae

    2018-05-01

    Bio-based production of industrially important chemicals provides an eco-friendly alternative to current petrochemical-based processes. Because of the limited supply of fossil fuel reserves, various technologies utilizing microbial host strains for the sustainable production of platform chemicals from renewable biomass have been developed. Corynebacterium glutamicum is a non-pathogenic industrial microbial species traditionally used for L-glutamate and L-lysine production. It is a promising species for industrial production of bio-based chemicals because of its flexible metabolism that allows the utilization of a broad spectrum of carbon sources and the production of various amino acids. Classical breeding, systems, synthetic biology, and metabolic engineering approaches have been used to improve its applications, ranging from traditional amino-acid production to modern biorefinery systems for production of value-added platform chemicals. This review describes recent advances in the development of genetic engineering tools and techniques for the establishment and optimization of metabolic pathways for bio-based production of major C2-C6 platform chemicals using recombinant C. glutamicum.

  17. Metabolic engineering of the L-valine biosynthesis pathway in Corynebacterium glutamicum using promoter activity modulation

    Czech Academy of Sciences Publication Activity Database

    Holátko, Jiří; Elišáková, Veronika; Prouza, Marek; Sobotka, Miroslav; Nešvera, Jan; Pátek, Miroslav

    2009-01-01

    Roč. 139, č. 3 (2009), s. 203-210 ISSN 0168-1656 R&D Projects: GA ČR GA204/06/0330 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * valine production * promoters Subject RIV: EE - Microbiology, Virology Impact factor: 2.881, year: 2009

  18. Systems-wide metabolic pathway engineering in Corynebacterium glutamicum for bio-based production of diaminopentane.

    Science.gov (United States)

    Kind, Stefanie; Jeong, Weol Kyu; Schröder, Hartwig; Wittmann, Christoph

    2010-07-01

    In the present work the Gram-positive bacterium Corynebacterium glutamicum was engineered into an efficient, tailor-made production strain for diaminopentane (cadaverine), a highly attractive building block for bio-based polyamides. The engineering comprised expression of lysine decarboxylase (ldcC) from Escherichia coli, catalyzing the conversion of lysine into diaminopentane, and systems-wide metabolic engineering of central supporting pathways. Substantially re-designing the metabolism yielded superior strains with desirable properties such as (i) the release from unwanted feedback regulation at the level of aspartokinase and pyruvate carboxylase by introducing the point mutations lysC311 and pycA458, (ii) an optimized supply of the key precursor oxaloacetate by amplifying the anaplerotic enzyme, pyruvate carboxylase, and deleting phosphoenolpyruvate carboxykinase which otherwise removes oxaloacetate, (iii) enhanced biosynthetic flux via combined amplification of aspartokinase, dihydrodipicolinate reductase, diaminopimelate dehydrogenase and diaminopimelate decarboxylase, and (iv) attenuated flux into the threonine pathway competing with production by the leaky mutation hom59 in the homoserine dehydrogenase gene. Lysine decarboxylase proved to be a bottleneck for efficient production, since its in vitro activity and in vivo flux were closely correlated. To achieve an optimal strain having only stable genomic modifications, the combination of the strong constitutive C. glutamicum tuf promoter and optimized codon usage allowed efficient genome-based ldcC expression and resulted in a high diaminopentane yield of 200 mmol mol(-1). By supplementing the medium with 1 mgL(-1) pyridoxal, the cofactor of lysine decarboxylase, the yield was increased to 300 mmol mol(-1). In the production strain obtained, lysine secretion was almost completely abolished. Metabolic analysis, however, revealed substantial formation of an as yet unknown by-product. It was identified as an

  19. Recent advances in the metabolic engineering of Corynebacterium glutamicum for the production of lactate and succinate from renewable resources.

    Science.gov (United States)

    Tsuge, Yota; Hasunuma, Tomohisa; Kondo, Akihiko

    2015-03-01

    Recent increasing attention to environmental issues and the shortage of oil resources have spurred political and industrial interest in the development of environmental friendly and cost-effective processes for the production of bio-based chemicals from renewable resources. Thus, microbial production of commercially important chemicals is viewed as a desirable way to replace current petrochemical production. Corynebacterium glutamicum, a Gram-positive soil bacterium, is one of the most important industrial microorganisms as a platform for the production of various amino acids. Recent research has explored the use of C. glutamicum as a potential cell factory for producing organic acids such as lactate and succinate, both of which are commercially important bulk chemicals. Here, we summarize current understanding in this field and recent metabolic engineering efforts to develop C. glutamicum strains that efficiently produce L- and D-lactate, and succinate from renewable resources.

  20. Rational Design of a Corynebacterium glutamicum Pantothenate Production Strain and Ins Characterization by Metabolic Flux Analysis and Genome-Wide Transcriptional Profiling

    Czech Academy of Sciences Publication Activity Database

    Hüser, A.T.; Chassagnole, Ch.; Lindley, N.D.; Merkamm, M.; Guyonvarch, A.; Elišáková, Veronika; Pátek, Miroslav; Kalinowski, J.; Brune, I.; Pühler, A.; Tauch, A.

    2005-01-01

    Roč. 71, č. 6 (2005), s. 3255-3268 ISSN 0099-2240 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * metabolic flux Subject RIV: EE - Microbiology, Virology Impact factor: 3.818, year: 2005

  1. C1 Metabolism in Corynebacterium glutamicum: an Endogenous Pathway for Oxidation of Methanol to Carbon Dioxide

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    Witthoff, Sabrina; Mühlroth, Alice

    2013-01-01

    Methanol is considered an interesting carbon source in “bio-based” microbial production processes. Since Corynebacterium glutamicum is an important host in industrial biotechnology, in particular for amino acid production, we performed studies of the response of this organism to methanol. The C. glutamicum wild type was able to convert 13C-labeled methanol to 13CO2. Analysis of global gene expression in the presence of methanol revealed several genes of ethanol catabolism to be upregulated, indicating that some of the corresponding enzymes are involved in methanol oxidation. Indeed, a mutant lacking the alcohol dehydrogenase gene adhA showed a 62% reduced methanol consumption rate, indicating that AdhA is mainly responsible for methanol oxidation to formaldehyde. Further studies revealed that oxidation of formaldehyde to formate is catalyzed predominantly by two enzymes, the acetaldehyde dehydrogenase Ald and the mycothiol-dependent formaldehyde dehydrogenase AdhE. The Δald ΔadhE and Δald ΔmshC deletion mutants were severely impaired in their ability to oxidize formaldehyde, but residual methanol oxidation to CO2 was still possible. The oxidation of formate to CO2 is catalyzed by the formate dehydrogenase FdhF, recently identified by us. Similar to the case with ethanol, methanol catabolism is subject to carbon catabolite repression in the presence of glucose and is dependent on the transcriptional regulator RamA, which was previously shown to be essential for expression of adhA and ald. In conclusion, we were able to show that C. glutamicum possesses an endogenous pathway for methanol oxidation to CO2 and to identify the enzymes and a transcriptional regulator involved in this pathway. PMID:24014532

  2. Reprogramming One-Carbon Metabolic Pathways To Decouple l-Serine Catabolism from Cell Growth in Corynebacterium glutamicum.

    Science.gov (United States)

    Zhang, Yun; Shang, Xiuling; Lai, Shujuan; Zhang, Yu; Hu, Qitiao; Chai, Xin; Wang, Bo; Liu, Shuwen; Wen, Tingyi

    2018-02-16

    l-Serine, the principal one-carbon source for DNA biosynthesis, is difficult for microorganisms to accumulate due to the coupling of l-serine catabolism and microbial growth. Here, we reprogrammed the one-carbon unit metabolic pathways in Corynebacterium glutamicum to decouple l-serine catabolism from cell growth. In silico model-based simulation showed a negative influence on glyA-encoding serine hydroxymethyltransferase flux with l-serine productivity. Attenuation of glyA transcription resulted in increased l-serine accumulation, and a decrease in purine pools, poor growth and longer cell shapes. The gcvTHP-encoded glycine cleavage (Gcv) system from Escherichia coli was introduced into C. glutamicum, allowing glycine-derived 13 CH 2 to be assimilated into intracellular purine synthesis, which resulted in an increased amount of one-carbon units. Gcv introduction not only restored cell viability and morphology but also increased l-serine accumulation. Moreover, comparative proteomic analysis indicated that abundance changes of the enzymes involved in one-carbon unit cycles might be responsible for maintaining one-carbon unit homeostasis. Reprogramming of the one-carbon metabolic pathways allowed cells to reach a comparable growth rate to accumulate 13.21 g/L l-serine by fed-batch fermentation in minimal medium. This novel strategy provides new insights into the regulation of cellular properties and essential metabolite accumulation by introducing an extrinsic pathway.

  3. Metabolic Design of Corynebacterium glutamicum for Production of l-Cysteine with Consideration of Sulfur-Supplemented Animal Feed.

    Science.gov (United States)

    Joo, Young-Chul; Hyeon, Jeong Eun; Han, Sung Ok

    2017-06-14

    l-Cysteine is a valuable sulfur-containing amino acid widely used as a nutrition supplement in industrial food production, agriculture, and animal feed. However, this amino acid is mostly produced by acid hydrolysis and extraction from human or animal hairs. In this study, we constructed recombinant Corynebacterium glutamicum strains that overexpress combinatorial genes for l-cysteine production. The aims of this work were to investigate the effect of the combined overexpression of serine acetyltransferase (CysE), O-acetylserine sulfhydrylase (CysK), and the transcriptional regulator CysR on l-cysteine production. The CysR-overexpressing strain accumulated approximately 2.7-fold more intracellular sulfide than the control strain (empty pMT-tac vector). Moreover, in the resulting CysEKR recombinant strain, combinatorial overexpression of genes involved in l-cysteine production successfully enhanced its production by approximately 3.0-fold relative to that in the control strain. This study demonstrates a biotechnological model for the production of animal feed supplements such as l-cysteine using metabolically engineered C. glutamicum.

  4. Sigma factors and promoters in Corynebacterium glutamicum

    Czech Academy of Sciences Publication Activity Database

    Pátek, Miroslav; Nešvera, Jan

    2011-01-01

    Roč. 154, 2-3 (2011), s. 101-113 ISSN 0168-1656 R&D Projects: GA ČR GC204/09/J015 Institutional research plan: CEZ:AV0Z50200510 Keywords : Corynebacterium glutamicum * Sigma factors * Promoters Subject RIV: EE - Microbiology, Virology Impact factor: 3.045, year: 2011

  5. Overexpression of Genes Encoding Glycolytic Enzymes in Corynebacterium glutamicum Enhances Glucose Metabolism and Alanine Production under Oxygen Deprivation Conditions

    Science.gov (United States)

    Yamamoto, Shogo; Gunji, Wataru; Suzuki, Hiroaki; Toda, Hiroshi; Suda, Masako; Jojima, Toru; Inui, Masayuki

    2012-01-01

    We previously reported that Corynebacterium glutamicum strain ΔldhAΔppc+alaD+gapA, overexpressing glyceraldehyde-3-phosphate dehydrogenase-encoding gapA, shows significantly improved glucose consumption and alanine formation under oxygen deprivation conditions (T. Jojima, M. Fujii, E. Mori, M. Inui, and H. Yukawa, Appl. Microbiol. Biotechnol. 87:159–165, 2010). In this study, we employ stepwise overexpression and chromosomal integration of a total of four genes encoding glycolytic enzymes (herein referred to as glycolytic genes) to demonstrate further successive improvements in C. glutamicum glucose metabolism under oxygen deprivation. In addition to gapA, overexpressing pyruvate kinase-encoding pyk and phosphofructokinase-encoding pfk enabled strain GLY2/pCRD500 to realize respective 13% and 20% improved rates of glucose consumption and alanine formation compared to GLY1/pCRD500. Subsequent overexpression of glucose-6-phosphate isomerase-encoding gpi in strain GLY3/pCRD500 further improved its glucose metabolism. Notably, both alanine productivity and yield increased after each overexpression step. After 48 h of incubation, GLY3/pCRD500 produced 2,430 mM alanine at a yield of 91.8%. This was 6.4-fold higher productivity than that of the wild-type strain. Intracellular metabolite analysis showed that gapA overexpression led to a decreased concentration of metabolites upstream of glyceraldehyde-3-phosphate dehydrogenase, suggesting that the overexpression resolved a bottleneck in glycolysis. Changing ratios of the extracellular metabolites by overexpression of glycolytic genes resulted in reduction of the intracellular NADH/NAD+ ratio, which also plays an important role on the improvement of glucose consumption. Enhanced alanine dehydrogenase activity using a high-copy-number plasmid further accelerated the overall alanine productivity. Increase in glycolytic enzyme activities is a promising approach to make drastic progress in growth-arrested bioprocesses. PMID

  6. Transcriptome and Gene Ontology (GO) Enrichment Analysis Reveals Genes Involved in Biotin Metabolism That Affect L-Lysine Production in Corynebacterium glutamicum.

    Science.gov (United States)

    Kim, Hong-Il; Kim, Jong-Hyeon; Park, Young-Jin

    2016-03-09

    Corynebacterium glutamicum is widely used for amino acid production. In the present study, 543 genes showed a significant change in their mRNA expression levels in L-lysine-producing C. glutamicum ATCC21300 than that in the wild-type C. glutamicum ATCC13032. Among these 543 differentially expressed genes (DEGs), 28 genes were up- or downregulated. In addition, 454 DEGs were functionally enriched and categorized based on BLAST sequence homologies and gene ontology (GO) annotations using the Blast2GO software. Interestingly, NCgl0071 (bioB, encoding biotin synthase) was expressed at levels ~20-fold higher in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain. Five other genes involved in biotin metabolism or transport--NCgl2515 (bioA, encoding adenosylmethionine-8-amino-7-oxononanoate aminotransferase), NCgl2516 (bioD, encoding dithiobiotin synthetase), NCgl1883, NCgl1884, and NCgl1885--were also expressed at significantly higher levels in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain, which we determined using both next-generation RNA sequencing and quantitative real-time PCR analysis. When we disrupted the bioB gene in C. glutamicum ATCC21300, L-lysine production decreased by approximately 76%, and the three genes involved in biotin transport (NCgl1883, NCgl1884, and NCgl1885) were significantly downregulated. These results will be helpful to improve our understanding of C. glutamicum for industrial amino acid production.

  7. Synthetic promoter libraries for Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Rytter, Jakob Vang; Helmark, Søren; Chen, Jun

    2014-01-01

    The ability to modulate gene expression is an important genetic tool in systems biology and biotechnology. Here, we demonstrate that a previously published easy and fast PCR-based method for modulating gene expression in lactic acid bacteria is also applicable to Corynebacterium glutamicum. We co...... promoter library (SPL) technology is convenient for modulating gene expression in C. glutamicum and should have many future applications, within basic research as well as for optimizing industrial production organisms....... constructed constitutive promoter libraries based on various combinations of a previously reported C. glutamicum -10 consensus sequence (gngnTA(c/t)aaTgg) and the Escherichia coli -35 consensus, either with or without an AT-rich region upstream. A promoter library based on consensus sequences frequently found...... in low-GC Gram-positive microorganisms was also included. The strongest promoters were found in the library with a -35 region and a C. glutamicum -10 consensus, and this library also represents the largest activity span. Using the alternative -10 consensus TATAAT, which can be found in many other...

  8. Metabolic flux distributions in Corynebacterium glutamicum during growth and lysine overproduction. Reprinted from Biotechnology and Bioengineering, Vol. 41, Pp 633-646 (1993).

    Science.gov (United States)

    Vallino, J J; Stephanopoulos, G

    2000-03-20

    The two main contributions of this article are the solidification of Corynebacterium glutamicum biochemistry guided by bioreaction network analysis, and the determination of basal metabolic flux distributions during growth and lysine synthesis. Employed methodology makes use of stoichiometrically based mass balances to determine flux distributions in the C. glutamicum metabolic network. Presented are a brief description of the methodology, a thorough literature review of glutamic acid bacteria biochemistry, and specific results obtained through a combination of fermentation studies and analysis-directed intracellular assays. The latter include the findings of the lack of activity of glyoxylate shunt, and that phosphoenolpyruvate carboxylase (PPC) is the only anaplerotic reaction expressed in C. glutamicum cultivated on glucose minimal media. Network simplifications afforded by the above findings facilitated the determination of metabolic flux distributions under a variety of culture conditions and led to the following conclusions. Both the pentose phosphate pathway and PPC support significant fluxes during growth and lysine overproduction, and that flux partitioning at the glucosa-6-phosphate branch point does not appear to limit lysine synthesis. Copyright 1993 John Wiley & Sons, Inc.

  9. Functional characterization of a vanillin dehydrogenase in Corynebacterium glutamicum

    Science.gov (United States)

    Ding, Wei; Si, Meiru; Zhang, Weipeng; Zhang, Yaoling; Chen, Can; Zhang, Lei; Lu, Zhiqiang; Chen, Shaolin; Shen, Xihui

    2015-01-01

    Vanillin dehydrogenase (VDH) is a crucial enzyme involved in the degradation of lignin-derived aromatic compounds. Herein, the VDH from Corynebacterium glutamicum was characterized. The relative molecular mass (Mr) determined by SDS-PAGE was ~51kDa, whereas the apparent native Mr values revealed by gel filtration chromatography were 49.5, 92.3, 159.0 and 199.2kDa, indicating the presence of dimeric, trimeric and tetrameric forms. Moreover, the enzyme showed its highest level of activity toward vanillin at pH 7.0 and 30C, and interestingly, it could utilize NAD+ and NADP+ as coenzymes with similar efficiency and showed no obvious difference toward NAD+ and NADP+. In addition to vanillin, this enzyme exhibited catalytic activity toward a broad range of substrates, including p-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, o-phthaldialdehyde, cinnamaldehyde, syringaldehyde and benzaldehyde. Conserved catalytic residues or putative cofactor interactive sites were identified based on sequence alignment and comparison with previous studies, and the function of selected residues were verified by site-directed mutagenesis analysis. Finally, the vdh deletion mutant partially lost its ability to grow on vanillin, indicating the presence of alternative VDH(s) in Corynebacterium glutamicum. Taken together, this study contributes to understanding the VDH diversity from bacteria and the aromatic metabolism pathways in C. glutamicum. PMID:25622822

  10. A Novel Corynebacterium glutamicum l-Glutamate Exporter.

    Science.gov (United States)

    Wang, Yu; Cao, Guoqiang; Xu, Deyu; Fan, Liwen; Wu, Xinyang; Ni, Xiaomeng; Zhao, Shuxin; Zheng, Ping; Sun, Jibin; Ma, Yanhe

    2018-03-15

    Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to

  11. A role of the transcriptional regulator LldR (NCgl2814) in glutamate metabolism under biotin-limited conditions in Corynebacterium glutamicum.

    Science.gov (United States)

    Supkulsutra, Tanyanut; Maeda, Tomoya; Kumagai, Kosuke; Wachi, Masaaki

    2013-01-01

    Corynebacterium glutamicum is a Gram-positive, rod-shaped, aerobic bacterium used for the fermentative production of L-glutamate. LldR (NCgl2814) is known as a repressor for ldhA and lldD encoding lactate dehydrogenases. LdhA is responsible for production of L-lactate, while LldD is for its assimilation. Since L-lactate production was observed as a by-product of glutamate production under biotin-limited conditions, LldR might play a regulatory role in the glutamate metabolism. Here for the first time, we investigated effects of overproduction or deletion of LldR on the glutamate metabolism under biotin-limited conditions in C. glutamicum. It was found that glutamate production under biotin-limited conditions was decreased by overproduction of LldR. In the wild-type cells, L-lactate was produced in the first 24 h and it was re-consumed thereafter. On the other hand, in the overproduced cells, L-lactate was produced like the wild type, but it was not re-consumed. This means that L-lactate assimilation, which is catalyzed by LldD, was suppressed by the overproduction of LldR, but L-lactate production, which is catalyzed by LdhA, was not affected, indicating that LldR mainly controls the expression of lldD but not of ldhA under biotin-limited conditions. This was confirmed by quantitative real-time RT-PCR. From these results, it is suggested that L-lactate metabolism, which is controlled by LldR, has a buffering function of the pyruvate pool for glutamate production.

  12. Metabolome analysis-based design and engineering of a metabolic pathway in Corynebacterium glutamicum to match rates of simultaneous utilization of D-glucose and L-arabinose.

    Science.gov (United States)

    Kawaguchi, Hideo; Yoshihara, Kumiko; Hara, Kiyotaka Y; Hasunuma, Tomohisa; Ogino, Chiaki; Kondo, Akihiko

    2018-05-17

    L-Arabinose is the second most abundant component of hemicellulose in lignocellulosic biomass, next to D-xylose. However, few microorganisms are capable of utilizing pentoses, and catabolic genes and operons enabling bacterial utilization of pentoses are typically subject to carbon catabolite repression by more-preferred carbon sources, such as D-glucose, leading to a preferential utilization of D-glucose over pentoses. In order to simultaneously utilize both D-glucose and L-arabinose at the same rate, a modified metabolic pathway was rationally designed based on metabolome analysis. Corynebacterium glutamicum ATCC 31831 utilized D-glucose and L-arabinose simultaneously at a low concentration (3.6 g/L each) but preferentially utilized D-glucose over L-arabinose at a high concentration (15 g/L each), although L-arabinose and D-glucose were consumed at comparable rates in the absence of the second carbon source. Metabolome analysis revealed that phosphofructokinase and pyruvate kinase were major bottlenecks for D-glucose and L-arabinose metabolism, respectively. Based on the results of metabolome analysis, a metabolic pathway was engineered by overexpressing pyruvate kinase in combination with deletion of araR, which encodes a repressor of L-arabinose uptake and catabolism. The recombinant strain utilized high concentrations of D-glucose and L-arabinose (15 g/L each) at the same consumption rate. During simultaneous utilization of both carbon sources at high concentrations, intracellular levels of phosphoenolpyruvate declined and acetyl-CoA levels increased significantly as compared with the wild-type strain that preferentially utilized D-glucose. These results suggest that overexpression of pyruvate kinase in the araR deletion strain increased the specific consumption rate of L-arabinose and that citrate synthase activity becomes a new bottleneck in the engineered pathway during the simultaneous utilization of D-glucose and L-arabinose. Metabolome analysis

  13. Tools for genetic manipulations in Corynebacterium glutamicum and their applications

    Czech Academy of Sciences Publication Activity Database

    Nešvera, Jan; Pátek, Miroslav

    2011-01-01

    Roč. 90, č. 5 (2011), s. 1641-1654 ISSN 0175-7598 R&D Projects: GA ČR GC204/09/J015 Institutional research plan: CEZ:AV0Z50200510 Keywords : Corynebacterium glutamicum * Plasmid vectors * Promoters Subject RIV: EE - Microbiology, Virology Impact factor: 3.425, year: 2011

  14. Transcriptome and Multivariable Data Analysis of Corynebacterium glutamicum under Different Dissolved Oxygen Conditions in Bioreactors

    Science.gov (United States)

    Sun, Yang; Guo, Wenwen; Wang, Fen; Peng, Feng; Yang, Yankun; Dai, Xiaofeng; Liu, Xiuxia; Bai, Zhonghu

    2016-01-01

    Dissolved oxygen (DO) is an important factor in the fermentation process of Corynebacterium glutamicum, which is a widely used aerobic microbe in bio-industry. Herein, we described RNA-seq for C. glutamicum under different DO levels (50%, 30% and 0%) in 5 L bioreactors. Multivariate data analysis (MVDA) models were used to analyze the RNA-seq and metabolism data to investigate the global effect of DO on the transcriptional distinction of the substance and energy metabolism of C. glutamicum. The results showed that there were 39 and 236 differentially expressed genes (DEGs) under the 50% and 0% DO conditions, respectively, compared to the 30% DO condition. Key genes and pathways affected by DO were analyzed, and the result of the MVDA and RNA-seq revealed that different DO levels in the fermenter had large effects on the substance and energy metabolism and cellular redox balance of C. glutamicum. At low DO, the glycolysis pathway was up-regulated, and TCA was shunted by the up-regulation of the glyoxylate pathway and over-production of amino acids, including valine, cysteine and arginine. Due to the lack of electron-acceptor oxygen, 7 genes related to the electron transfer chain were changed, causing changes in the intracellular ATP content at 0% and 30% DO. The metabolic flux was changed to rebalance the cellular redox. This study applied deep sequencing to identify a wealth of genes and pathways that changed under different DO conditions and provided an overall comprehensive view of the metabolism of C. glutamicum. The results provide potential ways to improve the oxygen tolerance of C. glutamicum and to modify the metabolic flux for amino acid production and heterologous protein expression. PMID:27907077

  15. Metabolic engineering of an ATP-neutral Embden-Meyerhof-Parnas pathway in Corynebacterium glutamicum: growth restoration by an adaptive point mutation in NADH dehydrogenase.

    Science.gov (United States)

    Komati Reddy, Gajendar; Lindner, Steffen N; Wendisch, Volker F

    2015-03-01

    Corynebacterium glutamicum uses the Embden-Meyerhof-Parnas pathway of glycolysis and gains 2 mol of ATP per mol of glucose by substrate-level phosphorylation (SLP). To engineer glycolysis without net ATP formation by SLP, endogenous phosphorylating NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was replaced by nonphosphorylating NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (GapN) from Clostridium acetobutylicum, which irreversibly converts glyceraldehyde-3-phosphate (GAP) to 3-phosphoglycerate (3-PG) without generating ATP. As shown recently (S. Takeno, R. Murata, R. Kobayashi, S. Mitsuhashi, and M. Ikeda, Appl Environ Microbiol 76:7154-7160, 2010, http://dx.doi.org/10.1128/AEM.01464-10), this ATP-neutral, NADPH-generating glycolytic pathway did not allow for the growth of Corynebacterium glutamicum with glucose as the sole carbon source unless hitherto unknown suppressor mutations occurred; however, these mutations were not disclosed. In the present study, a suppressor mutation was identified, and it was shown that heterologous expression of udhA encoding soluble transhydrogenase from Escherichia coli partly restored growth, suggesting that growth was inhibited by NADPH accumulation. Moreover, genome sequence analysis of second-site suppressor mutants that were able to grow faster with glucose revealed a single point mutation in the gene of non-proton-pumping NADH:ubiquinone oxidoreductase (NDH-II) leading to the amino acid change D213G, which was shared by these suppressor mutants. Since related NDH-II enzymes accepting NADPH as the substrate possess asparagine or glutamine residues at this position, D213G, D213N, and D213Q variants of C. glutamicum NDH-II were constructed and were shown to oxidize NADPH in addition to NADH. Taking these findings together, ATP-neutral glycolysis by the replacement of endogenous NAD-dependent GAPDH with NADP-dependent GapN became possible via oxidation of NADPH formed in this pathway by mutant NADPH

  16. Alterations in the transcription factors GntR1 and RamA enhance the growth and central metabolism of Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Wang, Zhihao; Liu, Jianming; Chen, Lin

    2018-01-01

    confirmed that the two mutations lead to alteration rather than elimination of function, and their introduction in the wild-type background resulted in a specific growth rate of 0.62h-1. The glycolytic and pentose phosphate pathway fluxes had both increased significantly, and a transcriptomic analyses......% improvement is the highest reported for C. glutamicum to date. By genome resequencing and inverse metabolic engineering, we were able to pinpoint two mutations contributing to most of the growth improvement, and these resided in the transcriptional regulators GntR1 (gntR1-E70K) and RamA (ramA-A52V). We...... was already fast. We also found that the mutations could improve the performance of resting cells, under oxygen-deprived conditions, where an increase in sugar consumption rate of around 30% could be achieved. In conclusion, we have demonstrated that it is feasible to reprogram C. glutamicum into growing...

  17. Expression, crystallization and preliminary crystallographic study of GluB from Corynebacterium glutamicum

    International Nuclear Information System (INIS)

    Liu, Qingbo; Li, Defeng; Hu, Yonglin; Wang, Da-Cheng

    2013-01-01

    GluB, a substrate-binding protein from C. glutamicum, was expressed, purified and crystallized, followed by X-ray diffraction data collection and preliminary crystallographic analysis. GluB is a substrate-binding protein (SBP) which participates in the uptake of glutamic acid in Corynebacterium glutamicum, a Gram-positive bacterium. It is part of an ATP-binding cassette (ABC) transporter system. Together with the transmembrane proteins GluC and GluD and the cytoplasmic protein GluA, which couples the hydrolysis of ATP to the translocation of glutamate, they form a highly active glutamate-uptake system. As part of efforts to study the amino-acid metabolism, especially the metabolism of glutamic acid by C. glutamicum, a bacterium that is widely used in the industrial production of glutamic acid, the GluB protein was expressed, purified and crystallized, an X-ray diffraction data set was collected to a resolution of 1.9 Å and preliminary crystallographic analysis was performed. The crystal belonged to space group P3 1 21 or P3 2 21, with unit-cell parameters a = b = 82.50, c = 72.69 Å

  18. The flexible feedstock concept in Industrial Biotechnology: Metabolic engineering of Escherichia coli, Corynebacterium glutamicum, Pseudomonas, Bacillus and yeast strains for access to alternative carbon sources.

    Science.gov (United States)

    Wendisch, Volker F; Brito, Luciana Fernandes; Gil Lopez, Marina; Hennig, Guido; Pfeifenschneider, Johannes; Sgobba, Elvira; Veldmann, Kareen H

    2016-09-20

    Most biotechnological processes are based on glucose that is either present in molasses or generated from starch by enzymatic hydrolysis. At the very high, million-ton scale production volumes, for instance for fermentative production of the biofuel ethanol or of commodity chemicals such as organic acids and amino acids, competing uses of carbon sources e.g. in human and animal nutrition have to be taken into account. Thus, the biotechnological production hosts E. coli, C. glutamicum, pseudomonads, bacilli and Baker's yeast used in these large scale processes have been engineered for efficient utilization of alternative carbon sources. This flexible feedstock concept is central to the use of non-glucose second and third generation feedstocks in the emerging bioeconomy. The metabolic engineering efforts to broaden the substrate scope of E. coli, C. glutamicum, pseudomonads, B. subtilis and yeasts to include non-native carbon sources will be reviewed. Strategies to enable simultaneous consumption of mixtures of native and non-native carbon sources present in biomass hydrolysates will be summarized and a perspective on how to further increase feedstock flexibility for the realization of biorefinery processes will be given. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Development of Biotin-Prototrophic and -Hyperauxotrophic Corynebacterium glutamicum Strains

    Science.gov (United States)

    Miyamoto, Aya; Mutoh, Sumire; Kitano, Yuko; Tajima, Mei; Shirakura, Daisuke; Takasaki, Manami; Mitsuhashi, Satoshi; Takeno, Seiki

    2013-01-01

    To develop the infrastructure for biotin production through naturally biotin-auxotrophic Corynebacterium glutamicum, we attempted to engineer the organism into a biotin prototroph and a biotin hyperauxotroph. To confer biotin prototrophy on the organism, the cotranscribed bioBF genes of Escherichia coli were introduced into the C. glutamicum genome, which originally lacked the bioF gene. The resulting strain still required biotin for growth, but it could be replaced by exogenous pimelic acid, a source of the biotin precursor pimelate thioester linked to either coenzyme A (CoA) or acyl carrier protein (ACP). To bridge the gap between the pimelate thioester and its dedicated precursor acyl-CoA (or -ACP), the bioI gene of Bacillus subtilis, which encoded a P450 protein that cleaves a carbon-carbon bond of an acyl-ACP to generate pimeloyl-ACP, was further expressed in the engineered strain by using a plasmid system. This resulted in a biotin prototroph that is capable of the de novo synthesis of biotin. On the other hand, the bioY gene responsible for biotin uptake was disrupted in wild-type C. glutamicum. Whereas the wild-type strain required approximately 1 μg of biotin per liter for normal growth, the bioY disruptant (ΔbioY) required approximately 1 mg of biotin per liter, almost 3 orders of magnitude higher than the wild-type level. The ΔbioY strain showed a similar high requirement for the precursor dethiobiotin, a substrate for bioB-encoded biotin synthase. To eliminate the dependency on dethiobiotin, the bioB gene was further disrupted in both the wild-type strain and the ΔbioY strain. By selectively using the resulting two strains (ΔbioB and ΔbioBY) as indicator strains, we developed a practical biotin bioassay system that can quantify biotin in the seven-digit range, from approximately 0.1 μg to 1 g per liter. This bioassay proved that the engineered biotin prototroph of C. glutamicum produced biotin directly from glucose, albeit at a marginally

  20. Development of biotin-prototrophic and -hyperauxotrophic Corynebacterium glutamicum strains.

    Science.gov (United States)

    Ikeda, Masato; Miyamoto, Aya; Mutoh, Sumire; Kitano, Yuko; Tajima, Mei; Shirakura, Daisuke; Takasaki, Manami; Mitsuhashi, Satoshi; Takeno, Seiki

    2013-08-01

    To develop the infrastructure for biotin production through naturally biotin-auxotrophic Corynebacterium glutamicum, we attempted to engineer the organism into a biotin prototroph and a biotin hyperauxotroph. To confer biotin prototrophy on the organism, the cotranscribed bioBF genes of Escherichia coli were introduced into the C. glutamicum genome, which originally lacked the bioF gene. The resulting strain still required biotin for growth, but it could be replaced by exogenous pimelic acid, a source of the biotin precursor pimelate thioester linked to either coenzyme A (CoA) or acyl carrier protein (ACP). To bridge the gap between the pimelate thioester and its dedicated precursor acyl-CoA (or -ACP), the bioI gene of Bacillus subtilis, which encoded a P450 protein that cleaves a carbon-carbon bond of an acyl-ACP to generate pimeloyl-ACP, was further expressed in the engineered strain by using a plasmid system. This resulted in a biotin prototroph that is capable of the de novo synthesis of biotin. On the other hand, the bioY gene responsible for biotin uptake was disrupted in wild-type C. glutamicum. Whereas the wild-type strain required approximately 1 μg of biotin per liter for normal growth, the bioY disruptant (ΔbioY) required approximately 1 mg of biotin per liter, almost 3 orders of magnitude higher than the wild-type level. The ΔbioY strain showed a similar high requirement for the precursor dethiobiotin, a substrate for bioB-encoded biotin synthase. To eliminate the dependency on dethiobiotin, the bioB gene was further disrupted in both the wild-type strain and the ΔbioY strain. By selectively using the resulting two strains (ΔbioB and ΔbioBY) as indicator strains, we developed a practical biotin bioassay system that can quantify biotin in the seven-digit range, from approximately 0.1 μg to 1 g per liter. This bioassay proved that the engineered biotin prototroph of C. glutamicum produced biotin directly from glucose, albeit at a marginally

  1. Promoter library-based module combination (PLMC) technology for optimization of threonine biosynthesis in Corynebacterium glutamicum.

    Science.gov (United States)

    Wei, Liang; Xu, Ning; Wang, Yiran; Zhou, Wei; Han, Guoqiang; Ma, Yanhe; Liu, Jun

    2018-05-01

    Due to the lack of efficient control elements and tools, the fine-tuning of gene expression in the multi-gene metabolic pathways is still a great challenge for engineering microbial cell factories, especially for the important industrial microorganism Corynebacterium glutamicum. In this study, the promoter library-based module combination (PLMC) technology was developed to efficiently optimize the expression of genes in C. glutamicum. A random promoter library was designed to contain the putative - 10 (NNTANANT) and - 35 (NNGNCN) consensus motifs, and refined through a three-step screening procedure to achieve numerous genetic control elements with different strength levels, including fluorescence-activated cell sorting (FACS) screening, agar plate screening, and 96-well plate screening. Multiple conventional strategies were employed for further precise characterizations of the promoter library, such as real-time quantitative PCR, sodium dodecyl sulfate polyacrylamide gel electrophoresis, FACS analysis, and the lacZ reporter system. These results suggested that the established promoter elements effectively regulated gene expression and showed varying strengths over a wide range. Subsequently, a multi-module combination technology was created based on the efficient promoter elements for combination and optimization of modules in the multi-gene pathways. Using this technology, the threonine biosynthesis pathway was reconstructed and optimized by predictable tuning expression of five modules in C. glutamicum. The threonine titer of the optimized strain was significantly improved to 12.8 g/L, an approximate 6.1-fold higher than that of the control strain. Overall, the PLMC technology presented in this study provides a rapid and effective method for combination and optimization of multi-gene pathways in C. glutamicum.

  2. A RecET-assisted CRISPR-Cas9 genome editing in Corynebacterium glutamicum.

    Science.gov (United States)

    Wang, Bo; Hu, Qitiao; Zhang, Yu; Shi, Ruilin; Chai, Xin; Liu, Zhe; Shang, Xiuling; Zhang, Yun; Wen, Tingyi

    2018-04-23

    Extensive modification of genome is an efficient manner to regulate the metabolic network for producing target metabolites or non-native products using Corynebacterium glutamicum as a cell factory. Genome editing approaches by means of homologous recombination and counter-selection markers are laborious and time consuming due to multiple round manipulations and low editing efficiencies. The current two-plasmid-based CRISPR-Cas9 editing methods generate false positives due to the potential instability of Cas9 on the plasmid, and require a high transformation efficiency for co-occurrence of two plasmids transformation. Here, we developed a RecET-assisted CRISPR-Cas9 genome editing method using a chromosome-borne Cas9-RecET and a single plasmid harboring sgRNA and repair templates. The inducible expression of chromosomal RecET promoted the frequencies of homologous recombination, and increased the efficiency for gene deletion. Due to the high transformation efficiency of a single plasmid, this method enabled 10- and 20-kb region deletion, 2.5-, 5.7- and 7.5-kb expression cassette insertion and precise site-specific mutation, suggesting a versatility of this method. Deletion of argR and farR regulators as well as site-directed mutation of argB and pgi genes generated the mutant capable of accumulating L-arginine, indicating the stability of chromosome-borne Cas9 for iterative genome editing. Using this method, the model-predicted target genes were modified to redirect metabolic flux towards 1,2-propanediol biosynthetic pathway. The final engineered strain produced 6.75 ± 0.46 g/L of 1,2-propanediol that is the highest titer reported in C. glutamicum. Furthermore, this method is available for Corynebacterium pekinense 1.563, suggesting its universal applicability in other Corynebacterium species. The RecET-assisted CRISPR-Cas9 genome editing method will facilitate engineering of metabolic networks for the synthesis of interested bio-based products from renewable

  3. BIOCHEMICAL AND PHYLOGENETIC STUDIES OF CreD OF Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Muhammad Tausif Chaudhry

    2015-06-01

    Full Text Available CreD characterized as Mg2+-dependent phosphohydrolase with conserved HD domain was involved in 4-cresol metabolism in Corynebacterium glutamicum. Native molecular mass of 54 kDa suggested that the biological unit is a dimer. No deoxynucleotide triphosphate triphosphohydrolase (dNTPase activity was detected for CreD. The apparent Km and Vmax values for 4-nitrophenyl phosphate were 0.35 mM and 16.23 M min-1 mg-1, respectively, while calculated values for kcat and kcat/Km were 0.4 s-1 and 1.14103 M-1 s-1, respectively. Among thiol group inhibitors, iodoacetic acid significantly inhibited phosphohydrolase activity. Sequence identity and phylogenetic analysis suggested universal existence of CreD homologues. Involvement of HD-domain hydrolase in aromatic degradation has not been reported before.

  4. Heterologous expression of the Halothiobacillus neapolitanus carboxysomal gene cluster in Corynebacterium glutamicum.

    Science.gov (United States)

    Baumgart, Meike; Huber, Isabel; Abdollahzadeh, Iman; Gensch, Thomas; Frunzke, Julia

    2017-09-20

    Compartmentalization represents a ubiquitous principle used by living organisms to optimize metabolic flux and to avoid detrimental interactions within the cytoplasm. Proteinaceous bacterial microcompartments (BMCs) have therefore created strong interest for the encapsulation of heterologous pathways in microbial model organisms. However, attempts were so far mostly restricted to Escherichia coli. Here, we introduced the carboxysomal gene cluster of Halothiobacillus neapolitanus into the biotechnological platform species Corynebacterium gluta-micum. Transmission electron microscopy, fluorescence microscopy and single molecule localization microscopy suggested the formation of BMC-like structures in cells expressing the complete carboxysome operon or only the shell proteins. Purified carboxysomes consisted of the expected protein components as verified by mass spectrometry. Enzymatic assays revealed the functional production of RuBisCO in C. glutamicum both in the presence and absence of carboxysomal shell proteins. Furthermore, we could show that eYFP is targeted to the carboxysomes by fusion to the large RuBisCO subunit. Overall, this study represents the first transfer of an α-carboxysomal gene cluster into a Gram-positive model species supporting the modularity and orthogonality of these microcompartments, but also identified important challenges which need to be addressed on the way towards biotechnological application. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Isoprenoid Pyrophosphate-Dependent Transcriptional Regulation of Carotenogenesis in Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Petra Peters-Wendisch

    2017-04-01

    Full Text Available Corynebacterium glutamicum is a natural producer of the C50 carotenoid decaprenoxanthin. The crtEcg0722crtBIYEb operon comprises most of its genes for terpenoid biosynthesis. The MarR-type regulator encoded upstream and in divergent orientation of the carotenoid biosynthesis operon has not yet been characterized. This regulator, named CrtR in this study, is encoded in many actinobacterial genomes co-occurring with terpenoid biosynthesis genes. CrtR was shown to repress the crt operon of C. glutamicum since DNA microarray experiments revealed that transcript levels of crt operon genes were increased 10 to 70-fold in its absence. Transcriptional fusions of a promoter-less gfp gene with the crt operon and crtR promoters confirmed that CrtR represses its own gene and the crt operon. Gel mobility shift assays with purified His-tagged CrtR showed that CrtR binds to a region overlapping with the −10 and −35 promoter sequences of the crt operon. Isoprenoid pyrophosphates interfered with binding of CrtR to its target DNA, a so far unknown mechanism for regulation of carotenogenesis. The molecular details of protein-ligand interactions remain to be studied. Decaprenoxanthin synthesis by C. glutamicum wild type was enhanced 10 to 30-fold upon deletion of crtR and was decreased 5 to 6-fold as result of crtR overexpression. Moreover, deletion of crtR was shown as metabolic engineering strategy to improve production of native and non-native carotenoids including lycopene, β-carotene, C.p. 450 and sarcinaxanthin.

  6. Function of Corynebacterium glutamicum promoters in Eschrichia coli, Streptomyces lividans, and Baccillus subtilis

    Czech Academy of Sciences Publication Activity Database

    Pátek, Miroslav; Muth, G.; Wohlleben, W.

    2003-01-01

    Roč. 104, - (2003), s. 325-334 ISSN 0168-1656 R&D Projects: GA AV ČR IPP1050128; GA ČR GA525/01/0916 Institutional research plan: CEZ:AV0Z5020903 Keywords : corynebacterium glutamicum * escherichia coli * promoters Subject RIV: EE - Microbiology, Virology Impact factor: 2.543, year: 2003

  7. Physiological roles of sigma factor SigD in Corynebacterium glutamicum

    Czech Academy of Sciences Publication Activity Database

    Taniguchi, H.; Busche, T.; Patschkowski, T.; Niehaus, K.; Pátek, Miroslav; Kalinowski, J.; Wendisch, V.F.

    2017-01-01

    Roč. 17, č. 158 (2017), s. 158 ISSN 1471-2180 R&D Projects: GA ČR(CZ) GA17-06991S Institutional support: RVO:61388971 Keywords : Corynebacterium glutamicum * Sigma factor * SigD Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.644, year: 2016

  8. Assignment of sigma factors of RNA polymerase to promoters in Corynebacterium glutamicum

    Czech Academy of Sciences Publication Activity Database

    Dostálová, Hana; Holátko, Jiří; Busche, T.; Rucká, Lenka; Rapoport, Andrey; Halada, Petr; Nešvera, Jan; Kalinowski, J.; Pátek, Miroslav

    2017-01-01

    Roč. 7, JUN 23 (2017), s. 1-13, č. článku 133. ISSN 2191-0855 R&D Projects: GA ČR(CZ) GA17-06991S Institutional support: RVO:61388971 Keywords : Corynebacterium glutamicum * Promoter * Sigma factor Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.825, year: 2016

  9. Formation of xylitol and xylitol-5-phosphate and its impact on growth of d-xylose-utilizing Corynebacterium glutamicum strains.

    Science.gov (United States)

    Radek, Andreas; Müller, Moritz-Fabian; Gätgens, Jochem; Eggeling, Lothar; Krumbach, Karin; Marienhagen, Jan; Noack, Stephan

    2016-08-10

    Wild-type Corynebacterium glutamicum has no endogenous metabolic activity for utilizing the lignocellulosic pentose d-xylose for cell growth. Therefore, two different engineering approaches have been pursued resulting in platform strains harbouring a functional version of either the Isomerase (ISO) or the Weimberg (WMB) pathway for d-xylose assimilation. In a previous study we found for C. glutamicum WMB by-product formation of xylitol during growth on d-xylose and speculated that the observed lower growth rates are due to the growth inhibiting effect of this compound. Based on a detailed phenotyping of the ISO, WMB and the wild-type strain of C. glutamicum, we here show that this organism has a natural capability to synthesize xylitol from d-xylose under aerobic cultivation conditions. We furthermore observed the intracellular accumulation of xylitol-5-phosphate as a result of the intracellular phosphorylation of xylitol, which was particularly pronounced in the C. glutamicum ISO strain. Interestingly, low amounts of supplemented xylitol strongly inhibit growth of this strain on d-xylose, d-glucose and d-arabitol. These findings demonstrate that xylitol is a suitable substrate of the endogenous xylulokinase (XK, encoded by xylB) and its overexpression in the ISO strain leads to a significant phosphorylation of xylitol in C. glutamicum. Therefore, in order to circumvent cytotoxicity by xylitol-5-phosphate, the WMB pathway represents an interesting alternative route for engineering C. glutamicum towards efficient d-xylose utilization. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Molecular cloning and expression of Corynebacterium glutamicum genes for amino acid synthesis in Escherichia coli cells

    International Nuclear Information System (INIS)

    Beskrovnaya, O.Yu.; Fonshtein, M.Yu.; Kolibaba, L.G.; Yankovskii, N.K.; Debabov, V.G.

    1989-01-01

    Molecular cloning of Corynebacterium glutamicum genes for threonine and lysine synthesis has been done in Escherichia coli cells. The clonal library of EcoRI fragments of chromosomal DNA of C. glutamicum was constructed on the plasmid vector λpSL5. The genes for threonine and lysine synthesis were identified by complementation of E. coli mutations in thrB and lysA genes, respectively. Recombinant plasmids, isolated from independent ThrB + clone have a common 4.1-kb long EcoRI DNA fragment. Hybrid plasmids isolated from LysA + transductants of E. coli have common 2.2 and 3.3 kb long EcoRI fragments of C. glutamicum DNA. The hybrid plasmids consistently transduced the markers thrB + and lysA + . The Southern hybridization analysis showed that the cloned DNA fragments hybridized with the fragments of identical length in C. glutamicum chromosomes

  11. Improvement of succinate production by release of end-product inhibition in Corynebacterium glutamicum.

    Science.gov (United States)

    Chung, Soon-Chun; Park, Joon-Song; Yun, Jiae; Park, Jin Hwan

    2017-03-01

    Succinate is a renewable-based platform chemical that may be used to produce a wide range of chemicals including 1,4-butanediol, tetrahydrofurane, and γ-butyrolactone. However, industrial fermentation of organic acids is often subject to end-product inhibition, which significantly retards cell growth and limits metabolic activities and final productivity. In this study, we report the development of metabolically engineered Corynebacterium glutamicum for high production of succinate by release of end-product inhibition coupled with an increase of key metabolic flux. It was found that the rates of glucose consumption and succinate production were significantly reduced by extracellular succinate in an engineered strain, S003. To understand the mechanism underlying the inhibition by succinate, comparative transcriptome analysis was performed. Among the downregulated genes, overexpression of the NCgl0275 gene was found to suppress the inhibition of glucose consumption and succinate production, resulting in a 37.7% increase in succinate production up to 55.4g/L in fed-batch fermentation. Further improvement was achieved by increasing the metabolic flux from PEP to OAA. The final engineered strain was able to produce 152.2g/L succinate, the highest production reported to date, with a yield of 1.1g/g glucose under anaerobic condition. These results suggest that the release of end-product inhibition coupled with an increase in key metabolic flux is a promising strategy for enhancing production of succinate. Copyright © 2017. Published by Elsevier Inc.

  12. Development of a CRISPR/Cas9 genome editing toolbox for Corynebacterium glutamicum.

    Science.gov (United States)

    Liu, Jiao; Wang, Yu; Lu, Yujiao; Zheng, Ping; Sun, Jibin; Ma, Yanhe

    2017-11-16

    Corynebacterium glutamicum is an important industrial workhorse and advanced genetic engineering tools are urgently demanded. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) have revolutionized the field of genome engineering. The CRISPR/Cas9 system that utilizes NGG as protospacer adjacent motif (PAM) and has good targeting specificity can be developed into a powerful tool for efficient and precise genome editing of C. glutamicum. Herein, we developed a versatile CRISPR/Cas9 genome editing toolbox for C. glutamicum. Cas9 and gRNA expression cassettes were reconstituted to combat Cas9 toxicity and facilitate effective termination of gRNA transcription. Co-transformation of Cas9 and gRNA expression plasmids was exploited to overcome high-frequency mutation of cas9, allowing not only highly efficient gene deletion and insertion with plasmid-borne editing templates (efficiencies up to 60.0 and 62.5%, respectively) but also simple and time-saving operation. Furthermore, CRISPR/Cas9-mediated ssDNA recombineering was developed to precisely introduce small modifications and single-nucleotide changes into the genome of C. glutamicum with efficiencies over 80.0%. Notably, double-locus editing was also achieved in C. glutamicum. This toolbox works well in several C. glutamicum strains including the widely-used strains ATCC 13032 and ATCC 13869. In this study, we developed a CRISPR/Cas9 toolbox that could facilitate markerless gene deletion, gene insertion, precise base editing, and double-locus editing in C. glutamicum. The CRISPR/Cas9 toolbox holds promise for accelerating the engineering of C. glutamicum and advancing its application in the production of biochemicals and biofuels.

  13. Effects of phosphoenolpyruvate carboxylase desensitization on glutamic acid production in Corynebacterium glutamicum ATCC 13032.

    Science.gov (United States)

    Wada, Masaru; Sawada, Kazunori; Ogura, Kotaro; Shimono, Yuta; Hagiwara, Takuya; Sugimoto, Masakazu; Onuki, Akiko; Yokota, Atsushi

    2016-02-01

    Phosphoenolpyruvate carboxylase (PEPC) in Corynebacterium glutamicum ATCC13032, a glutamic-acid producing actinobacterium, is subject to feedback inhibition by metabolic intermediates such as aspartic acid and 2-oxoglutaric acid, which implies the importance of PEPC in replenishing oxaloacetic acid into the TCA cycle. Here, we investigated the effects of feedback-insensitive PEPC on glutamic acid production. A single amino-acid substitution in PEPC, D299N, was found to relieve the feedback control by aspartic acid, but not by 2-oxoglutaric acid. A simple mutant, strain R1, having the D299N substitution in PEPC was constructed from ATCC 13032 using the double-crossover chromosome replacement technique. Strain R1 produced glutamic acid at a concentration of 31.0 g/L from 100 g/L glucose in a jar fermentor culture under biotin-limited conditions, which was significantly higher than that of the parent, 26.0 g/L (1.19-fold), indicative of the positive effect of desensitized PEPC on glutamic acid production. Another mutant, strain DR1, having both desensitized PEPC and PYK-gene deleted mutations, was constructed in a similar manner using strain D1 with a PYK-gene deleted mutation as the parent. This mutation had been shown to enhance glutamic acid production in our previous study. Although marginal, strain D1 produced higher glutamic acid, 28.8 g/L, than ATCC13032 (1.11-fold). In contrast, glutamic acid production by strain DR-1 was elevated up to 36.9 g/L, which was 1.42-fold higher than ATCC13032 and significantly higher than the other three strains. The results showed a synergistic effect of these two mutations on glutamic acid production in C. glutamicum. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum.

    Science.gov (United States)

    Sato, Hiroki; Orishimo, Keita; Shirai, Tomokazu; Hirasawa, Takashi; Nagahisa, Keisuke; Shimizu, Hiroshi; Wachi, Masaaki

    2008-07-01

    Corynebacterium glutamicum is a biotin auxotrophic bacterium in which glutamate production is induced under biotin-limited conditions. During glutamate production, anaplerotic reactions catalyzed by phosphoenolpyruvate carboxylase (PEPC) and a biotin-containing enzyme pyruvate carboxylase (PC) are believed to play an important role in supplying oxaloacetate in the tricarboxylic acid cycle. To understand the distinct roles of PEPC and PC on glutamate production by C. glutamicum, we observed glutamate production induced under biotin-limited conditions in the disruptants of the genes encoding PEPC (ppc) and PC (pyc), respectively. The pyc disruptant retained the ability to produce high amounts of glutamate, and lactate was simultaneously produced probably due to the increased intracellular pyruvate levels. On the other hand, the ppc knockout mutant could not produce glutamate. Additionally, glutamate production in the pyc disruptant was enhanced by overexpression of ppc rather than disruption of the lactate dehydrogenase gene (ldh), which is involved in lactate production. Metabolic flux analysis based on the 13C-labeling experiment and measurement of 13C-enrichment in glutamate using nuclear magnetic resonance spectroscopy revealed that the flux for anaplerotic reactions in the pyc disruptant was lower than that in the wild type, concomitantly increasing the flux for lactate formation. Moreover, overexpression of ppc increased this flux in both the pyc disruptant and the wild type. Our results suggest that the PEPC-catalyzed anaplerotic reaction is necessary for glutamate production induced under biotin-limited conditions, because PC is not active during glutamate production, and overexpression of ppc effectively enhances glutamate production under biotin-limited conditions.

  15. Integrated Analysis of the Transcriptome and Metabolome of Corynebacterium glutamicum during Penicillin-Induced Glutamic Acid Production.

    Science.gov (United States)

    Hirasawa, Takashi; Saito, Masaki; Yoshikawa, Katsunori; Furusawa, Chikara; Shmizu, Hiroshi

    2018-05-01

    Corynebacterium glutamicum is known for its ability to produce glutamic acid and has been utilized for the fermentative production of various amino acids. Glutamic acid production in C. glutamicum is induced by penicillin. In this study, the transcriptome and metabolome of C. glutamicum is analyzed to understand the mechanism of penicillin-induced glutamic acid production. Transcriptomic analysis with DNA microarray revealed that expression of some glycolysis- and TCA cycle-related genes, which include those encoding the enzymes involved in conversion of glucose to 2-oxoglutaric acid, is upregulated after penicillin addition. Meanwhile, expression of some TCA cycle-related genes, encoding the enzymes for conversion of 2-oxoglutaric acid to oxaloacetic acid, and the anaplerotic reactions decreased. In addition, expression of NCgl1221 and odhI, encoding proteins involved in glutamic acid excretion and inhibition of the 2-oxoglutarate dehydrogenase, respectively, is upregulated. Functional category enrichment analysis of genes upregulated and downregulated after penicillin addition revealed that genes for signal transduction systems are enriched among upregulated genes, whereas those for energy production and carbohydrate and amino acid metabolisms are enriched among the downregulated genes. As for the metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry, the intracellular content of most metabolites of the glycolysis and the TCA cycle decreased dramatically after penicillin addition. Overall, these results indicate that the cellular metabolism and glutamic acid excretion are mainly optimized at the transcription level during penicillin-induced glutamic acid production by C. glutamicum. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Enhanced production of recombinant proteins with Corynebacterium glutamicum by deletion of insertion sequences (IS elements).

    Science.gov (United States)

    Choi, Jae Woong; Yim, Sung Sun; Kim, Min Jeong; Jeong, Ki Jun

    2015-12-29

    In most bacteria, various jumping genetic elements including insertion sequences elements (IS elements) cause a variety of genetic rearrangements resulting in harmful effects such as genome and recombinant plasmid instability. The genetic stability of a plasmid in a host is critical for high-level production of recombinant proteins, and in this regard, the development of an IS element-free strain could be a useful strategy for the enhanced production of recombinant proteins. Corynebacterium glutamicum, which is a workhorse in the industrial-scale production of various biomolecules including recombinant proteins, also has several IS elements, and it is necessary to identify the critical IS elements and to develop IS element deleted strain. From the cultivation of C. glutamicum harboring a plasmid for green fluorescent protein (GFP) gene expression, non-fluorescent clones were isolated by FACS (fluorescent activated cell sorting). All the isolated clones had insertions of IS elements in the GFP coding region, and two major IS elements (ISCg1 and ISCg2 families) were identified. By co-cultivating cells harboring either the isolated IS element-inserted plasmid or intact plasmid, it was clearly confirmed that cells harboring the IS element-inserted plasmids became dominant during the cultivation due to their growth advantage over cells containing intact plasmids, which can cause a significant reduction in recombinant protein production during cultivation. To minimize the harmful effects of IS elements on the expression of heterologous genes in C. glutamicum, two IS element free C. glutamicum strains were developed in which each major IS element was deleted, and enhanced productivity in the engineered C. glutamicum strain was successfully demonstrated with three models: GFP, poly(3-hydroxybutyrate) [P(3HB)] and γ-aminobutyrate (GABA). Our findings clearly indicate that the hopping of IS elements could be detrimental to the production of recombinant proteins in C

  17. L-Serine overproduction with minimization of by-product synthesis by engineered Corynebacterium glutamicum.

    Science.gov (United States)

    Zhu, Qinjian; Zhang, Xiaomei; Luo, Yuchang; Guo, Wen; Xu, Guoqiang; Shi, Jinsong; Xu, Zhenghong

    2015-02-01

    The direct fermentative production of L-serine by Corynebacterium glutamicum from sugars is attractive. However, superfluous by-product accumulation and low L-serine productivity limit its industrial production on large scale. This study aimed to investigate metabolic and bioprocess engineering strategies towards eliminating by-products as well as increasing L-serine productivity. Deletion of alaT and avtA encoding the transaminases and introduction of an attenuated mutant of acetohydroxyacid synthase (AHAS) increased both L-serine production level (26.23 g/L) and its productivity (0.27 g/L/h). Compared to the parent strain, the by-products L-alanine and L-valine accumulation in the resulting strain were reduced by 87 % (from 9.80 to 1.23 g/L) and 60 % (from 6.54 to 2.63 g/L), respectively. The modification decreased the metabolic flow towards the branched-chain amino acids (BCAAs) and induced to shift it towards L-serine production. Meanwhile, it was found that corn steep liquor (CSL) could stimulate cell growth and increase sucrose consumption rate as well as L-serine productivity. With addition of 2 g/L CSL, the resulting strain showed a significant improvement in the sucrose consumption rate (72 %) and the L-serine productivity (67 %). In fed-batch fermentation, 42.62 g/L of L-serine accumulation was achieved with a productivity of 0.44 g/L/h and yield of 0.21 g/g sucrose, which was the highest production of L-serine from sugars to date. The results demonstrated that combined metabolic and bioprocess engineering strategies could minimize by-product accumulation and improve L-serine productivity.

  18. Engineering biotin prototrophic Corynebacterium glutamicum strains for amino acid, diamine and carotenoid production.

    Science.gov (United States)

    Peters-Wendisch, P; Götker, S; Heider, S A E; Komati Reddy, G; Nguyen, A Q; Stansen, K C; Wendisch, V F

    2014-12-20

    The Gram-positive Corynebacterium glutamicum is auxotrophic for biotin. Besides the biotin uptake system BioYMN and the transcriptional regulator BioQ, this bacterium possesses functional enzymes for the last three reactions of biotin synthesis starting from pimeloyl-CoA. Heterologous expression of bioF from the Gram-negative Escherichia coli enabled biotin synthesis from pimelic acid added to the medium, but expression of bioF together with bioC and bioH from E. coli did not entail biotin prototrophy. Heterologous expression of bioWAFDBI from Bacillus subtilis encoding another biotin synthesis pathway in C. glutamicum allowed for growth in biotin-depleted media. Stable growth of the recombinant was observed without biotin addition for eight transfers to biotin-depleted medium while the empty vector control stopped growth after the first transfer. Expression of bioWAFDBI from B. subtilis in C. glutamicum strains overproducing the amino acids l-lysine and l-arginine, the diamine putrescine, and the carotenoid lycopene, respectively, enabled formation of these products under biotin-depleted conditions. Thus, biotin-prototrophic growth and production by recombinant C. glutamicum were achieved. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin.

    Directory of Open Access Journals (Sweden)

    Can Chen

    Full Text Available Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

  20. Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin.

    Science.gov (United States)

    Chen, Can; Pan, Junfeng; Yang, Xiaobing; Guo, Chenghao; Ding, Wei; Si, Meiru; Zhang, Yi; Shen, Xihui; Wang, Yao

    2016-01-01

    Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

  1. Integration of ARTP mutagenesis with biosensor-mediated high-throughput screening to improve L-serine yield in Corynebacterium glutamicum.

    Science.gov (United States)

    Zhang, Xin; Zhang, Xiaomei; Xu, Guoqiang; Zhang, Xiaojuan; Shi, Jinsong; Xu, Zhenghong

    2018-05-03

    L-Serine is widely used in the pharmaceutical, food, and cosmetics industries. Although direct fermentative production of L-serine from sugar in Corynebacterium glutamicum has been achieved, the L-serine yield remains relatively low. In this study, atmospheric and room temperature plasma (ARTP) mutagenesis was used to improve the L-serine yield based on engineered C. glutamicum ΔSSAAI strain. Subsequently, we developed a novel high-throughput screening method using a biosensor constructed based on NCgl0581, a transcriptional factor specifically responsive to L-serine, so that L-serine concentration within single cell of C. glutamicum can be monitored via fluorescence-activated cell sorting (FACS). Novel L-serine-producing mutants were isolated from a large library of mutagenized cells. The mutant strain A36-pDser was screened from 1.2 × 10 5 cells, and the magnesium ion concentration in the medium was optimized specifically for this mutant. C. glutamicum A36-pDser accumulated 34.78 g/L L-serine with a yield of 0.35 g/g sucrose, which were 35.9 and 66.7% higher than those of the parent C. glutamicum ΔSSAAI-pDser strain, respectively. The L-serine yield achieved in this mutant was the highest of all reported L-serine-producing strains of C. glutamicum. Moreover, the whole-genome sequencing identified 11 non-synonymous mutations of genes associated with metabolic and transport pathways, which might be responsible for the higher L-serine production and better cell growth in C. glutamicum A36-pDser. This study explored an effective mutagenesis strategy and reported a novel high-throughput screening method for the development of L-serine-producing strains.

  2. APLICACION DE TECNICAS DE INGENIERIA METABOLICA AL MEJORAMIENTO DE LA PRODUCCION DE TREHALOSA POR CORYNEBACTERIUM GLUTAMICUM.

    OpenAIRE

    PADILLA IGLESIAS, LEANDRO MAURICIO

    2004-01-01

    La Trehalosa es un disacárido con tremendas aplicaciones en la industria biotecnológica y alimenticia. Este compuesto se encuentra en muchos organismos, a causa de su capacidad de proteger las células contra el calor y la deshidratación. Un ejemplo, es la bacteria Gram-positiva Corynebacterium glutamicum, la cual sintetiza trehalosa a través de dos rutas principales, TreYZ y OtsBA, usando ADP-glucosa (especulativamente) y UDP-glucosa, respectivamente, como dadores de unidades de ...

  3. Dual production of poly(3-hydroxybutyrate) and glutamate using variable biotin concentrations in Corynebacterium glutamicum.

    Science.gov (United States)

    Jo, Sung-Jin; Leong, Chean Ring; Matsumoto, Ken'ichiro; Taguchi, Seiichi

    2009-04-01

    We previously synthesized poly(3-hydroxybutyrate) [P(3HB)] in recombinant Corynebacterium glutamicum, a prominent producer of amino acids. In this study, a two-step cultivation was established for the dual production of glutamate and P(3HB) due to the differences in the optimal concentration of biotin. Glutamate was extracellularly produced first under the biotin-limited condition of 0.3 microg/L. Production was then shifted to P(3HB) by addition of biotin to a total concentration of 9 microg/L. The final products obtained were 18 g/L glutamate and 36 wt% of P(3HB).

  4. Biotin protein ligase from Corynebacterium glutamicum: role for growth and L: -lysine production.

    Science.gov (United States)

    Peters-Wendisch, P; Stansen, K C; Götker, S; Wendisch, V F

    2012-03-01

    Corynebacterium glutamicum is a biotin auxotrophic Gram-positive bacterium that is used for large-scale production of amino acids, especially of L-glutamate and L-lysine. It is known that biotin limitation triggers L-glutamate production and that L-lysine production can be increased by enhancing the activity of pyruvate carboxylase, one of two biotin-dependent proteins of C. glutamicum. The gene cg0814 (accession number YP_225000) has been annotated to code for putative biotin protein ligase BirA, but the protein has not yet been characterized. A discontinuous enzyme assay of biotin protein ligase activity was established using a 105aa peptide corresponding to the carboxyterminus of the biotin carboxylase/biotin carboxyl carrier protein subunit AccBC of the acetyl CoA carboxylase from C. glutamicum as acceptor substrate. Biotinylation of this biotin acceptor peptide was revealed with crude extracts of a strain overexpressing the birA gene and was shown to be ATP dependent. Thus, birA from C. glutamicum codes for a functional biotin protein ligase (EC 6.3.4.15). The gene birA from C. glutamicum was overexpressed and the transcriptome was compared with the control strain revealing no significant gene expression changes of the bio-genes. However, biotin protein ligase overproduction increased the level of the biotin-containing protein pyruvate carboxylase and entailed a significant growth advantage in glucose minimal medium. Moreover, birA overexpression resulted in a twofold higher L-lysine yield on glucose as compared with the control strain.

  5. Immobilazation of aerobic microorganisms on glassy sintered material, illustrated by the example of the production of L leucine using Corynebacterium glutamicum. Immobilisierung von aeroben Mikroorganismen an Glassintermaterial am Beispiel der L-Leucin-Produktion mit Corynebacterium glutamicum

    Energy Technology Data Exchange (ETDEWEB)

    Buechs, J.

    1988-12-01

    The aim of this study was to develop the carrier fixation of aerobic microorganisms on open-pore sintered glass material. The fermentative production of L-leucine from {alpha} cetonic isocaproic acid with Corynebacterium glutamicum was chosen as an example of a microbial process with a high demand of oxygen. (orig.).

  6. Pyruvate:Quinone Oxidoreductase in Corynebacterium glutamicum: Molecular Analysis of the pqo Gene, Significance of the Enzyme, and Phylogenetic Aspects

    Czech Academy of Sciences Publication Activity Database

    Schreiner, M. E.; Riedel, Ch.; Holátko, Jiří; Pátek, Miroslav; Eikmanns, B. J.

    2006-01-01

    Roč. 188, č. 4 (2006), s. 1341-1350 ISSN 0021-9193 R&D Projects: GA ČR GA525/04/0548 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * pqo * molecular analysis Subject RIV: EE - Microbiology, Virology Impact factor: 3.993, year: 2006

  7. FudC, a protein primarily responsible for furfural detoxification in Corynebacterium glutamicum.

    Science.gov (United States)

    Tsuge, Yota; Kudou, Motonori; Kawaguchi, Hideo; Ishii, Jun; Hasunuma, Tomohisa; Kondo, Akihiko

    2016-03-01

    Lignocellulosic hydrolysates contain compounds that inhibit microbial growth and fermentation, thereby decreasing the productivity of biofuel and biochemical production. In particular, the heterocyclic aldehyde furfural is one of the most toxic compounds found in these hydrolysates. We previously demonstrated that Corynebacterium glutamicum converts furfural into the less toxic compounds furfuryl alcohol and 2-furoic acid. To date, however, the genes involved in these oxidation and reduction reactions have not been identified in the C. glutamicum genome. Here, we show that Cgl0331 (designated FudC) is mainly responsible for the reduction of furfural into furfuryl alcohol in C. glutamicum. Deletion of the gene encoding FudC markedly diminished the in vivo reduction of furfural to furfuryl alcohol. Purified His-tagged FudC protein from Escherichia coli was also shown to convert furfural into furfuryl alcohol in an in vitro reaction utilizing NADPH, but not NADH, as a cofactor. Kinetic measurements demonstrated that FudC has a high affinity for furfural but has a narrow substrate range for other aldehydes compared to the protein responsible for furfural reduction in E. coli.

  8. Enhancing poly-γ-glutamic acid production in Bacillus amyloliquefaciens by introducing the glutamate synthesis features from Corynebacterium glutamicum.

    Science.gov (United States)

    Feng, Jun; Quan, Yufen; Gu, Yanyan; Liu, Fenghong; Huang, Xiaozhong; Shen, Haosheng; Dang, Yulei; Cao, Mingfeng; Gao, Weixia; Lu, Xiaoyun; Wang, Yi; Song, Cunjiang; Wang, Shufang

    2017-05-22

    Poly-γ-glutamic acid (γ-PGA) is a valuable polymer with glutamate as its sole precursor. Enhancement of the intracellular glutamate synthesis is a very important strategy for the improvement of γ-PGA production, especially for those glutamate-independent γ-PGA producing strains. Corynebacterium glutamicum has long been used for industrial glutamate production and it exhibits some unique features for glutamate synthesis; therefore introduction of these metabolic characters into the γ-PGA producing strain might lead to increased intracellular glutamate availability, and thus ultimate γ-PGA production. In this study, the unique glutamate synthesis features from C. glutamicum was introduced into the glutamate-independent γ-PGA producing Bacillus amyloliquefaciens NK-1 strain. After introducing the energy-saving NADPH-dependent glutamate dehydrogenase (NADPH-GDH) pathway, the NK-1 (pHT315-gdh) strain showed slightly increase (by 9.1%) in γ-PGA production. Moreover, an optimized metabolic toggle switch for controlling the expression of ɑ-oxoglutarate dehydrogenase complex (ODHC) was introduced into the NK-1 strain, because it was previously shown that the ODHC in C. glutamicum was completely inhibited when glutamate was actively produced. The obtained NK-PO1 (pHT01-xylR) strain showed 66.2% higher γ-PGA production than the NK-1 strain. However, the further combination of these two strategies (introducing both NADPH-GDH pathway and the metabolic toggle switch) did not lead to further increase of γ-PGA production but rather the resultant γ-PGA production was even lower than that in the NK-1 strain. We proposed new metabolic engineering strategies to improve the γ-PGA production in B. amyloliquefaciens. The NK-1 (pHT315-gdh) strain with the introduction of NADPH-GDH pathway showed 9.1% improvement in γ-PGA production. The NK-PO1 (pHT01-xylR) strain with the introduction of a metabolic toggle switch for controlling the expression of ODHC showed 66.2% higher

  9. Bioconversion of sugar cane molasses into glutamic acid by gamma irradiated corynebacterium glutamicum

    International Nuclear Information System (INIS)

    El-Batal, A.I.

    1996-01-01

    Corynebacterium glutamicum (ATCC 13058) was used for glutamic acid production from sugar cane molasses which contain sufficient. The addition of 5 units ml 4 of penicillin G was superior in glutamic acid production (11.5 g L 4 ). Tweens and their saturated fatty acids were effective on the accumulation of glutamic acid in the culture medium and the maximum yield (16.6 g L 4 ) was the addition of 5 mg ml 4 Tween 40. Gamma irradiation prior to Tween-40 treatment of bacterial cells resulted in an obvious increase in glutamic acid production and it was maximum (23.72 g L 4 ) at 0.1 k Gy exposure dose of inocula. 5 tabs

  10. Construction of in vitro transcription system for Corynebacterium glutamicum and its use in the recognition of promoters of different classes.

    Science.gov (United States)

    Holátko, Jiří; Silar, Radoslav; Rabatinová, Alžbeta; Sanderová, Hana; Halada, Petr; Nešvera, Jan; Krásný, Libor; Pátek, Miroslav

    2012-10-01

    To facilitate transcription studies in Corynebacterium glutamicum, we have developed an in vitro transcription system for this bacterium used as an industrial producer of amino acids and a model organism for actinobacteria. This system consists of C. glutamicum RNA polymerase (RNAP) core (α2, β, β'), a sigma factor and a promoter-carrying DNA template, that is specifically recognized by the RNAP holoenzyme formed. The RNAP core was purified from the C. glutamicum strain with the modified rpoC gene, which produced His-tagged β' subunit. The C. glutamicum sigA and sigH genes were cloned and overexpressed using the Escherichia coli plasmid vector, and the sigma subunits σ(A) and σ(H) were purified by affinity chromatography. Using the reconstituted C. glutamicum holo-RNAPs, recognition of the σ(A)- and σ(H)-dependent promoters and synthesis of the specific transcripts was demonstrated. The developed in vitro transcription system is a novel tool that can be used to directly prove the specific recognition of a promoter by the particular σ factor(s) and to analyze transcriptional control by various regulatory proteins in C. glutamicum.

  11. Utilization of fermentation waste (Corynebacterium glutamicum) for biosorption of Reactive Black 5 from aqueous solution

    International Nuclear Information System (INIS)

    Vijayaraghavan, K.; Yun, Yeoung-Sang

    2007-01-01

    A fermentation waste, Corynebacterium glutamicum, was successfully employed as a biosorbent for Reactive Black 5 (RB5) from aqueous solution. This paper initially studied the effect of pretreatment on the biosorption capacity of C. glutamicum toward RB5, using several chemical agents, such as HCl, H 2 SO 4 , HNO 3 , NaOH, Na 2 CO 3 , CaCl 2 and NaCl. Among these reagents, 0.1 M HNO 3 gave the maximum enhancement of the RB5 uptake, exhibiting 195 mg/g at pH 1 with an initial RB5 concentration of 500 mg/l. The solution pH and temperature were found to affect the biosorption capacity, and the biosorption isotherms derived at different pHs and temperatures revealed that a low pH (pH 1) and high temperature (35 deg. C) favored biosorption. The biosorption isotherm was well represented using three-parameter models (Redlich-Peterson and Sips) compared to two-parameter models (Langmuir and Freundlich models). As a result, high correlation coefficients and low average percentage error values were observed for three-parameter models. A maximum RB5 uptake of 419 mg/g was obtained at pH 1 and a temperature of 35 deg. C, according to the Langmuir model. The kinetics of the biosorption process with different initial concentrations (500-2000 mg/l) was also monitored, and the data were analyzed using pseudo-first and pseudo-second order models, with the latter describing the data well. Various thermodynamic parameters, such as ΔG o , ΔH o and ΔS o , were calculated, indicating that the present system was a spontaneous and endothermic process. The use of a 0.1 M NaOH solution successfully desorbed almost all the dye molecules from dye-loaded C. glutamicum biomass at different solid-to-liquid ratios examined

  12. Detoxification of furfural in Corynebacterium glutamicum under aerobic and anaerobic conditions.

    Science.gov (United States)

    Tsuge, Yota; Hori, Yoshimi; Kudou, Motonori; Ishii, Jun; Hasunuma, Tomohisa; Kondo, Akihiko

    2014-10-01

    The toxic fermentation inhibitors in lignocellulosic hydrolysates raise serious problems for the microbial production of fuels and chemicals. Furfural is considered to be one of the most toxic compounds among these inhibitors. Here, we describe the detoxification of furfural in Corynebacterium glutamicum ATCC13032 under both aerobic and anaerobic conditions. Under aerobic culture conditions, furfuryl alcohol and 2-furoic acid were produced as detoxification products of furfural. The ratio of the products varied depending on the initial furfural concentration. Neither furfuryl alcohol nor 2-furoic acid showed any toxic effect on cell growth, and both compounds were determined to be the end products of furfural degradation. Interestingly, unlike under aerobic conditions, most of the furfural was converted to furfuryl alcohol under anaerobic conditions, without affecting the glucose consumption rate. Both the NADH/NAD(+) and NADPH/NADP(+) ratio decreased in the accordance with furfural concentration under both aerobic and anaerobic conditions. These results indicate the presence of a single or multiple endogenous enzymes with broad and high affinity for furfural and co-factors in C. glutamicum ATCC13032.

  13. Analysis of different DNA fragments of Corynebacterium glutamicum complementing dapE of Escherichia coli.

    Science.gov (United States)

    Wehrmann, A; Eggeling, L; Sahm, H

    1994-12-01

    In Corynebacterium glutamicum L-lysine is synthesized simultaneously via the succinylase and dehydrogenase variant of the diaminopimelate pathway. Starting from a strain with a disrupted dehydrogenase gene, three different-sized DNA fragments were isolated which complemented defective Escherichia coli mutants in the succinylase pathway. Enzyme studies revealed that in one case the dehydrogenase gene had apparently been reconstituted in the heterologous host. The two other fragments resulted in desuccinylase activity; one of them additionally in succinylase activity. However, the physical analysis showed that structural changes had taken place in all fragments. Using a probe derived from one of the fragments we isolated a 3.4 kb BamHI DNA fragment without selective pressure (by colony hybridization). This was structurally intact and proved functionally to result in tenfold desuccinylase overexpression. The nucleotide sequence of a 1966 bp fragment revealed the presence of one truncated open reading frame of unknown function and that of dapE encoding N-succinyl diaminopimelate desuccinylase (EC 3.5.1.18). The deduced amino acid sequence of the dapE gene product shares 23% identical residues with that from E. coli. The C. glutamicum gene now available is the first gene from the succinylase branch of lysine synthesis of this biotechnologically important organism.

  14. From zero to hero - production of bio-based nylon from renewable resources using engineered Corynebacterium glutamicum.

    Science.gov (United States)

    Kind, Stefanie; Neubauer, Steffi; Becker, Judith; Yamamoto, Motonori; Völkert, Martin; Abendroth, Gregory von; Zelder, Oskar; Wittmann, Christoph

    2014-09-01

    Polyamides are important industrial polymers. Currently, they are produced exclusively from petrochemical monomers. Herein, we report the production of a novel bio-nylon, PA5.10 through an integration of biological and chemical approaches. First, systems metabolic engineering of Corynebacterium glutamicum was used to create an effective microbial cell factory for the production of diaminopentane as the polymer building block. In this way, a hyper-producer, with a high diaminopentane yield of 41% in shake flask culture, was generated. Subsequent fed-batch production of C. glutamicum DAP-16 allowed a molar yield of 50%, a productivity of 2.2gL(-1)h(-1), and a final titer of 88gL(-1). The streamlined producer accumulated diaminopentane without generating any by-products. Solvent extraction from alkalized broth and two-step distillation provided highly pure diaminopentane (99.8%), which was then directly accessible for poly-condensation. Chemical polymerization with sebacic acid, a ten-carbon dicarboxylic acid derived from castor plant oil, yielded the bio-nylon, PA5.10. In pure form and reinforced with glass fibers, the novel 100% bio-polyamide achieved an excellent melting temperature and the mechanical strength of the well-established petrochemical polymers, PA6 and PA6.6. It even outperformed the oil-based products in terms of having a 6% lower density. It thus holds high promise for applications in energy-friendly transportation. The demonstration of a novel route for generation of bio-based nylon from renewable sources opens the way to production of sustainable bio-polymers with enhanced material properties and represents a milestone in industrial production. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. High-resolution detection of DNA binding sites of the global transcriptional regulator GlxR in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Jungwirth, Britta; Sala, Claudia; Kohl, Thomas A

    2013-01-01

    of the 6C non-coding RNA gene and to non-canonical DNA binding sites within protein-coding regions. The present study underlines the dynamics within the GlxR regulon by identifying in vivo targets during growth on glucose and contributes to the expansion of knowledge of this important transcriptional......The transcriptional regulator GlxR has been characterized as a global hub within the gene-regulatory network of Corynebacterium glutamicum. Chromatin immunoprecipitation with a specific anti-GlxR antibody and subsequent high-throughput sequencing (ChIP-seq) was applied to C. glutamicum to get new...... mapping of these data on the genome sequence of C. glutamicum, 107 enriched DNA fragments were detected from cells grown with glucose as carbon source. GlxR binding sites were identified in the sequence of 79 enriched DNA fragments, of which 21 sites were not previously reported. Electrophoretic mobility...

  16. Flux through the tetrahydrodipicolinate succinylase pathway is dispensable for L-lysine production in Corynebacterium glutamicum.

    Science.gov (United States)

    Shaw-Reid, C A; McCormick, M M; Sinskey, A J; Stephanopoulos, G

    1999-03-01

    The N-succinyl-LL-diaminopimelate desuccinylase gene (dapE) in the four-step succinylase branch of the L-lysine biosynthetic pathway of Corynebacterium glutamicum was disrupted via marker-exchange mutagenesis to create a mutant strain that uses only the one-step meso-diaminopimelate dehydrogenase branch to overproduce lysine. This mutant strain grew and utilized glucose from minimal medium at the same rate as the parental strain. In addition, the dapE- strain produced lysine at the same rate as its parent strain. Transformation of the parental and dapE- strains with the amplified meso-diaminopimelate dehydrogenase gene (ddh) on a plasmid did not affect lysine production in either strain, despite an eightfold amplification of the activity of the enzyme. These results indicate that the four-step succinylase pathway is dispensable for lysine overproduction in shake-flask culture. In addition, the one-step meso-diaminopimelate dehydrogenase pathway does not limit lysine flux in Corynebacterium under these conditions.

  17. Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce l-Glutamic Acid Production▿

    OpenAIRE

    Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

    2007-01-01

    Corynebacterium glutamicum is a biotin auxotroph that secretes l-glutamic acid in response to biotin limitation; this process is employed in industrial l-glutamic acid production. Fatty acid ester surfactants and penicillin also induce l-glutamic acid secretion, even in the presence of biotin. However, the mechanism of l-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in l-gluta...

  18. In Vivo Roles of Fatty Acid Biosynthesis Enzymes in Biosynthesis of Biotin and α-Lipoic Acid in Corynebacterium glutamicum.

    Science.gov (United States)

    Ikeda, Masato; Nagashima, Takashi; Nakamura, Eri; Kato, Ryosuke; Ohshita, Masakazu; Hayashi, Mikiro; Takeno, Seiki

    2017-10-01

    For fatty acid biosynthesis, Corynebacterium glutamicum uses two type I fatty acid synthases (FAS-I), FasA and FasB, in addition to acetyl-coenzyme A (CoA) carboxylase (ACC) consisting of AccBC, AccD1, and AccE. The in vivo roles of the enzymes in supplying precursors for biotin and α-lipoic acid remain unclear. Here, we report genetic evidence demonstrating that the biosynthesis of these cofactors is linked to fatty acid biosynthesis through the FAS-I pathway. For this study, we used wild-type C. glutamicum and its derived biotin vitamer producer BFI-5, which was engineered to express Escherichia coli bioBF and Bacillus subtilis bioI Disruption of either fasA or fasB in strain BFI-5 led to decreased production of biotin vitamers, whereas its amplification contributed to increased production, with a larger impact of fasA in both cases. Double disruptions of fasA and fasB resulted in no biotin vitamer production. The acc genes showed a positive effect on production when amplified simultaneously. Augmented fatty acid biosynthesis was also reflected in pimelic acid production when carbon flow was blocked at the BioF reaction. These results indicate that carbon flow down the FAS-I pathway is destined for channeling into the biotin biosynthesis pathway, and that FasA in particular has a significant impact on precursor supply. In contrast, fasB disruption resulted in auxotrophy for lipoic acid or its precursor octanoic acid in both wild-type and BFI-5 strains. The phenotypes were fully complemented by plasmid-mediated expression of fasB but not fasA These results reveal that FasB plays a specific physiological role in lipoic acid biosynthesis in C. glutamicum IMPORTANCE For the de novo biosynthesis of fatty acids, C. glutamicum exceptionally uses a eukaryotic multifunctional type I fatty acid synthase (FAS-I) system comprising FasA and FasB, in contrast to most bacteria, such as E. coli and B. subtilis , which use an individual nonaggregating type II fatty acid synthase

  19. Characterization and chromosomal organization of the murD-murC-ftsQ region of Corynebacterium glutamicum ATCC 13869.

    Science.gov (United States)

    Ramos, Angelina; Honrubia, Maria P; Vega, Daniel; Ayala, Juan A; Bouhss, Ahmed; Mengin-Lecreulx, Dominique; Gil, José A

    2004-04-01

    The sequence of a 4.6-kb region of DNA from Corynebacterium glutamicum ATCC 13869 lying upstream from the ftsQ-ftsZ region has been determined. The region contains four genes with high similarity to the murD, ftsW, murG, and murC genes from different microorganisms. The products of these mur genes probably catalyse several steps in the formation of the precursors for peptidoglycan synthesis in C. glutamicum, whereas ftsW might play also a role in the stabilisation of the FtsZ ring during cell division. The murC gene product was purified to near homogeneity and its UDP-N-acetylmuramate: L-alanine adding activity was demonstrated. Northern analysis indicated that ftsW, murG and ftsQ are poorly expressed in C. glutamicum whereas murC and ftsZ are expressed at higher levels at the beginning of the exponential phase. Dicistronic (ftsQ-ftsZ) and monocistronic (murC and ftsZ) transcripts can be detected using specific probes and are in agreement with the lack of transcriptional terminators in the partially analysed dcw cluster. Disruption experiments performed in C. glutamicum using internal fragments of the ftsW, murG and murC genes allowed us to conclude that FtsW, MurG, and MurC are essential gene products in C. glutamicum.

  20. A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress.

    Directory of Open Access Journals (Sweden)

    Tao Su

    Full Text Available Peroxiredoxin Q (PrxQ that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions. Accordingly, PrxQ-mediated resistance to adverse stresses mainly relied on the degradation of ROS. The physiological roles of PrxQ in resistance to adverse stresses were corroborated by its induced expression under adverse stresses, regulated directly by the stress-responsive ECF-sigma factor SigH. Through catalytical kinetic activity, heterodimer formation, and bacterial two-hybrid analysis, we proved that C. glutamicum PrxQ catalytically eliminated peroxides by exclusively receiving electrons from thioredoxin (Trx/thioredoxin reductase (TrxR system and had a broad range of oxidizing substrates, but a better efficiency for peroxynitrite and cumene hydroperoxide (CHP. Site-directed mutagenesis confirmed that the conserved Cys49 and Cys54 are the peroxide oxidation site and the resolving Cys residue, respectively. It was also discovered that C. glutamicum PrxQ mainly existed in monomer whether under its native state or functional state. Based on these results, a catalytic model of PrxQ is being proposed. Moreover, our result that C. glutamicum PrxQ can prevent the damaging effects of adverse stresses by acting as thioredoxin-dependent monomeric peroxidase could be further applied to improve the survival ability and robustness of the important bacterium during fermentation process.

  1. Optimization of the IPP Precursor Supply for the Production of Lycopene, Decaprenoxanthin and Astaxanthin by Corynebacterium glutamicum

    International Nuclear Information System (INIS)

    Heider, Sabine A. E.; Wolf, Natalie; Hofemeier, Arne; Peters-Wendisch, Petra; Wendisch, Volker F.

    2014-01-01

    The biotechnologically relevant bacterium Corynebacterium glutamicum, currently used for the million ton-scale production of amino acids for the food and feed industries, is pigmented due to synthesis of the rare cyclic C50 carotenoid decaprenoxanthin and its glucosides. The precursors of carotenoid biosynthesis, isopenthenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate, are synthesized in this organism via the methylerythritol phosphate (MEP) or non-mevalonate pathway. Terminal pathway engineering in recombinant C. glutamicum permitted the production of various non-native C50 and C40 carotenoids. Here, the role of engineering isoprenoid precursor supply for lycopene production by C. glutamicum was characterized. Overexpression of dxs encoding the enzyme that catalyzes the first committed step of the MEP-pathway by chromosomal promoter exchange in a prophage-cured, genome-reduced C. glutamicum strain improved lycopene formation. Similarly, an increased IPP supply was achieved by chromosomal integration of two artificial operons comprising MEP pathway genes under the control of a constitutive promoter. Combined overexpression of dxs and the other six MEP pathways genes in C. glutamicum strain LYC3-MEP was not synergistic with respect to improving lycopene accumulation. Based on C. glutamicum strain LYC3-MEP, astaxanthin could be produced in the milligrams per gram cell dry weight range when the endogenous genes crtE, crtB, and crtI for conversion of geranylgeranyl pyrophosphate to lycopene were coexpressed with the genes for lycopene cyclase and β-carotene hydroxylase from Pantoea ananatis and carotene C(4) oxygenase from Brevundimonas aurantiaca.

  2. Physico-chemical parameter for production of lactic acid or ethanol of (corynebacterium glutamicum) bacteria

    International Nuclear Information System (INIS)

    Castellanos, Angelica; Garcia, Lina Marcela; Astudillo, Myriam; Lopez Galan, Jorge Enrique; Florez Pardo, Luz Marina.

    2011-01-01

    The interest to obtain products for the bio-fuel industry from renewable resources has directed research to find resistant and costs-effective biotechnological systems. Corynebacterium glutamicum, is a microorganism used to produce amino acids, that grows in wide variety of substrates and its resistance during fermentation to pH, temperature, osmotic pressure variations and alcohol aggregate, renders this organism a suitable candidate to improve by genetic modifications lactic acid and ethanol synthesis. However, some aspects of its physiology remain unknown, such us increase lactic acid and ethanol production from C5 and C6 sugars. For this reason, the main aim in our work was to identify the most important variables with impact on culture and the best culture conditions to produce lactic acid or ethanol in batch culture. To achieve this objective, eight variables were tested in culture using a statistical model. The best culture conditions were obtained and tested in a bacth bioreactor system. Temperature, biotin and glucose concentration were the variables with most impact (p - 1 , 16 g/l of lactic acid was obtained after 15 h of culture with an efficiency of 32%. High glucose consumption was observed during bacterial growth, which leads to low concentration of substrate for the production process; this suggests a culture feeding at the end of exponential growth phase, which can increase the production yield.

  3. Mutational analysis to identify the residues essential for the inhibition of N-acetyl glutamate kinase of Corynebacterium glutamicum.

    Science.gov (United States)

    Huang, Yuanyuan; Zhang, Hao; Tian, Hongming; Li, Cheng; Han, Shuangyan; Lin, Ying; Zheng, Suiping

    2015-09-01

    N-acetyl glutamate kinase (NAGK) is a key enzyme in the synthesis of L-arginine that is inhibited by its end product L-arginine in Corynebacterium glutamicum (C. glutamicum). In this study, the potential binding sites of arginine and the residues essential for its inhibition were identified by homology modeling, inhibitor docking, and site-directed mutagenesis. The allosteric inhibition of NAGK was successfully alleviated by a mutation, as determined through analysis of mutant enzymes, which were overexpressed in vivo in C. glutamicum ATCC14067. Analysis of the mutant enzymes and docking analysis demonstrated that residue W23 positions an arginine molecule, and the interaction between arginine and residues L282, L283, and T284 may play an important role in the remote inhibitory process. Based on the results of the docking analysis of the effective mutants, we propose a linkage mechanism for the remote allosteric regulation of NAGK activity, in which residue R209 may play an essential role. In this study, the structure of the arginine-binding site of C. glutamicum NAGK (CgNAGK) was successfully predicted and the roles of the relevant residues were identified, providing new insight into the allosteric regulation of CgNAGK activity and a solid platform for the future construction of an optimized L-arginine producing strain.

  4. Lactate production as representative of the fermentation potential of Corynebacterium glutamicum 2262 in a one-step process.

    Science.gov (United States)

    Khuat, Hoang Bao Truc; Kaboré, Abdoul Karim; Olmos, Eric; Fick, Michel; Boudrant, Joseph; Goergen, Jean-Louis; Delaunay, Stéphane; Guedon, Emmanuel

    2014-01-01

    The fermentative properties of thermo-sensitive strain Corynebacterium glutamicum 2262 were investigated in processes coupling aerobic cell growth and the anaerobic fermentation phase. In particular, the influence of two modes of fermentation on the production of lactate, the fermentation product model, was studied. In both processes, lactate was produced in significant amount, 27 g/L in batch culture, and up to 55.8 g/L in fed-batch culture, but the specific production rate in the fed-batch culture was four times lower than that in the batch culture. Compared to other investigated fermentation processes, our strategy resulted in the highest yield of lactic acid from biomass. Lactate production by C. glutamicum 2262 thus revealed the capability of the strain to produce various fermentation products from pyruvate.

  5. Osmolality, temperature, and membrane lipid composition modulate the activity of betaine transporter BetP in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Ozcan, Nuran; Ejsing, Christer S.; Shevchenko, Andrej

    2007-01-01

    The gram-positive soil bacterium Corynebacterium glutamicum, a major amino acid-producing microorganism in biotechnology, is equipped with several osmoregulated uptake systems for compatible solutes, which is relevant for the physiological response to osmotic stress. The most significant carrier......P activity. We further correlated the change in BetP regulation properties in cells grown at different temperatures to changes in the lipid composition of the plasma membrane. For this purpose, the glycerophospholipidome of C. glutamicum grown at different temperatures was analyzed by mass spectrometry using...... quantitative multiple precursor ion scanning. The molecular composition of glycerophospholipids was strongly affected by the growth temperature. The modulating influence of membrane lipid composition on BetP function was further corroborated by studying the influence of artificial modulation of membrane...

  6. Effect of biotin on transcription levels of key enzymes and glutamate efflux in glutamate fermentation by Corynebacterium glutamicum.

    Science.gov (United States)

    Cao, Yan; Duan, Zuoying; Shi, Zhongping

    2014-02-01

    Biotin is an important factor affecting the performance of glutamate fermentation by biotin auxotrophic Corynebacterium glutamicum and glutamate is over-produced only when initial biotin content is controlled at suitable levels or initial biotin is excessive but with Tween 40 addition during fermentation. The transcription levels of key enzymes at pyruvate, isocitrate and α-ketoglutarate metabolic nodes, as well as transport protein (TP) of glutamate were investigated under the conditions of varied biotin contents and Tween 40 supplementation. When biotin was insufficient, the genes encoding key enzymes and TP were down-regulated in the early production phase, in particular, the transcription level of isocitrate dehydrogenase (ICDH) which was only 2% of that of control. Although the cells' morphology transformation and TP level were not affected, low transcription level of ICDH led to lower final glutamate concentration (64 g/L). When biotin was excessive, the transcription levels of key enzymes were at comparable levels as those of control with ICDH as an exception, which was only 3-22% of control level throughout production phase. In this case, little intracellular glutamate accumulation (1.5 mg/g DCW) and impermeable membrane resulted in non glutamate secretion into broth, even though the quantity of TP was more than 10-folds of control level. Addition of Tween 40 when biotin was excessive stimulated the expression of all key enzymes and TP, intracellular glutamate content was much higher (10-12 mg/g DCW), and final glutamate concentration reached control level (75-80 g/L). Hence, the membrane alteration and TP were indispensable in glutamate secretion. Biotin and Tween 40 influenced the expression level of ICDH and glutamate efflux, thereby influencing glutamate production.

  7. Biosynthesis of rare ketoses through constructing a recombination pathway in an engineered Corynebacterium glutamicum.

    Science.gov (United States)

    Yang, Jiangang; Zhu, Yueming; Li, Jitao; Men, Yan; Sun, Yuanxia; Ma, Yanhe

    2015-01-01

    Rare sugars have various known biological functions and potential for applications in pharmaceutical, cosmetics, and food industries. Here we designed and constructed a recombination pathway in Corynebacterium glutamicum, in which dihydroxyacetone phosphate (DHAP), an intermediate of the glycolytic pathway, and a variety of aldehydes were condensed to synthesize rare ketoses sequentially by rhamnulose-1-phosphate aldolase (RhaD) and fructose-1-phosphatase (YqaB) obtained from Escherichia coli. A wild-type strain harboring this artificial pathway had the ability to produce D-sorbose and D-psicose using D-glyceraldehyde and glucose as the substrates. The tpi gene, encoding triose phosphate isomerase was further deleted, and the concentration of DHAP increased to nearly 20-fold relative to that of the wild-type. After additional optimization of expression levels from rhaD and yqaB genes and of the fermentation conditions, the engineered strain SY6(pVRTY) exhibited preferable performance for rare ketoses production. Its yield increased to 0.59 mol/mol D-glyceraldehyde from 0.33 mol/mol D-glyceraldehyde and productivity to 2.35 g/L h from 0.58 g/L h. Moreover, this strain accumulated 19.5 g/L of D-sorbose and 13.4 g/L of D-psicose using a fed-batch culture mode under the optimal conditions. In addition, it was verified that the strain SY6(pVRTY) meanwhile had the ability to synthesize C4, C5, C6, and C7 rare ketoses when a range of representative achiral and homochiral aldehydes were applied as the substrates. Therefore, the platform strain exhibited the potential for microbial production of rare ketoses and deoxysugars. © 2014 Wiley Periodicals, Inc.

  8. Selection and Characterization of a Lysine Yielding Mutant of Corynebacterium glutamicum - a Soil Isolate from Pakistan

    Directory of Open Access Journals (Sweden)

    Habib-ur-Rehman§٭, Abdul Hameed and Safia Ahmed

    2012-01-01

    Full Text Available L-lysine is the second limiting amino acid for poultry and supplemented in broiler feed for optimal performance. Lysine can be produced by inducing mutation in glutamate producing bacteria. The study was conducted to enhance lysine production from a local strain of Corynebacterium glutamicum. The bacterium was mutated by exposure to UV. Mutants resistant to s-2-aminoethyle L-cystein (AEC and showing auxotrophy for L-homoserine were screened for lysine production qualitatively and quantitatively. A mutant showing highest production of lysine (8.2 mg/mL was selected for optimization of physical and nutritional parameters for maximum production of lysine in shake flask. An initial pH 7.6, 30˚C temperature, 300 rpm and 60 h incubation time were the optimized values of physical requirements. Cane molasses and corn starch hydrolysate were required at 15% (w/v in the fermentation media which provided around 9% total sugars to produce maximum lysine (17 to 18 mg/mL. When amonium sulphate was used at 3.5% (w/v level in molasses or corn starch hydrolysate based fermentation media, production of lysine slightly increased above 18 mg/mL. It is concluded that industrial by products like cane molasses, corn steep liquor, and corn starch hydrolysate can be used as carbon and organic nitrogen sources in fermentation medium for scale up process of lysine production and this lysine enriched broth may be used in broiler feed later. However, more potent lysine producing mutant and additional in vivo trials would be required to commercialize this product.

  9. Boosting Anaplerotic Reactions by Pyruvate Kinase Gene Deletion and Phosphoenolpyruvate Carboxylase Desensitization for Glutamic Acid and Lysine Production in Corynebacterium glutamicum.

    Science.gov (United States)

    Yokota, Atsushi; Sawada, Kazunori; Wada, Masaru

    In the 1980s, Shiio and coworkers demonstrated using random mutagenesis that the following three phenotypes were effective for boosting lysine production by Corynebacterium glutamicum: (1) low-activity-level citrate synthase (CS L ), (2) phosphoenolpyruvate carboxylase (PEPC) resistant to feedback inhibition by aspartic acid (PEPC R ), and (3) pyruvate kinase (PYK) deficiency. Here, we reevaluated these phenotypes and their interrelationship in lysine production using recombinant DNA techniques.The pyk deletion and PEPC R (D299N in ppc) independently showed marginal effects on lysine production, but both phenotypes synergistically increased lysine yield, demonstrating the importance of PEPC as an anaplerotic enzyme in lysine production. Similar effects were also found for glutamic acid production. CS L (S252C in gltA) further increased lysine yield. Thus, using molecular techniques, the combination of these three phenotypes was reconfirmed to be effective for lysine production. However, a simple CS L mutant showed instabilities in growth and lysine yield.Surprisingly, the pyk deletion was found to increase biomass production in wild-type C. glutamicum ATCC13032 under biotin-sufficient conditions. The mutant showed a 37% increase in growth (based on OD 660 ) compared with the ATCC13032 strain in a complex medium containing 100 g/L glucose. Metabolome analysis revealed the intracellular accumulation of excess precursor metabolites. Thus, their conversion into biomass was considered to relieve the metabolic distortion in the pyk-deleted mutant. Detailed physiological studies of various pyk-deleted mutants also suggested that malate:quinone oxidoreductase (MQO) is important to control both the intracellular oxaloacetic acid (OAA) level and respiration rate. These findings may facilitate the rational use of C. glutamicum in fermentation industries.

  10. Functional analysis of sequences adjacent to dapE of Corynebacterium glutamicum reveals the presence of aroP, which encodes the aromatic amino acid transporter.

    Science.gov (United States)

    Wehrmann, A; Morakkabati, S; Krämer, R; Sahm, H; Eggeling, L

    1995-10-01

    An initially nonclonable DNA locus close to a gene of L-lysine biosynthesis in Corynebacterium glutamicum was analyzed in detail. Its stepwise cloning and its functional identification by monitoring the amino acid uptakes of defined mutants, together with mechanistic studies, identified the corresponding structure as aroP, the general aromatic amino acid uptake system.

  11. Disruption of pknG enhances production of gamma-aminobutyric acid by Corynebacterium glutamicum expressing glutamate decarboxylase.

    Science.gov (United States)

    Okai, Naoko; Takahashi, Chihiro; Hatada, Kazuki; Ogino, Chiaki; Kondo, Akihiko

    2014-01-01

    Gamma-aminobutyric acid (GABA), a building block of the biodegradable plastic polyamide 4, is synthesized from glucose by Corynebacterium glutamicum that expresses Escherichia coli glutamate decarboxylase (GAD) B encoded by gadB. This strain was engineered to produce GABA more efficiently from biomass-derived sugars. To enhance GABA production further by increasing the intracellular concentration of its precursor glutamate, we focused on engineering pknG (encoding serine/threonine protein kinase G), which controls the activity of 2-oxoglutarate dehydrogenase (Odh) in the tricarboxylic acid cycle branch point leading to glutamate synthesis. We succeeded in expressing GadB in a C. glutamicum strain harboring a deletion of pknG. C. glutamicum strains GAD and GAD ∆pknG were cultured in GP2 medium containing 100 g L(-1) glucose and 0.1 mM pyridoxal 5'-phosphate. Strain GAD∆pknG produced 31.1 ± 0.41 g L(-1) (0.259 g L(-1) h(-1)) of GABA in 120 hours, representing a 2.29-fold higher level compared with GAD. The production yield of GABA from glucose by GAD∆pknG reached 0.893 mol mol(-1).

  12. A de novo NADPH generation pathway for improving lysine production of Corynebacterium glutamicum by rational design of the coenzyme specificity of glyceraldehyde 3-phosphate dehydrogenase.

    Science.gov (United States)

    Bommareddy, Rajesh Reddy; Chen, Zhen; Rappert, Sugima; Zeng, An-Ping

    2014-09-01

    Engineering the cofactor availability is a common strategy of metabolic engineering to improve the production of many industrially important compounds. In this work, a de novo NADPH generation pathway is proposed by altering the coenzyme specificity of a native NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) to NADP, which consequently has the potential to produce additional NADPH in the glycolytic pathway. Specifically, the coenzyme specificity of GAPDH of Corynebacterium glutamicum is systematically manipulated by rational protein design and the effect of the manipulation for cellular metabolism and lysine production is evaluated. By a combinatorial modification of four key residues within the coenzyme binding sites, different GAPDH mutants with varied coenzyme specificity were constructed. While increasing the catalytic efficiency of GAPDH towards NADP enhanced lysine production in all of the tested mutants, the most significant improvement of lysine production (~60%) was achieved with the mutant showing similar preference towards both NAD and NADP. Metabolic flux analysis with (13)C isotope studies confirmed that there was no significant change of flux towards the pentose phosphate pathway and the increased lysine yield was mainly attributed to the NADPH generated by the mutated GAPDH. The present study highlights the importance of protein engineering as a key strategy in de novo pathway design and overproduction of desired products. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  13. Quinone-dependent D-lactate dehydrogenase Dld (Cg1027 is essential for growth of Corynebacterium glutamicum on D-lactate

    Directory of Open Access Journals (Sweden)

    Oikawa Tadao

    2010-12-01

    Full Text Available Abstract Background Corynebacterium glutamicum is able to grow with lactate as sole or combined carbon and energy source. Quinone-dependent L-lactate dehydrogenase LldD is known to be essential for utilization of L-lactate by C. glutamicum. D-lactate also serves as sole carbon source for C. glutamicum ATCC 13032. Results Here, the gene cg1027 was shown to encode the quinone-dependent D-lactate dehydrogenase (Dld by enzymatic analysis of the protein purified from recombinant E. coli. The absorption spectrum of purified Dld indicated the presence of FAD as bound cofactor. Inactivation of dld resulted in the loss of the ability to grow with D-lactate, which could be restored by plasmid-borne expression of dld. Heterologous expression of dld from C. glutamicum ATCC 13032 in C. efficiens enabled this species to grow with D-lactate as sole carbon source. Homologs of dld of C. glutamicum ATCC 13032 are not encoded in the sequenced genomes of other corynebacteria and mycobacteria. However, the dld locus of C. glutamicum ATCC 13032 shares 2367 bp of 2372 bp identical nucleotides with the dld locus of Propionibacterium freudenreichii subsp. shermanii, a bacterium used in Swiss-type cheese making. Both loci are flanked by insertion sequences of the same family suggesting a possible event of horizontal gene transfer. Conclusions Cg1067 encodes quinone-dependent D-lactate dehydrogenase Dld of Corynebacterium glutamicum. Dld is essential for growth with D-lactate as sole carbon source. The genomic region of dld likely has been acquired by horizontal gene transfer.

  14. Rich biotin content in lignocellulose biomass plays the key role in determining cellulosic glutamic acid accumulation by Corynebacterium glutamicum.

    Science.gov (United States)

    Wen, Jingbai; Xiao, Yanqiu; Liu, Ting; Gao, Qiuqiang; Bao, Jie

    2018-01-01

    Lignocellulose is one of the most promising alternative feedstocks for glutamic acid production as commodity building block chemical, but the efforts by the dominant industrial fermentation strain Corynebacterium glutamicum failed for accumulating glutamic acid using lignocellulose feedstock. We identified the existence of surprisingly high biotin concentration in corn stover hydrolysate as the determining factor for the failure of glutamic acid accumulation by Corynebacterium glutamicum . Under excessive biotin content, induction by penicillin resulted in 41.7 ± 0.1 g/L of glutamic acid with the yield of 0.50 g glutamic acid/g glucose. Our further investigation revealed that corn stover contained 353 ± 16 μg of biotin per kg dry solids, approximately one order of magnitude greater than the biotin in corn grain. Most of the biotin remained stable during the biorefining chain and the rich biotin content in corn stover hydrolysate almost completely blocked the glutamic acid accumulation. This rich biotin existence was found to be a common phenomenon in the wide range of lignocellulose biomass and this may be the key reason why the previous studies failed in cellulosic glutamic acid fermentation from lignocellulose biomass. The extended recording of the complete members of all eight vitamin B compounds in lignocellulose biomass further reveals that the major vitamin B members were also under the high concentration levels even after harsh pretreatment. The high content of biotin in wide range of lignocellulose biomass feedstocks and the corresponding hydrolysates was discovered and it was found to be the key factor in determining the cellulosic glutamic acid accumulation. The highly reserved biotin and the high content of their other vitamin B compounds in biorefining process might act as the potential nutrients to biorefining fermentations. This study creates a new insight that lignocellulose biorefining not only generates inhibitors, but also keeps nutrients

  15. Characterization of the biotin uptake system encoded by the biotin-inducible bioYMN operon of Corynebacterium glutamicum

    Science.gov (United States)

    2012-01-01

    Background The amino acid-producing Gram-positive Corynebacterium glutamicum is auxotrophic for biotin although biotin ring assembly starting from the precursor pimeloyl-CoA is still functional. It possesses AccBC, the α-subunit of the acyl-carboxylases involved in fatty acid and mycolic acid synthesis, and pyruvate carboxylase as the only biotin-containing proteins. Comparative genome analyses suggested that the putative transport system BioYMN encoded by cg2147, cg2148 and cg2149 might be involved in biotin uptake by C. glutamicum. Results By comparison of global gene expression patterns of cells grown with limiting or excess supply of biotin or with dethiobiotin as supplement replacing biotin revealed that expression of genes coding for enzymes of biotin ring assembly and for the putative uptake system was regulated according to biotin availability. RT-PCR and 5'-RACE experiments demonstrated that the genes bioY, bioM, and bioN are transcribed from one promoter as a single transcript. Biochemical analyses revealed that BioYMN catalyzes the effective uptake of biotin with a concentration of 60 nM biotin supporting a half-maximal transport rate. Maximal biotin uptake rates were at least five fold higher in biotin-limited cells as compared to cells grown with excess biotin. Overexpression of bioYMN led to an at least 50 fold higher biotin uptake rate as compared to the empty vector control. Overproduction of BioYMN alleviated biotin limitation and interfered with triggering L-glutamate production by biotin limitation. Conclusions The operon bioYMN from C. glutamicum was shown to be induced by biotin limitation. Transport assays with radio-labeled biotin revealed that BioYMN functions as a biotin uptake system. Overexpression of bioYMN affected L-glutamate production triggered by biotin limitation. PMID:22243621

  16. Characterization of the biotin uptake system encoded by the biotin-inducible bioYMN operon of Corynebacterium glutamicum.

    Science.gov (United States)

    Schneider, Jens; Peters-Wendisch, Petra; Stansen, K Corinna; Götker, Susanne; Maximow, Stanislav; Krämer, Reinhard; Wendisch, Volker F

    2012-01-13

    The amino acid-producing Gram-positive Corynebacterium glutamicum is auxotrophic for biotin although biotin ring assembly starting from the precursor pimeloyl-CoA is still functional. It possesses AccBC, the α-subunit of the acyl-carboxylases involved in fatty acid and mycolic acid synthesis, and pyruvate carboxylase as the only biotin-containing proteins. Comparative genome analyses suggested that the putative transport system BioYMN encoded by cg2147, cg2148 and cg2149 might be involved in biotin uptake by C. glutamicum. By comparison of global gene expression patterns of cells grown with limiting or excess supply of biotin or with dethiobiotin as supplement replacing biotin revealed that expression of genes coding for enzymes of biotin ring assembly and for the putative uptake system was regulated according to biotin availability. RT-PCR and 5'-RACE experiments demonstrated that the genes bioY, bioM, and bioN are transcribed from one promoter as a single transcript. Biochemical analyses revealed that BioYMN catalyzes the effective uptake of biotin with a concentration of 60 nM biotin supporting a half-maximal transport rate. Maximal biotin uptake rates were at least five fold higher in biotin-limited cells as compared to cells grown with excess biotin. Overexpression of bioYMN led to an at least 50 fold higher biotin uptake rate as compared to the empty vector control. Overproduction of BioYMN alleviated biotin limitation and interfered with triggering L-glutamate production by biotin limitation. The operon bioYMN from C. glutamicum was shown to be induced by biotin limitation. Transport assays with radio-labeled biotin revealed that BioYMN functions as a biotin uptake system. Overexpression of bioYMN affected L-glutamate production triggered by biotin limitation.

  17. Different modes of diaminopimelate synthesis and their role in cell wall integrity: a study with Corynebacterium glutamicum.

    Science.gov (United States)

    Wehrmann, A; Phillipp, B; Sahm, H; Eggeling, L

    1998-06-01

    In eubacteria, there are three slightly different pathways for the synthesis of m-diaminopimelate (m-DAP), which is one of the key linking units of peptidoglycan. Surprisingly, for unknown reasons, some bacteria use two of these pathways together. An example is Corynebacterium glutamicum, which uses both the succinylase and dehydrogenase pathways for m-DAP synthesis. In this study, we clone dapD and prove by enzyme experiments that this gene encodes the succinylase (M(r) = 24082), initiating the succinylase pathway of m-DAP synthesis. By using gene-directed mutation, dapD, as well as dapE encoding the desuccinylase, was inactivated, thereby forcing C. glutamicum to use only the dehydrogenase pathway of m-DAP synthesis. The mutants are unable to grow on organic nitrogen sources. When supplied with low ammonium concentrations but excess carbon, their morphology is radically altered and they are less resistant to mechanical stress than the wild type. Since the succinylase has a high affinity toward its substrate and uses glutamate as the nitrogen donor, while the dehydrogenase has a low affinity and incorporates ammonium directly, the m-DAP synthesis is another example of twin activities present in bacteria for access to important metabolites such as the well-known twin activities for the synthesis of glutamate or for the uptake of potassium.

  18. Production of carbon-13-labeled cadaverine by engineered Corynebacterium glutamicum using carbon-13-labeled methanol as co-substrate.

    Science.gov (United States)

    Leßmeier, Lennart; Pfeifenschneider, Johannes; Carnicer, Marc; Heux, Stephanie; Portais, Jean-Charles; Wendisch, Volker F

    2015-12-01

    Methanol, a one-carbon compound, can be utilized by a variety of bacteria and other organisms as carbon and energy source and is regarded as a promising substrate for biotechnological production. In this study, a strain of non-methylotrophic Corynebacterium glutamicum, which was able to produce the polyamide building block cadaverine as non-native product, was engineered for co-utilization of methanol. Expression of the gene encoding NAD+-dependent methanol dehydrogenase (Mdh) from the natural methylotroph Bacillus methanolicus increased methanol oxidation. Deletion of the endogenous aldehyde dehydrogenase genes ald and fadH prevented methanol oxidation to carbon dioxide and formaldehyde detoxification via the linear formaldehyde dissimilation pathway. Heterologous expression of genes for the key enzymes hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase of the ribulose monophosphate (RuMP) pathway in this strain restored growth in the presence of methanol or formaldehyde, which suggested efficient formaldehyde detoxification involving RuMP key enzymes. While growth with methanol as sole carbon source was not observed, the fate of 13C-methanol added as co-substrate to sugars was followed and the isotopologue distribution indicated incorporation into central metabolites and in vivo activity of the RuMP pathway. In addition, 13C-label from methanol was traced to the secreted product cadaverine. Thus, this synthetic biology approach led to a C. glutamicum strain that converted the non-natural carbon substrate methanol at least partially to the non-native product cadaverine.

  19. The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors.

    Directory of Open Access Journals (Sweden)

    Philip D Townsend

    Full Text Available The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition.

  20. Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum.

    Science.gov (United States)

    Wang, Zhihao; Chan, Siu Hung Joshua; Sudarsan, Suresh; Blank, Lars M; Jensen, Peter Ruhdal; Solem, Christian

    2016-11-01

    The performance of Corynebacterium glutamicum cell factories producing compounds which rely heavily on NADPH has been reported to depend on the sugar being metabolized. While some aspects of this phenomenon have been elucidated, there are still many unresolved questions as to how sugar metabolism is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon. Initially, we found that a strain where the dedicated fructose uptake system had been inactivated (KO-ptsF) was hampered in growth on sucrose minimal medium, and suppressor mutants appeared readily. Comparative genomic analysis in conjunction with enzymatic assays revealed that suppression was linked to inactivation of the pfkB gene, encoding a fructose-1-phosphate kinase. Detailed characterization of KO-ptsF, KO-pfkB and double knock-out (DKO) derivatives revealed a strong role for sugar-phosphates, especially fructose-1-phosphate (F1P), in governing sugar as well as redox metabolism due to effects on transcriptional regulation of key genes. These findings allowed us to propose a simple model explaining the correlation between sugar phosphate concentration, gene expression and ultimately the observed phenotype. To guide us in our analysis and help us identify bottlenecks in metabolism we debugged an existing genome-scale model onto which we overlaid the transcriptome data. Based on the results obtained we managed to enhance the NADPH supply and transform the wild-type strain into delivering the highest yield of lysine ever obtained on sucrose and fructose, thus providing a good example of how regulatory mechanisms can be harnessed for bioproduction. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  1. Production of L-glutamic Acid with Corynebacterium glutamicum (NCIM 2168) and Pseudomonas reptilivora (NCIM 2598): A Study on Immobilization and Reusability.

    Science.gov (United States)

    Shyamkumar, Rajaram; Moorthy, Innasi Muthu Ganesh; Ponmurugan, Karuppiah; Baskar, Rajoo

    2014-07-01

    L-glutamic acid is one of the major amino acids that is present in a wide variety of foods. It is mainly used as a food additive and flavor enhancer in the form of sodium salt. Corynebacterium glutamicum (C. glutamicum) is one of the major organisms widely used for glutamic acid production. The study was dealing with immobilization of C. glutamicum and mixed culture of C. glutamicum and Pseudomonas reptilivora (P. reptilivora) for L-glutamic acid production using submerged fermentation. 2, 3 and 5% sodium alginate concentrations were used for production and reusability of immobilized cells for 5 more trials. The results revealed that 2% sodium alginate concentration produced the highest yield (13.026±0.247 g/l by C. glutamicum and 16.026±0.475 g/l by mixed immobilized culture). Moreover, reusability of immobilized cells was evaluated in 2% concentration with 5 more trials. However, when the number of cycles increased, the production of L-glutamic acid decreased. Production of glutamic acid using optimized medium minimizes the time needed for designing the medium composition. It also minimizes external contamination. Glutamic acid production gradually decreased due to multiple uses of beads and consequently it reduces the shelf life.

  2. Analysis of SOS-Induced Spontaneous Prophage Induction in Corynebacterium glutamicum at the Single-Cell Level

    Science.gov (United States)

    Nanda, Arun M.; Heyer, Antonia; Krämer, Christina; Grünberger, Alexander; Kohlheyer, Dietrich

    2014-01-01

    The genome of the Gram-positive soil bacterium Corynebacterium glutamicum ATCC 13032 contains three integrated prophage elements (CGP1 to -3). Recently, it was shown that the large lysogenic prophage CGP3 (∼187 kbp) is excised spontaneously in a small number of cells. In this study, we provide evidence that a spontaneously induced SOS response is partly responsible for the observed spontaneous CGP3 induction. Whereas previous studies focused mainly on the induction of prophages at the population level, we analyzed the spontaneous CGP3 induction at the single-cell level using promoters of phage genes (Pint2 and Plysin) fused to reporter genes encoding fluorescent proteins. Flow-cytometric analysis revealed a spontaneous CGP3 activity in about 0.01 to 0.08% of the cells grown in standard minimal medium, which displayed a significantly reduced viability. A PrecA-eyfp promoter fusion revealed that a small fraction of C. glutamicum cells (∼0.2%) exhibited a spontaneous induction of the SOS response. Correlation of PrecA to the activity of downstream SOS genes (PdivS and PrecN) confirmed a bona fide induction of this stress response rather than stochastic gene expression. Interestingly, the reporter output of PrecA and CGP3 promoter fusions displayed a positive correlation at the single-cell level (ρ = 0.44 to 0.77). Furthermore, analysis of the PrecA-eyfp/Pint2-e2-crimson strain during growth revealed the highest percentage of spontaneous PrecA and Pint2 activity in the early exponential phase, when fast replication occurs. Based on these studies, we postulate that spontaneously occurring DNA damage induces the SOS response, which in turn triggers the induction of lysogenic prophages. PMID:24163339

  3. Plasmid Vectors for Testing In Vivo Promoter Activities in Corynebacterium glutamicum and Rhodococcus erythropolis

    Czech Academy of Sciences Publication Activity Database

    Knoppová, Monika; Phensaijai, M.; Veselý, Martin; Zemanová, Martina; Nešvera, Jan; Pátek, Miroslav

    2007-01-01

    Roč. 55, - (2007), s. 234-239 ISSN 0343-8651 R&D Projects: GA ČR GA526/04/0542; GA ČR GA204/06/0330 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium * rhodoccoccus * promoter-probe vectors Subject RIV: EE - Microbiology , Virology Impact factor: 1.167, year: 2007

  4. The role of lipids and salts in two-dimensional crystallization of the glycine-betaine transporter BetP from Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Tsai, Ching-Ju; Ejsing, Christer S.; Shevchenko, Andrej

    2007-01-01

    The osmoregulated and chill-sensitive glycine-betaine transporter (BetP) from Corynebacterium glutamicum was reconstituted into lipids to form two-dimensional (2D) crystals. The sensitivity of BetP partly bases on its interaction with lipids. Here we demonstrate that lipids and salts influence...... crystal morphology and crystallinity of a C-terminally truncated BetP. The salt type and concentration during crystallization determined whether crystals grew in the form of planar-tubes, sheets or vesicles, while the lipid type influenced crystal packing and order. Three different lipid preparations...... for 2D crystallization were compared. Only the use of lipids extracted from C. glutamicum cells led to the formation of large, well-ordered crystalline areas. To understand the lipid-derived influence on crystallinity, lipid extracts from different stages of the crystallization process were analyzed...

  5. The two-component signal transduction system CopRS of Corynebacterium glutamicum is required for adaptation to copper-excess stress

    OpenAIRE

    Schelder, S.; Zaade, D.; Litsanov, B.; Bott, M.; Brocker, M.

    2011-01-01

    Copper is an essential cofactor for many enzymes but at high concentrations it is toxic for the cell. Copper ion concentrations ≥50 µM inhibited growth of Corynebacterium glutamicum. The transcriptional response to 20 µM Cu(2+) was studied using DNA microarrays and revealed 20 genes that showed a ≥ 3-fold increased mRNA level, including cg3281-cg3289. Several genes in this genomic region code for proteins presumably involved in the adaption to copper-induced stress, e. g. a multicopper oxidas...

  6. Chassis organism from Corynebacterium glutamicum--a top-down approach to identify and delete irrelevant gene clusters.

    Science.gov (United States)

    Unthan, Simon; Baumgart, Meike; Radek, Andreas; Herbst, Marius; Siebert, Daniel; Brühl, Natalie; Bartsch, Anna; Bott, Michael; Wiechert, Wolfgang; Marin, Kay; Hans, Stephan; Krämer, Reinhard; Seibold, Gerd; Frunzke, Julia; Kalinowski, Jörn; Rückert, Christian; Wendisch, Volker F; Noack, Stephan

    2015-02-01

    For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application. © 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence, which permits use and distribution in any medium, provided the original work is properly cited, the use is non- commercial and no modifications or adaptations are made.

  7. Transcriptional Analysis of the groES-groEL1, groEL2, and dnaK genes in Corynebacterium glutamicum: Characterization of Heat Shock-Induced Promoters

    Czech Academy of Sciences Publication Activity Database

    Barreiro, C.; González-Lavado, E.; Pátek, Miroslav; Martin, J. F.

    2004-01-01

    Roč. 186, č. 14 (2004), s. 4813-4817 ISSN 0021-9193 R&D Projects: GA AV ČR KSK5052113 Keywords : corynebacterium glutamicum * mrna Subject RIV: EE - Microbiology, Virology Impact factor: 4.146, year: 2004

  8. Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum

    Czech Academy of Sciences Publication Activity Database

    Busche, T.; Šilar, Radoslav; Pičmanová, Martina; Pátek, Miroslav; Kalinowski, J.

    2012-01-01

    Roč. 13, č. 445 (2012), s. 445-464 ISSN 1471-2164 R&D Projects: GA ČR GC204/09/J015 Institutional research plan: CEZ:AV0Z50200510 Keywords : Corynebacterium glutamicum * ECF sigma factor * Anti-sigma factor Subject RIV: EE - Microbiology, Virology Impact factor: 4.397, year: 2012

  9. Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase to switch the nucleotide-cofactor specificity for increasing l-lysine production.

    Science.gov (United States)

    Xu, Jian-Zhong; Yang, Han-Kun; Liu, Li-Ming; Wang, Ying-Yu; Zhang, Wei-Guo

    2018-03-25

    l-lysine is an important amino acid in animals and humans and NADPH is a vital cofactor for maximizing the efficiency of l-lysine fermentation. Dihydrodipicolinate reductase (DHDPR), an NAD(P)H-dependent enzyme, shows a variance in nucleotide-cofactor affinity in bacteria. In this study, we rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its nucleotide-cofactor specificity resulting in an increase in final titer (from 82.6 to 117.3 g L -1 ), carbon yield (from 0.35 to 0.44 g [g glucose] -1 ) and productivity (from 2.07 to 2.93 g L -1  hr -1 ) of l-lysine in JL-6 ΔdapB::Ec-dapB C115G,G116C in fed-batch fermentation. To do this, we comparatively analyzed the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating that hetero-expression of NADH-dependent EcDHDPR increased l-lysine production. Subsequently, we rationally modified the conserved structure of cofactor-binding motif, and results indicated that introducing the mutation K11A or R13A in CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the nucleotide-cofactor affinity of DHDPR. Lastly, the effects of these mutated DHDPRs on l-lysine production were investigated. The highest increase (26.2%) in l-lysine production was observed for JL-6 ΔdapB::Ec-dapB C115G,G116C , followed by JL-6 Cg-dapB C37G,G38C (21.4%) and JL-6 ΔdapB::Ec-dapB C46G,G47C (15.2%). This is the first report of a rational modification of DHDPR that enhances the l-lysine production and yield through the modulation of nucleotide-cofactor specificity. © 2018 Wiley Periodicals, Inc.

  10. Polynucleotide Phosphorylase, RNase E/G, and YbeY Are Involved in the Maturation of 4.5S RNA in Corynebacterium glutamicum.

    Science.gov (United States)

    Maeda, Tomoya; Tanaka, Yuya; Wachi, Masaaki; Inui, Masayuki

    2017-03-01

    Corynebacterium glutamicum has been applied for the industrial production of various metabolites, such as amino acids. To understand the biosynthesis of the membrane protein in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP is found in all three domains of life and plays an important role in the membrane insertion of proteins. SRP RNA is initially transcribed as precursor molecules; however, relatively little is known about its maturation. In C. glutamicum , SRP consists of the Ffh protein and 4.5S RNA lacking an Alu domain. In this study, we found that 3'-to-5' exoribonuclease, polynucleotide phosphorylase (PNPase), and two endo-type RNases, RNase E/G and YbeY, are involved in the 3' maturation of 4.5S RNA in C. glutamicum The mature form of 4.5S RNA was inefficiently formed in Δ rneG Δ pnp mutant cells, suggesting the existence of an alternative pathway for the 3' maturation of 4.5S RNA. Primer extension analysis also revealed that the 5' mature end of 4.5S RNA corresponds to that of the transcriptional start site. Immunoprecipitated Ffh protein contained immature 4.5S RNA in Δ pnp , Δ rneG , and Δ ybeY mutants, suggesting that 4.5S RNA precursors can interact with Ffh. These results imply that the maturation of 4.5S RNA can be performed in the 4.5S RNA-Ffh complex. IMPORTANCE Overproduction of a membrane protein, such as a transporter, is useful for engineering of strains of Corynebacterium glutamicum , which is a workhorse of amino acid production. To understand membrane protein biogenesis in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP contains the Ffh protein and SRP RNA and plays an important role in the membrane insertion of proteins. Although SRP RNA is highly conserved among the three domains of life, relatively little is known about its maturation. We show that PNPase, RNase E/G, and YbeY are involved in the 3' maturation of the SRP RNA (4.5S RNA) in

  11. Random mutagenesis in Corynebacterium glutamicum ATCC 13032 using an IS6100-based transposon vector identified the last unknown gene in the histidine biosynthesis pathway

    Directory of Open Access Journals (Sweden)

    Gaigalat Lars

    2006-08-01

    Full Text Available Abstract Background Corynebacterium glutamicum, a Gram-positive bacterium of the class Actinobacteria, is an industrially relevant producer of amino acids. Several methods for the targeted genetic manipulation of this organism and rational strain improvement have been developed. An efficient transposon mutagenesis system for the completely sequenced type strain ATCC 13032 would significantly advance functional genome analysis in this bacterium. Results A comprehensive transposon mutant library comprising 10,080 independent clones was constructed by electrotransformation of the restriction-deficient derivative of strain ATCC 13032, C. glutamicum RES167, with an IS6100-containing non-replicative plasmid. Transposon mutants had stable cointegrates between the transposon vector and the chromosome. Altogether 172 transposon integration sites have been determined by sequencing of the chromosomal inserts, revealing that each integration occurred at a different locus. Statistical target site analyses revealed an apparent absence of a target site preference. From the library, auxotrophic mutants were obtained with a frequency of 2.9%. By auxanography analyses nearly two thirds of the auxotrophs were further characterized, including mutants with single, double and alternative nutritional requirements. In most cases the nutritional requirement observed could be correlated to the annotation of the mutated gene involved in the biosynthesis of an amino acid, a nucleotide or a vitamin. One notable exception was a clone mutagenized by transposition into the gene cg0910, which exhibited an auxotrophy for histidine. The protein sequence deduced from cg0910 showed high sequence similarities to inositol-1(or 4-monophosphatases (EC 3.1.3.25. Subsequent genetic deletion of cg0910 delivered the same histidine-auxotrophic phenotype. Genetic complementation of the mutants as well as supplementation by histidinol suggests that cg0910 encodes the hitherto unknown

  12. Double mutation of cell wall proteins CspB and PBP1a increases secretion of the antibody Fab fragment from Corynebacterium glutamicum

    Science.gov (United States)

    2014-01-01

    Background Among other advantages, recombinant antibody-binding fragments (Fabs) hold great clinical and commercial potential, owing to their efficient tissue penetration compared to that of full-length IgGs. Although production of recombinant Fab using microbial expression systems has been reported, yields of active Fab have not been satisfactory. We recently developed the Corynebacterium glutamicum protein expression system (CORYNEX®) and demonstrated improved yield and purity for some applications, although the system has not been applied to Fab production. Results The Fab fragment of human anti-HER2 was successfully secreted by the CORYNEX® system using the conventional C. glutamicum strain YDK010, but the productivity was very low. To improve the secretion efficiency, we investigated the effects of deleting cell wall-related genes. Fab secretion was increased 5.2 times by deletion of pbp1a, encoding one of the penicillin-binding proteins (PBP1a), mediating cell wall peptidoglycan (PG) synthesis. However, this Δpbp1a mutation did not improve Fab secretion in the wild-type ATCC13869 strain. Because YDK010 carries a mutation in the cspB gene encoding a surface (S)-layer protein, we evaluated the effect of ΔcspB mutation on Fab secretion from ATCC13869. The Δpbp1a mutation showed a positive effect on Fab secretion only in combination with the ΔcspB mutation. The ΔcspBΔpbp1a double mutant showed much greater sensitivity to lysozyme than either single mutant or the wild-type strain, suggesting that these mutations reduced cell wall resistance to protein secretion. Conclusion There are at least two crucial permeability barriers to Fab secretion in the cell surface structure of C. glutamicum, the PG layer, and the S-layer. The ΔcspBΔpbp1a double mutant allows efficient Fab production using the CORYNEX® system. PMID:24731213

  13. Functional architecture and global properties of the Corynebacterium glutamicum regulatory network: Novel insights from a dataset with a high genomic coverage.

    Science.gov (United States)

    Freyre-González, Julio A; Tauch, Andreas

    2017-09-10

    Corynebacterium glutamicum is a Gram-positive, anaerobic, rod-shaped soil bacterium able to grow on a diversity of carbon sources like sugars and organic acids. It is a biotechnological relevant organism because of its highly efficient ability to biosynthesize amino acids, such as l-glutamic acid and l-lysine. Here, we reconstructed the most complete C. glutamicum regulatory network to date and comprehensively analyzed its global organizational properties, systems-level features and functional architecture. Our analyses show the tremendous power of Abasy Atlas to study the functional organization of regulatory networks. We created two models of the C. glutamicum regulatory network: all-evidences (containing both weak and strong supported interactions, genomic coverage=73%) and strongly-supported (only accounting for strongly supported evidences, genomic coverage=71%). Using state-of-the-art methodologies, we prove that power-law behaviors truly govern the connectivity and clustering coefficient distributions. We found a non-previously reported circuit motif that we named complex feed-forward motif. We highlighted the importance of feedback loops for the functional architecture, beyond whether they are statistically over-represented or not in the network. We show that the previously reported top-down approach is inadequate to infer the hierarchy governing a regulatory network because feedback bridges different hierarchical layers, and the top-down approach disregards the presence of intermodular genes shaping the integration layer. Our findings all together further support a diamond-shaped, three-layered hierarchy exhibiting some feedback between processing and coordination layers, which is shaped by four classes of systems-level elements: global regulators, locally autonomous modules, basal machinery and intermodular genes. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Efficient production of α-ketoglutarate in the gdh deleted Corynebacterium glutamicum by novel double-phase pH and biotin control strategy.

    Science.gov (United States)

    Li, Yanjun; Sun, Lanchao; Feng, Jia; Wu, Ruifang; Xu, Qingyang; Zhang, Chenglin; Chen, Ning; Xie, Xixian

    2016-06-01

    Production of L-glutamate using a biotin-deficient strain of Corynebacterium glutamicum has a long history. The process is achieved by controlling biotin at suboptimal dose in the initial fermentation medium, meanwhile feeding NH4OH to adjust pH so that α-ketoglutarate (α-KG) can be converted to L-glutamate. In this study, we deleted glutamate dehydrogenase (gdh1 and gdh2) of C. glutamicum GKG-047, an L-glutamate overproducing strain, to produce α-KG that is the direct precursor of L-glutamate. Based on the method of L-glutamate fermentation, we developed a novel double-phase pH and biotin control strategy for α-KG production. Specifically, NH4OH was added to adjust the pH at the bacterial growth stage and NaOH was used when the cells began to produce acid; besides adding an appropriate amount of biotin in the initial medium, certain amount of additional biotin was supplemented at the middle stage of fermentation to maintain a high cell viability and promote the carbon fixation to the flux of α-KG production. Under this control strategy, 45.6 g/L α-KG accumulated after 30-h fermentation in a 7.5-L fermentor and the productivity and yield achieved were 1.52 g/L/h and 0.42 g/g, respectively.

  15. Optimization of the IPP precursor supply for the production of lycopene, decaprenoxanthin and astaxanthin by Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Sabine A.E. Heider

    2014-08-01

    Full Text Available The biotechnologically relevant bacterium C. glutamicum, currently used for the million ton-scale production of amino acids for the food and feed industries, is pigmented due to synthesis of the rare cyclic C50 carotenoid decaprenoxanthin and its glucosides. The precursors of carotenoid biosynthesis, isopenthenyl pyrophosphate (IPP and its isomer dimethylallyl pyrophosphate (DMAPP, are synthesized in this organism via the methylerythritol phosphate (MEP or non-mevalonate pathway. Terminal pathway engineering in recombinant C. glutamicum permitted the production of various nonnative C50 and C40 carotenoids. Here, the role of engineering isoprenoid precursor supply for lycopene production by C. glutamicum was characterized. Overexpression of dxs encoding the enzyme that catalyzes the first committed step of the MEP-pathway by chromosomal promoter exchange in a prophage-cured, genome-reduced C. glutamicum strain improved lycopene formation. Similarly, an increased IPP supply was achieved by chromosomal integration of two artificial operons comprising MEP pathway genes under the control of a constitutive promoter. Combined overexpression of dxs and the other six MEP pathways genes in C. glutamicum strain LYC3-MEP was not synergistic with respect to improving lycopene accumulation. Based on C. glutamicum strain LYC3-MEP astaxanthin could be produced in the mg per g cell dry weight range when the endogenous genes crtE, crtB and crtI for conversion of geranylgeranyl pyrophosphate to lycopene were coexpressed with the genes for lycopene cyclase and β-carotene hydroxylase from Pantoea ananatis and carotene C(4 oxygenase from Brevundimonas aurantiaca.

  16. Enhancement of γ-aminobutyric acid production in recombinant Corynebacterium glutamicum by co-expressing two glutamate decarboxylase genes from Lactobacillus brevis.

    Science.gov (United States)

    Shi, Feng; Jiang, Junjun; Li, Yongfu; Li, Youxin; Xie, Yilong

    2013-11-01

    γ-Aminobutyric acid (GABA), a non-protein amino acid, is a bioactive component in the food, feed and pharmaceutical fields. To establish an effective single-step production system for GABA, a recombinant Corynebacterium glutamicum strain co-expressing two glutamate decarboxylase (GAD) genes (gadB1 and gadB2) derived from Lactobacillus brevis Lb85 was constructed. Compared with the GABA production of the gadB1 or gadB2 single-expressing strains, GABA production by the gadB1-gadB2 co-expressing strain increased more than twofold. By optimising urea supplementation, the total production of L-glutamate and GABA increased from 22.57 ± 1.24 to 30.18 ± 1.33 g L⁻¹, and GABA production increased from 4.02 ± 0.95 to 18.66 ± 2.11 g L⁻¹ after 84-h cultivation. Under optimal urea supplementation, L-glutamate continued to be consumed, GABA continued to accumulate after 36 h of fermentation, and the pH level fluctuated. GABA production increased to a maximum level of 27.13 ± 0.54 g L⁻¹ after 120-h flask cultivation and 26.32 g L⁻¹ after 60-h fed-batch fermentation. The conversion ratio of L-glutamate to GABA reached 0.60-0.74 mol mol⁻¹. By co-expressing gadB1 and gadB2 and optimising the urea addition method, C. glutamicum was genetically improved for de novo biosynthesis of GABA from its own accumulated L-glutamate.

  17. Sequence-based identification of inositol monophosphatase-like histidinol-phosphate phosphatases (HisN) in Corynebacterium glutamicum, Actinobacteria, and beyond.

    Science.gov (United States)

    Kulis-Horn, Robert Kasimir; Rückert, Christian; Kalinowski, Jörn; Persicke, Marcus

    2017-07-18

    The eighth step of L-histidine biosynthesis is carried out by an enzyme called histidinol-phosphate phosphatase (HolPase). Three unrelated HolPase families are known so far. Two of them are well studied: HAD-type HolPases known from Gammaproteobacteria like Escherichia coli or Salmonella enterica and PHP-type HolPases known from yeast and Firmicutes like Bacillus subtilis. However, the third family of HolPases, the inositol monophosphatase (IMPase)-like HolPases, present in Actinobacteria like Corynebacterium glutamicum (HisN) and plants, are poorly characterized. Moreover, there exist several IMPase-like proteins in bacteria (e.g. CysQ, ImpA, and SuhB) which are very similar to HisN but most likely do not participate in L-histidine biosynthesis. Deletion of hisN, the gene encoding the IMPase-like HolPase in C. glutamicum, does not result in complete L-histidine auxotrophy. Out of four hisN homologs present in the genome of C. glutamicum (impA, suhB, cysQ, and cg0911), only cg0911 encodes an enzyme with HolPase activity. The enzymatic properties of HisN and Cg0911 were determined, delivering the first available kinetic data for IMPase-like HolPases. Additionally, we analyzed the amino acid sequences of potential HisN, ImpA, SuhB, CysQ and Cg0911 orthologs from bacteria and identified six conserved sequence motifs for each group of orthologs. Mutational studies confirmed the importance of a highly conserved aspartate residue accompanied by several aromatic amino acid residues present in motif 5 for HolPase activity. Several bacterial proteins containing all identified HolPase motifs, but showing only moderate sequence similarity to HisN from C. glutamicum, were experimentally confirmed as IMPase-like HolPases, demonstrating the value of the identified motifs. Based on the confirmed IMPase-like HolPases two profile Hidden Markov Models (HMMs) were build using an iterative approach. These HMMs allow the fast, reliable detection and differentiation of the two

  18. The MurC ligase essential for peptidoglycan biosynthesis is regulated by the serine/threonine protein kinase PknA in Corynebacterium glutamicum.

    Science.gov (United States)

    Fiuza, Maria; Canova, Marc J; Patin, Delphine; Letek, Michal; Zanella-Cléon, Isabelle; Becchi, Michel; Mateos, Luís M; Mengin-Lecreulx, Dominique; Molle, Virginie; Gil, José A

    2008-12-26

    The Mur ligases play an essential role in the biosynthesis of bacterial cell-wall peptidoglycan and thus represent attractive targets for the design of novel antibacterials. These enzymes catalyze the stepwise formation of the peptide moiety of the peptidoglycan disaccharide peptide monomer unit. MurC is responsible of the addition of the first residue (L-alanine) onto the nucleotide precursor UDP-MurNAc. Phosphorylation of proteins by Ser/Thr protein kinases has recently emerged as a major physiological mechanism of regulation in prokaryotes. Herein, the hypothesis of a phosphorylation-dependent mechanism of regulation of the MurC activity was investigated in Corynebacterium glutamicum. We showed that MurC was phosphorylated in vitro by the PknA protein kinase. An analysis of the phosphoamino acid content indicated that phosphorylation exclusively occurred on threonine residues. Six phosphoacceptor residues were identified by mass spectrometry analysis, and we confirmed that mutagenesis to alanine residues totally abolished PknA-dependent phosphorylation of MurC. In vitro and in vivo ligase activity assays showed that the catalytic activity of MurC was impaired following mutation of these threonine residues. Further in vitro assays revealed that the activity of the MurC-phosphorylated isoform was severely decreased compared with the non-phosphorylated protein. To our knowledge, this is the first demonstration of a MurC ligase phosphorylation in vitro. The finding that phosphorylation is correlated with a decrease in MurC enzymatic activity could have significant consequences in the regulation of peptidoglycan biosynthesis.

  19. The MurC Ligase Essential for Peptidoglycan Biosynthesis Is Regulated by the Serine/Threonine Protein Kinase PknA in Corynebacterium glutamicum*

    Science.gov (United States)

    Fiuza, Maria; Canova, Marc J.; Patin, Delphine; Letek, Michal; Zanella-Cléon, Isabelle; Becchi, Michel; Mateos, Luís M.; Mengin-Lecreulx, Dominique; Molle, Virginie; Gil, José A.

    2008-01-01

    The Mur ligases play an essential role in the biosynthesis of bacterial cell-wall peptidoglycan and thus represent attractive targets for the design of novel antibacterials. These enzymes catalyze the stepwise formation of the peptide moiety of the peptidoglycan disaccharide peptide monomer unit. MurC is responsible of the addition of the first residue (l-alanine) onto the nucleotide precursor UDP-MurNAc. Phosphorylation of proteins by Ser/Thr protein kinases has recently emerged as a major physiological mechanism of regulation in prokaryotes. Herein, the hypothesis of a phosphorylation-dependent mechanism of regulation of the MurC activity was investigated in Corynebacterium glutamicum. We showed that MurC was phosphorylated in vitro by the PknA protein kinase. An analysis of the phosphoamino acid content indicated that phosphorylation exclusively occurred on threonine residues. Six phosphoacceptor residues were identified by mass spectrometry analysis, and we confirmed that mutagenesis to alanine residues totally abolished PknA-dependent phosphorylation of MurC. In vitro and in vivo ligase activity assays showed that the catalytic activity of MurC was impaired following mutation of these threonine residues. Further in vitro assays revealed that the activity of the MurC-phosphorylated isoform was severely decreased compared with the non-phosphorylated protein. To our knowledge, this is the first demonstration of a MurC ligase phosphorylation in vitro. The finding that phosphorylation is correlated with a decrease in MurC enzymatic activity could have significant consequences in the regulation of peptidoglycan biosynthesis. PMID:18974047

  20. Increased Production of Food-Grade d-Tagatose from d-Galactose by Permeabilized and Immobilized Cells of Corynebacterium glutamicum, a GRAS Host, Expressing d-Galactose Isomerase from Geobacillus thermodenitrificans.

    Science.gov (United States)

    Shin, Kyung-Chul; Sim, Dong-Hyun; Seo, Min-Ju; Oh, Deok-Kun

    2016-11-02

    The generally recognized as safe microorganism Corynebacterium glutamicum expressing Geobacillus thermodenitrificans d-galactose isomerase (d-GaI) was an efficient host for the production of d-tagatose, a functional sweetener. The d-tagatose production at 500 g/L d-galactose by the host was 1.4-fold higher than that by Escherichia coli expressing d-GaI. The d-tagatose-producing activity of permeabilized C. glutamicum (PCG) cells treated with 1% (w/v) Triton X-100 was 2.1-fold higher than that of untreated cells. Permeabilized and immobilized C. glutamicum (PICG) cells in 3% (w/v) alginate showed a 3.1-fold longer half-life at 50 °C and 3.1-fold higher total d-tagatose concentration in repeated batch reactions than PCG cells. PICG cells, which produced 165 g/L d-tagatose after 3 h, with a conversion of 55% (w/w) and a productivity of 55 g/L/h, showed significantly higher d-tagatose productivity than that reported for other cells. Thus, d-tagatose production by PICG cells may be an economical process to produce food-grade d-tagatose.

  1. Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum.

    Science.gov (United States)

    Busche, Tobias; Silar, Radoslav; Pičmanová, Martina; Pátek, Miroslav; Kalinowski, Jörn

    2012-09-03

    The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress response after the cells have

  2. Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Busche Tobias

    2012-09-01

    Full Text Available Abstract Background The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Results Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. Conclusions The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly

  3. Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum.

    Science.gov (United States)

    Brunger, Axel T; Das, Debanu; Deacon, Ashley M; Grant, Joanna; Terwilliger, Thomas C; Read, Randy J; Adams, Paul D; Levitt, Michael; Schröder, Gunnar F

    2012-04-01

    Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence.

  4. Corynebacterium glutamicum MTCC 2745 immobilized on granular activated carbon/MnFe2O4 composite: A novel biosorbent for removal of As(III) and As(V) ions.

    Science.gov (United States)

    Podder, M S; Majumder, C B

    2016-11-05

    The optimization of biosorption/bioaccumulation process of both As(III) and As(V) has been investigated by using the biosorbent; biofilm of Corynebacterium glutamicum MTCC 2745 supported on granular activated carbon/MnFe2O4 composite (MGAC). The presence of functional groups on the cell wall surface of the biomass that may interact with the metal ions was proved by FT-IR. To determine the most appropriate correlation for the equilibrium curves employing the procedure of the non-linear regression for curve fitting analysis, isotherm studies were performed for As(III) and As(V) using 30 isotherm models. The pattern of biosorption/bioaccumulation fitted well with Vieth-Sladek isotherm model for As(III) and Brouers-Sotolongo and Fritz-Schlunder-V isotherm models for As(V). The maximum biosorption/bioaccumulation capacity estimated using Langmuir model were 2584.668mg/g for As(III) and 2651.675mg/g for As(V) at 30°C temperature and 220min contact time. The results showed that As(III) and As(V) removal was strongly pH-dependent with an optimum pH value of 7.0. D-R isotherm studies specified that ion exchange might play a prominent role. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Wang, Zhihao; Chan, Siu Hung Joshua; Sudarsan, Suresh

    2016-01-01

    is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon. Initially, we found that a strain where the dedicated fructose...... uptake system had been inactivated (KO-ptsF) was hampered in growth on sucrose minimal medium, and suppressor mutants appeared readily. Comparative genomic analysis in conjunction with enzymatic assays revealed that suppression was linked to inactivation of the pfkB gene, encoding a fructose-1-phosphate...... kinase. Detailed characterization of KO-ptsF, KO-pfkB and double knock-out (DKO) derivatives revealed a strong role for sugar-phosphates, especially fructose-1-phosphate (F1P), in governing sugar as well as redox metabolism due to effects on transcriptional regulation of key genes. These findings allowed...

  6. Corynebacterium glutamicum promoters: a practical approach

    Czech Academy of Sciences Publication Activity Database

    Pátek, Miroslav; Holátko, Jiří; Busche, T.; Kalinowski, J.; Nešvera, Jan

    2013-01-01

    Roč. 6, č. 2 (2013), s. 103-117 ISSN 1751-7907 R&D Projects: GA ČR GPP302/12/P633 Institutional support: RVO:61388971 Key words : VITRO TRANSCRIPTION SYSTEM * L-LYSINE PRODUCTION * SIGMA -FACTOR SIGB Subject RIV: EE - Microbiology, Virology Impact factor: 3.023, year: 2013

  7. Modeling metabolic networks in C. glutamicum: a comparison of rate laws in combination with various parameter optimization strategies

    Directory of Open Access Journals (Sweden)

    Oldiges Marco

    2009-01-01

    Full Text Available Abstract Background To understand the dynamic behavior of cellular systems, mathematical modeling is often necessary and comprises three steps: (1 experimental measurement of participating molecules, (2 assignment of rate laws to each reaction, and (3 parameter calibration with respect to the measurements. In each of these steps the modeler is confronted with a plethora of alternative approaches, e. g., the selection of approximative rate laws in step two as specific equations are often unknown, or the choice of an estimation procedure with its specific settings in step three. This overall process with its numerous choices and the mutual influence between them makes it hard to single out the best modeling approach for a given problem. Results We investigate the modeling process using multiple kinetic equations together with various parameter optimization methods for a well-characterized example network, the biosynthesis of valine and leucine in C. glutamicum. For this purpose, we derive seven dynamic models based on generalized mass action, Michaelis-Menten and convenience kinetics as well as the stochastic Langevin equation. In addition, we introduce two modeling approaches for feedback inhibition to the mass action kinetics. The parameters of each model are estimated using eight optimization strategies. To determine the most promising modeling approaches together with the best optimization algorithms, we carry out a two-step benchmark: (1 coarse-grained comparison of the algorithms on all models and (2 fine-grained tuning of the best optimization algorithms and models. To analyze the space of the best parameters found for each model, we apply clustering, variance, and correlation analysis. Conclusion A mixed model based on the convenience rate law and the Michaelis-Menten equation, in which all reactions are assumed to be reversible, is the most suitable deterministic modeling approach followed by a reversible generalized mass action kinetics

  8. A novel genetic tool for metabolic optimization of Corynebacterium glutamicum: efficient and repetitive chromosomal integration of synthetic promoter-driven expression libraries

    DEFF Research Database (Denmark)

    Shen, Jing; Chen, Jun; Jensen, Peter Ruhdal

    2017-01-01

    readily could integrate into the attB site in this strain providing expression of the corresponding integrase. Subsequent expression of the Cre recombinase promoted recombination between the modified loxP sites, resulting in a strain only retaining the target insertions and an attB site. To simplify...... the procedure, non-replicating circular expression units for the phage integrase and the Cre recombinase were used. As a showcase, we used the tool to construct a battery of strains simultaneously expressing the two reporter genes, lacZ (encoding β-galactosidase) and gusA (encoding β...

  9. Advanced biotechnology: metabolically engineered cells for the bio-based production of chemicals and fuels, materials, and health-care products.

    Science.gov (United States)

    Becker, Judith; Wittmann, Christoph

    2015-03-09

    Corynebacterium glutamicum, Escherichia coli, and Saccharomyces cerevisiae in particular, have become established as important industrial workhorses in biotechnology. Recent years have seen tremendous progress in their advance into tailor-made producers, driven by the upcoming demand for sustainable processes and renewable raw materials. Here, the diversity and complexity of nature is simultaneously a challenge and a benefit. Harnessing biodiversity in the right manner through synergistic progress in systems metabolic engineering and chemical synthesis promises a future innovative bio-economy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. PcaO Positively Regulates pcaHG of the β-Ketoadipate Pathway in Corynebacterium glutamicum▿

    OpenAIRE

    Zhao, Ke-Xin; Huang, Yan; Chen, Xi; Wang, Nan-Xi; Liu, Shuang-Jiang

    2010-01-01

    We identified a new regulator, PcaO, which is involved in regulation of the protocatechuate (PCA) branch of the β-ketoadipate pathway in Corynebacterium glutamicum. PcaO is an atypical large ATP-binding LuxR family (LAL)-type regulator and does not have a Walker A motif. A mutant of C. glutamicum in which pcaO was disrupted (RES167ΔpcaO) was unable to grow on PCA, and growth on PCA was restored by complementation with pcaO. Both an enzymatic assay of PCA 3,4-dioxygenase activity (encoded by p...

  11. Production of amino acids - Genetic and metabolic engineering approaches.

    Science.gov (United States)

    Lee, Jin-Ho; Wendisch, Volker F

    2017-12-01

    The biotechnological production of amino acids occurs at the million-ton scale and annually about 6milliontons of l-glutamate and l-lysine are produced by Escherichia coli and Corynebacterium glutamicum strains. l-glutamate and l-lysine production from starch hydrolysates and molasses is very efficient and access to alternative carbon sources and new products has been enabled by metabolic engineering. This review focusses on genetic and metabolic engineering of amino acid producing strains. In particular, rational approaches involving modulation of transcriptional regulators, regulons, and attenuators will be discussed. To address current limitations of metabolic engineering, this article gives insights on recent systems metabolic engineering approaches based on functional tools and method such as genome reduction, amino acid sensors based on transcriptional regulators and riboswitches, CRISPR interference, small regulatory RNAs, DNA scaffolding, and optogenetic control, and discusses future prospects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The transcriptional regulatory network of Corynebacterium jeikeium K411 and its interaction with metabolic routes contributing to human body odor formation.

    Science.gov (United States)

    Barzantny, Helena; Schröder, Jasmin; Strotmeier, Jasmin; Fredrich, Eugenie; Brune, Iris; Tauch, Andreas

    2012-06-15

    Lipophilic corynebacteria are involved in the generation of volatile odorous products in the process of human body odor formation by degrading skin lipids and specific odor precursors. Therefore, these bacteria represent appropriate model systems for the cosmetic industry to examine axillary malodor formation on the molecular level. To understand the transcriptional control of metabolic pathways involved in this process, the transcriptional regulatory network of the lipophilic axilla isolate Corynebacterium jeikeium K411 was reconstructed from the complete genome sequence. This bioinformatic approach detected a gene-regulatory repertoire of 83 candidate proteins, including 56 DNA-binding transcriptional regulators, nine two-component systems, nine sigma factors, and nine regulators with diverse physiological functions. Furthermore, a cross-genome comparison among selected corynebacterial species of the taxonomic cluster 3 revealed a common gene-regulatory repertoire of 44 transcriptional regulators, including the MarR-like regulator Jk0257, which is exclusively encoded in the genomes of this taxonomical subline. The current network reconstruction comprises 48 transcriptional regulators and 674 gene-regulatory interactions that were assigned to five interconnected functional modules. Most genes involved in lipid degradation are under the combined control of the global cAMP-sensing transcriptional regulator GlxR and the LuxR-family regulator RamA, probably reflecting the essential role of lipid degradation in C. jeikeium. This study provides the first genome-scale in silico analysis of the transcriptional regulation of metabolism in a lipophilic bacterium involved in the formation of human body odor. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. SIALIDASE (NEURAMINIDASE) OF CORYNEBACTERIUM DIPHTHERIAE.

    Science.gov (United States)

    WARREN, L; SPEARING, C W

    1963-11-01

    Warren, Leonard (National Institute of Arthritis and Metabolic Diseases, Bethesda, Md.) and C. W. Spearing. Sialidase (neuraminidase) of Corynebacterium diphtheriae. J. Bacteriol. 86:950-955. 1963.-The characteristics of a sialidase produced by Corynebacterium diphtheriae were studied. The enzyme was partially purified from preparations of diphtheria toxin on a column of Sephadex G-75. By this means the lethal factor of diphtheria toxin was separated, in part, from the sialidase activity. There appeared to be a close immunological relationship between the sialidases of C. diphtheriae and clostridia, since a preparation of diphtheria antitoxin was as effective an inhibitor of diphtheria sialidase as of the sialidase of three species of clostridia. Conversely, antitoxin to clostridia inhibited diphtheria sialidase. Diphtheria antitoxin was essentially inactive toward influenza virus sialidase, and was completely inactive against purified sialidase of Vibrio cholerae. Removal of sialic acid from the proteins in a preparation of diphtheria antitoxin did not alter the inhibitory activity of the antitoxin against diphtheria sialidase. The enzyme operated optimally at pH 5.5 and did not require calcium ions for activity. The substrate specificity of diphtheria sialidase appears to be the same as that of other previously described sialidases.

  14. Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient

    Science.gov (United States)

    2012-01-01

    Background Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. Results The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W) gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. Conclusions The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of this newly recognized

  15. Genealogy profiling through strain improvement by using metabolic network analysis: metabolic flux genealogy of several generations of lysine-producing corynebacteria.

    Science.gov (United States)

    Wittmann, Christoph; Heinzle, Elmar

    2002-12-01

    A comprehensive approach of metabolite balancing, (13)C tracer studies, gas chromatography-mass spectrometry, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and isotopomer modeling was applied for comparative metabolic network analysis of a genealogy of five successive generations of lysine-producing Corynebacterium glutamicum. The five strains examined (C. glutamicum ATCC 13032, 13287, 21253, 21526, and 21543) were previously obtained by random mutagenesis and selection. Throughout the genealogy, the lysine yield in batch cultures increased markedly from 1.2 to 24.9% relative to the glucose uptake flux. Strain optimization was accompanied by significant changes in intracellular flux distributions. The relative pentose phosphate pathway (PPP) flux successively increased, clearly corresponding to the product yield. Moreover, the anaplerotic net flux increased almost twofold as a consequence of concerted regulation of C(3) carboxylation and C(4) decarboxylation fluxes to cover the increased demand for lysine formation; thus, the overall increase was a consequence of concerted regulation of C(3) carboxylation and C(4) decarboxylation fluxes. The relative flux through isocitrate dehydrogenase dropped from 82.7% in the wild type to 59.9% in the lysine-producing mutants. In contrast to the NADPH demand, which increased from 109 to 172% due to the increasing lysine yield, the overall NADPH supply remained constant between 185 and 196%, resulting in a decrease in the apparent NADPH excess through strain optimization. Extrapolated to industrial lysine producers, the NADPH supply might become a limiting factor. The relative contributions of PPP and the tricarboxylic acid cycle to NADPH generation changed markedly, indicating that C. glutamicum is able to maintain a constant supply of NADPH under completely different flux conditions. Statistical analysis by a Monte Carlo approach revealed high precision for the estimated fluxes, underlining the

  16. Corynebacterium ulcerans cutaneous diphtheria.

    Science.gov (United States)

    Moore, Luke S P; Leslie, Asuka; Meltzer, Margie; Sandison, Ann; Efstratiou, Androulla; Sriskandan, Shiranee

    2015-09-01

    We describe the case of a patient with cutaneous diphtheria caused by toxigenic Corynebacterium ulcerans who developed a right hand flexor sheath infection and symptoms of sepsis such as fever, tachycardia, and elevated C-reactive protein, after contact with domestic cats and dogs, and a fox. We summarise the epidemiology, clinical presentation, microbiology, diagnosis, therapy, and public health aspects of this disease, with emphasis on improving recognition. In many European countries, C ulcerans has become the organism commonly associated with cutaneous diphtheria, usually seen as an imported tropical disease or resulting from contact with domestic and agricultural animals. Diagnosis relies on bacterial culture and confirmation of toxin production, with management requiring appropriate antimicrobial therapy and prompt administration of antitoxin, if necessary. Early diagnosis is essential for implementation of control measures and clear guidelines are needed to assist clinicians in managing clinical diphtheria. This case was a catalyst to the redrafting of the 2014 national UK interim guidelines for the public health management of diphtheria, released as final guidelines in March, 2015. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Pathway Construction in Corynebacterium glutamicum and Strain Engineering To Produce Rare Sugars from Glycerol.

    Science.gov (United States)

    Yang, Jiangang; Zhu, Yueming; Men, Yan; Sun, Shangshang; Zeng, Yan; Zhang, Ying; Sun, Yuanxia; Ma, Yanhe

    2016-12-21

    Rare sugars are valuable natural products widely used in pharmaceutical and food industries. In this study, we expected to synthesize rare ketoses from abundant glycerol using dihydroxyacetone phosphate (DHAP)-dependent aldolases. First, a new glycerol assimilation pathway was constructed to synthesize DHAP. The enzymes which convert glycerol to 3-hydroxypropionaldehyde and l-glyceraldehyde were selected, and their corresponding aldehyde synthesis pathways were constructed in vivo. Four aldol pathways based on different aldolases and phosphorylase were gathered. Next, three pathways were assembled and the resulting strains synthesized 5-deoxypsicose, 5-deoxysorbose, and 5-deoxyfructose from glucose and glycerol and produce l-fructose, l-tagatose, l-sorbose, and l-psicose with glycerol as the only carbon source. To achieve higher product titer and yield, the recombinant strains were further engineered and fermentation conditions were optimized. Fed-batch culture of engineered strains obtained 38.1 g/L 5-deoxypsicose with a yield of 0.91 ± 0.04 mol product per mol of glycerol and synthesized 20.8 g/L l-fructose, 10.3 g/L l-tagatose, 1.2 g/L l-sorbose, and 0.95 g/L l-psicose.

  18. The small 6C RNA of Corynebacterium glutamicum is involved in the SOS response

    Czech Academy of Sciences Publication Activity Database

    Pahlke, J.; Dostálová, Hana; Holátko, Jiří; Degner, U.; Bott, M.; Pátek, Miroslav; Polen, T.

    2016-01-01

    Roč. 13, č. 9 (2016), s. 848-860 ISSN 1547-6286 Institutional support: RVO:61388971 Keywords : Actinobacteria * branched morphology * cell division Subject RIV: EE - Microbiology, Virology Impact factor: 3.900, year: 2016

  19. Corynebacterium species isolated from patients with mastitis.

    Science.gov (United States)

    Paviour, Sue; Musaad, Sahar; Roberts, Sally; Taylor, Graeme; Taylor, Susan; Shore, Keith; Lang, Selwyn; Holland, David

    2002-12-01

    Corynebacteria were isolated from breast tissue, pus, or deep wound swabs of 24 women; the most common species isolated was the newly described Corynebacterium kroppenstedtii, followed by Corynebacterium amycolatum and Corynebacterium tuberculostearicum. Gram-positive bacilli were seen in samples sent for culture or in histological specimens for 12 women, and 9 of the 12 women from whom adequate histological specimens were obtained had conditions that met the criteria for granulomatous lobular mastitis, a chronic inflammatory disease of unknown etiology.

  20. Corynebacterium propinquum associated with acute, nongonococcal urethritis.

    Science.gov (United States)

    Abdolrasouli, Alireza; Roushan, Azita

    2013-10-01

    Corynebacterium propinquum is usually considered part of the normal human oropharyngeal flora and is rarely responsible for clinical infection. We report here what seems to be the first case of acute purulent urethral discharge in a young Iranian man with urethritis acquired after orogenital contact. Attention should be devoted to less common nondiphtheriae Corynebacterium species for differential diagnosis.

  1. Cystic neutrophilic granulomatous mastitis associated with Corynebacterium including Corynebacterium kroppenstedtii.

    Science.gov (United States)

    Johnstone, Kate J; Robson, Jennifer; Cherian, Sarah G; Wan Sai Cheong, Jenny; Kerr, Kris; Bligh, Judith F

    2017-06-01

    Granulomatous (lobular) mastitis is a rare inflammatory breast disease affecting parous reproductive-aged women. Once considered idiopathic, there is growing evidence of an association with corynebacteria infection, especially in the setting of a distinct histological pattern termed cystic neutrophilic granulomatous mastitis (CNGM). We describe 15 cases with histological features either confirming (n = 12) or suggesting (n = 3) CNGM, and concurrent microbiological evidence of Corynebacterium species. The organism was detected by culture or 16S rRNA gene sequencing of specimens obtained at surgery or fine needle aspiration. In seven cases, Gram-positive organisms were seen within vacuolated spaces. Speciation was performed in nine cases, with Corynebacterium kroppenstedtii subsequently identified. These cases provide further evidence in support of this association and in doing so highlight the importance of recognising these histological clues as well as the limitations of Gram stain and microbiological culture in detecting this previously under-recognised disease process. Copyright © 2017 Royal College of Pathologists of Australasia. All rights reserved.

  2. Corynebacterium jeikeium jk0268 constitutes for the 40 amino acid long PorACj, which forms a homooligomeric and anion-selective cell wall channel.

    Directory of Open Access Journals (Sweden)

    Narges Abdali

    Full Text Available Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.

  3. Draft Genome Sequence of Corynebacterium kefirresidentii SB, Isolated from Kefir.

    Science.gov (United States)

    Blasche, Sonja; Kim, Yongkyu; Patil, Kiran R

    2017-09-14

    The genus Corynebacterium includes Gram-positive species with a high G+C content. We report here a novel species, Corynebacterium kefirresidentii SB, isolated from kefir grains collected in Germany. Its draft genome sequence was remarkably dissimilar (average nucleotide identity, 76.54%) to those of other Corynebacterium spp., confirming that this is a unique novel species. Copyright © 2017 Blasche et al.

  4. Corynebacterium macginleyi isolated from a corneal ulcer

    Directory of Open Access Journals (Sweden)

    Kathryn Ruoff

    2010-02-01

    Full Text Available We report the isolation of Corynebacterium macginleyi from the corneal ulcer culture of a patient, later enrolled in the Steroids for Corneal Ulcer Trial (SCUT. To our knowledge this is the first published report from North America of the recovery of C. macginleyi from a serious ocular infection.

  5. A Spontaneous Joint Infection with Corynebacterium striatum▿

    OpenAIRE

    Scholle, David

    2006-01-01

    Corynebacterium striatum is a ubiquitous saprophyte with the potential to cause bacteremia in immunocompromised patients. Until now, spontaneous infection of a natural joint has not been reported. When phenotyping failed, gene sequencing was used to identify the species. The isolate demonstrated high-level resistance to most antibiotics.

  6. Desulfurization of dibenzothiophene by Corynebacterium sp. strain SY1

    International Nuclear Information System (INIS)

    Omori, Toshio; Monna, L.; Saiki, Yuko; Kodama, Tohru

    1992-01-01

    Strain SY1, identified as a Corynebacterium sp., was isolated on the basis of the ability to utilize dibenzothiophene (DBT) as a sole source of sulfur. Strain SY1 could utilize a wide range of organic and inorganic sulfur compounds, such as DBT sulfone, dimethyl sulfide, dimethyl sulfoxide, dimethyl sulfone, CS 2 , FeS 2 , and even elemental sulfur. Strain SY1 metabolized DBT to dibenzothiophene-5-oxide, DBT sulfone, and 2-hydroxybiphenyl, which was subsequently nitrated to produce at least two different hydroxynitrobiphenyls during cultivation. These metabolites were separated by silica gel column chromatography and identified by nuclear magnetic resonance, UV, and mass spectral techniques. Resting cells of SY1 desulfurized toluenesulfonic acid and released sulfite anion. On the basis of these results, a new DBT degradation pathway is proposed

  7. Corynebacterium pilbarense sp. nov., a non-lipophilic corynebacterium isolated from a human ankle aspirate.

    Science.gov (United States)

    Aravena-Roman, M; Spröer, C; Sträubler, B; Inglis, T; Yassin, A F

    2010-07-01

    A non-lipophilic coryneform bacterium isolated from an anaerobic Bactec bottle inoculated with an ankle aspirate from a male patient was characterized by phenotypic and molecular taxonomic methods. Chemotaxonomic investigations revealed the presence of short-chain mycolic acids in the cell wall of the bacterium, a feature consistent with members of the genus Corynebacterium. Comparative 16S rRNA gene sequence analysis demonstrated that the isolate displayed 92.0-99.0 % gene sequence similarity with members of the genus Corynebacterium, with Corynebacterium ureicelerivorans as the most closely related phylogenetic species (99.0 % gene sequence similarity). However, the isolate could be genomically separated from C. ureicelerivorans on the basis of DNA-DNA hybridization studies (39.5 % relatedness). Furthermore, the isolate could also be differentiated from C. ureicelerivorans and other species of the genus Corynebacterium on the basis of biochemical properties. Based on both phenotypic and phylogenetic evidence, it is proposed that this isolate be classified as representing a novel species, Corynebacterium pilbarense sp. nov. (type strain IMMIB WACC 658(T)=DSM 45350(T)=CCUG 57942(T)).

  8. Increased expression of pyruvate carboxylase and biotin protein ligase increases lysine production in a biotin prototrophic Corynebacterium glutamicum strain

    DEFF Research Database (Denmark)

    Wang, Zhihao; Moslehi-Jenabian, Soloomeh; Solem, Christian

    2015-01-01

    , and achieved biotin prototrophy. We found that AHP-3, containing pBIO, was able to produce lysine in a medium lacking biotin and that the lysine yield on glucose was similar to what is obtained when using a medium containing biotin. However, there was a decrease in specific growth rate of 20% when the strain...... pimeloyl-Acyl Carrier Protein [ACP]) formation. Pyruvate carboxylase (pycA), a biotin-dependent enzyme needed for lysine biosynthesis and biotin ligase (birA), which is responsible for attaching biotin to pyruvate carboxylase, were overexpressed by replacing the native promoters with the strong superoxide...... dismutase (sod) promoter, to see whether growth could be restored. Neither pycA nor birA overexpression, whether alone or in combination, had an effect on specific growth rate, but they did have a positive effect on lysine yield, which increased by 55% in the strain overexpressing both enzymes....

  9. Use of In Vitro Transcription System for Analysis of Corynebacterium glutamicum Promoters Recognized by Two Sigma Factors

    Czech Academy of Sciences Publication Activity Database

    Šilar, Radoslav; Holátko, Jiří; Rucká, Lenka; Rapoport, Andrey; Dostálová, Hana; Kadeřábková, Pavla; Nešvera, Jan; Pátek, Miroslav

    2016-01-01

    Roč. 73, č. 3 (2016), s. 401-408 ISSN 0343-8651 Institutional support: RVO:61388971 Keywords : GENE-EXPRESSION * REGULATORY NETWORK * BACILLUS-SUBTILIS Subject RIV: EE - Microbiology , Virology Impact factor: 1.322, year: 2016

  10. FluxPyt: a Python-based free and open-source software for 13C-metabolic flux analyses.

    Science.gov (United States)

    Desai, Trunil S; Srivastava, Shireesh

    2018-01-01

    13 C-Metabolic flux analysis (MFA) is a powerful approach to estimate intracellular reaction rates which could be used in strain analysis and design. Processing and analysis of labeling data for calculation of fluxes and associated statistics is an essential part of MFA. However, various software currently available for data analysis employ proprietary platforms and thus limit accessibility. We developed FluxPyt, a Python-based truly open-source software package for conducting stationary 13 C-MFA data analysis. The software is based on the efficient elementary metabolite unit framework. The standard deviations in the calculated fluxes are estimated using the Monte-Carlo analysis. FluxPyt also automatically creates flux maps based on a template for visualization of the MFA results. The flux distributions calculated by FluxPyt for two separate models: a small tricarboxylic acid cycle model and a larger Corynebacterium glutamicum model, were found to be in good agreement with those calculated by a previously published software. FluxPyt was tested in Microsoft™ Windows 7 and 10, as well as in Linux Mint 18.2. The availability of a free and open 13 C-MFA software that works in various operating systems will enable more researchers to perform 13 C-MFA and to further modify and develop the package.

  11. ORF Sequence: NC_003450 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available lase [Corynebacterium glutamicum ATCC 13032] MTVRPIVIHGDPVLHNPTQLVTEDVSELQELIADMYETMDVANGVGLAANQIGVSKRIFVYDCPDDEGVMHKGCFINPVLETSEIPET...MPADDGSDEEGCLSVPGEGFPTGRAHWAKVTGLNEKGEEVSVEAEGFLARCFQHEVGHLDGFLYTDVLIGRWKRMAKKAIKANGWTEPGLTWMPGEDEDPFGHDA

  12. Isolamento de Corynebacterium aquaticum em leite bubalino

    Directory of Open Access Journals (Sweden)

    Andréa Alice da Fonseca Oliveira

    2005-08-01

    Full Text Available Estudou-se 548 quartos mamários de búfalas, realizando-se exame clínico, CMT para detecção de mastite e coleta de amostras para isolamento bacteriano. Houve crescimento em duas amostras de Corynebacterium aquaticum caracterizadas bioquimicamente. Relata-se a participação do agente como colonizador do úbere e possível causador de mastites em bubalinos.

  13. Identification and characterization of smallest pore-forming protein in the cell wall of pathogenic Corynebacterium urealyticum DSM 7109.

    Science.gov (United States)

    Abdali, Narges; Younas, Farhan; Mafakheri, Samaneh; Pothula, Karunakar R; Kleinekathöfer, Ulrich; Tauch, Andreas; Benz, Roland

    2018-05-09

    Corynebacterium urealyticum, a pathogenic, multidrug resistant member of the mycolata, is known as causative agent of urinary tract infections although it is a bacterium of the skin flora. This pathogenic bacterium shares with the mycolata the property of having an unusual cell envelope composition and architecture, typical for the genus Corynebacterium. The cell wall of members of the mycolata contains channel-forming proteins for the uptake of solutes. In this study, we provide novel information on the identification and characterization of a pore-forming protein in the cell wall of C. urealyticum DSM 7109. Detergent extracts of whole C. urealyticum cultures formed in lipid bilayer membranes slightly cation-selective pores with a single-channel conductance of 1.75 nS in 1 M KCl. Experiments with different salts and non-electrolytes suggested that the cell wall pore of C. urealyticum is wide and water-filled and has a diameter of about 1.8 nm. Molecular modelling and dynamics has been performed to obtain a model of the pore. For the search of the gene coding for the cell wall pore of C. urealyticum we looked in the known genome of C. urealyticum for a similar chromosomal localization of the porin gene to known porH and porA genes of other Corynebacterium strains. Three genes are located between the genes coding for GroEL2 and polyphosphate kinase (PKK2). Two of the genes (cur_1714 and cur_1715) were expressed in different constructs in C. glutamicum ΔporAΔporH and in porin-deficient BL21 DE3 Omp8 E. coli strains. The results suggested that the gene cur_1714 codes alone for the cell wall channel. The cell wall porin of C. urealyticum termed PorACur was purified to homogeneity using different biochemical methods and had an apparent molecular mass of about 4 kDa on tricine-containing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Biophysical characterization of the purified protein (PorACur) suggested indeed that cur_1714 is the gene

  14. Enhancement of L-Serine Production by Corynebacterium ...

    African Journals Online (AJOL)

    glutamicum SYPS-062 cultivation process for efficient production of L-serine on a large scale. ... central intermediate for a number of cellular .... impeller, oxygen and pH electrodes, under the ... equation. The yield of L-serine was regressed with respect to the medium ..... is not essential for activity but is required for inhibition.

  15. J-GLOBAL MeSH Dictionary: Corynebacterium pseudotuberculosis [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term Corynebacterium pseudotuberculosis... 名詞 一般 * * * * Corynebacterium pseudotuberculosis ... MeSH D016925 200906025325177003 C LS07 UNKNOWN_2 Corynebacterium pseudotuberculosis

  16. Staphylococcus aureus shifts towards commensalism in response to Corynebacterium species

    Directory of Open Access Journals (Sweden)

    Matthew M Ramsey

    2016-08-01

    Full Text Available Staphylococcus aureus–human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe-microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, S. aureus displayed diminished fitness in experimental in vivo coinfection with C. striatum when compared to monoinfection. These data support a model in which S. aureus shifts from virulence towards a commensal state when exposed to commensal Corynebacterium species.

  17. Improved L-ornithine production in Corynebacterium crenatum by introducing an artificial linear transacetylation pathway.

    Science.gov (United States)

    Shu, Qunfeng; Xu, Meijuan; Li, Jing; Yang, Taowei; Zhang, Xian; Xu, Zhenghong; Rao, Zhiming

    2018-05-04

    L-Ornithine is a non-protein amino acid with extensive applications in the food and pharmaceutical industries. In this study, we performed metabolic pathway engineering of an L-arginine hyper-producing strain of Corynebacterium crenatum for L-ornithine production. First, we amplified the L-ornithine biosynthetic pathway flux by blocking the competing branch of the pathway. To enhance L-ornithine synthesis, we performed site-directed mutagenesis of the ornithine-binding sites to solve the problem of L-ornithine feedback inhibition for ornithine acetyltransferase. Alternatively, the genes argA from Escherichia coli and argE from Serratia marcescens, encoding the enzymes N-acetyl glutamate synthase and N-acetyl-L-ornithine deacetylase, respectively, were introduced into Corynebacterium crenatum to mimic the linear pathway of L-ornithine biosynthesis. Fermentation of the resulting strain in a 5-L bioreactor allowed a dramatically increased production of L-ornithine, 40.4 g/L, with an overall productivity of 0.673 g/L/h over 60 h. This demonstrates that an increased level of transacetylation is beneficial for L-ornithine biosynthesis.

  18. Corynebacterium minutissimum vascular graft infection: case report and review of 281 cases of prosthetic device-related Corynebacterium infection.

    Science.gov (United States)

    Reece, Rebecca M; Cunha, Cheston B; Rich, Josiah D

    2014-09-01

    Corynebacterium spp. have proven their pathogenic potential in causing infections, particularly in the setting of immunosuppression and prosthetic devices. We conducted a PubMed literature review of all cases of Corynebacterium prosthetic device infections published in the English language through December 2013. The majority of cases involved peritoneal dialysis and central venous catheters, but prosthetic joints and central nervous system shunts/drains were also involved. The management of these cases in terms of retention or removal of the device was not uniform; however, the overall mortality remained the same among both groups. All of these prosthetic device infections pose potential problems in management when the device cannot be removed safely for the patient, especially with the lack of data on the pathogenicity of Corynebacterium species. However with better identification of species and sensitivities, successful treatment is possible even with retention of the device.

  19. Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii.

    Science.gov (United States)

    Hagemann, Jürgen Benjamin; Essig, Andreas; Herrmann, Manuel; Liebold, Andreas; Quader, Mohamed Abo

    2015-12-01

    Corynebacterium (C.) kroppenstedtii is a rarely detected agent of bacterial infections in humans. Here, we describe the first case of prosthetic valve endocarditis caused by C. kroppenstedtii. Application of molecular methods using surgically excised valve tissue was a cornerstone for the establishment of the microbiological diagnosis, which is crucial for targeted antimicrobial treatment. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Urethritis due to corynebacterium striatum: An emerging germ.

    Science.gov (United States)

    Frikh, Mohammed; El Yaagoubi, Imad; Lemnouer, Abdelhay; Elouennass, Mostafa

    2015-01-01

    Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is part of mucous and skin flora. It has been considered as a causative agent of many infections in intensive care, neurology, traumatology and urology, but was never implicated in non-gonococcal urethritis. We report the case of a nosocomial urethritis due to Corynebacterium striatum following resection of an intrameatus condyloma.

  1. Over-expression of NAD kinase in Corynebacterium crenatum and ...

    African Journals Online (AJOL)

    in Corynebacterium crenatum SYPA5-5 and to study its impact in presence of high (HOS) ... Results: In HOS condition, NAD+ kinase activity increased by 116 %, while ... (NADPH), an important co-enzyme during ... Polymerase, TaKaRa) using C. crenatum .... were washed with cold 100 mM PBS (pH 7.5) ..... Catalase and.

  2. Experimental transmission of Corynebacterium pseudotuberculosis in horses by house flies

    Science.gov (United States)

    The route of infection of pigeon fever remains undetermined. The purpose of this study was to investigate house flies (Musca domestica L.) as vectors of Corynebacterium pseudotuberculosis in horses. Eight ponies were used in a randomized, controlled, blinded experimental study. Ten wounds were creat...

  3. Native valve endocarditis due to Corynebacterium group JK.

    Science.gov (United States)

    Moffie, B G; Veenendaal, R A; Thompson, J

    1990-12-01

    We report a case of a 32-yr-old woman on chronic intermittent haemodialysis, who developed endocarditis due to a Corynebacterium group JK, involving both the native aortic and mitral valves. Despite a four-week treatment with vancomycin, an aortic root abscess developed. The diagnosis was confirmed on autopsy.

  4. Metabolic engineering of Escherichia coli for the production of riboflavin

    Science.gov (United States)

    2014-01-01

    Background Riboflavin (vitamin B2), the precursor of the flavin cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is used commercially as an animal feed supplement and food colorant. E. coli is a robust host for various genetic manipulations and has been employed for efficient production of biofuels, polymers, amino acids, and bulk chemicals. Thus, the aim of this study was to understand the metabolic capacity of E. coli for the riboflavin production by modification of central metabolism, riboflavin biosynthesis pathway and optimization of the fermentation conditions. Results The basic producer RF01S, in which the riboflavin biosynthesis genes ribABDEC from E. coli were overexpressed under the control of the inducible trc promoter, could accumulate 229.1 mg/L of riboflavin. Further engineering was performed by examining the impact of expression of zwf (encodes glucose 6-phosphate dehydrogenase) and gnd (encodes 6-phosphogluconate dehydrogenase) from Corynebacterium glutamicum and pgl (encodes 6-phosphogluconolactonase) from E. coli on riboflavin production. Deleting pgi (encodes glucose-6-phosphate isomerase) and genes of Entner-Doudoroff (ED) pathway successfully redirected the carbon flux into the oxidative pentose phosphate pathway, and overexpressing the acs (encodes acetyl-CoA synthetase) reduced the acetate accumulation. These modifications increased riboflavin production to 585.2 mg/L. By further modulating the expression of ribF (encodes riboflavin kinase) for reducing the conversion of riboflavin to FMN in RF05S, the final engineering strain RF05S-M40 could produce 1036.1 mg/L riboflavin in LB medium at 37°C. After optimizing the fermentation conditions, strain RF05S-M40 produced 2702.8 mg/L riboflavin in the optimized semi-defined medium, which was a value nearly 12-fold higher than that of RF01S, with a yield of 137.5 mg riboflavin/g glucose. Conclusions The engineered strain RF05S-M40 has the highest yield among all

  5. Metabolic engineering of Escherichia coli for the production of riboflavin.

    Science.gov (United States)

    Lin, Zhenquan; Xu, Zhibo; Li, Yifan; Wang, Zhiwen; Chen, Tao; Zhao, Xueming

    2014-07-16

    Riboflavin (vitamin B2), the precursor of the flavin cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is used commercially as an animal feed supplement and food colorant. E. coli is a robust host for various genetic manipulations and has been employed for efficient production of biofuels, polymers, amino acids, and bulk chemicals. Thus, the aim of this study was to understand the metabolic capacity of E. coli for the riboflavin production by modification of central metabolism, riboflavin biosynthesis pathway and optimization of the fermentation conditions. The basic producer RF01S, in which the riboflavin biosynthesis genes ribABDEC from E. coli were overexpressed under the control of the inducible trc promoter, could accumulate 229.1 mg/L of riboflavin. Further engineering was performed by examining the impact of expression of zwf (encodes glucose 6-phosphate dehydrogenase) and gnd (encodes 6-phosphogluconate dehydrogenase) from Corynebacterium glutamicum and pgl (encodes 6-phosphogluconolactonase) from E. coli on riboflavin production. Deleting pgi (encodes glucose-6-phosphate isomerase) and genes of Entner-Doudoroff (ED) pathway successfully redirected the carbon flux into the oxidative pentose phosphate pathway, and overexpressing the acs (encodes acetyl-CoA synthetase) reduced the acetate accumulation. These modifications increased riboflavin production to 585.2 mg/L. By further modulating the expression of ribF (encodes riboflavin kinase) for reducing the conversion of riboflavin to FMN in RF05S, the final engineering strain RF05S-M40 could produce 1036.1 mg/L riboflavin in LB medium at 37°C. After optimizing the fermentation conditions, strain RF05S-M40 produced 2702.8 mg/L riboflavin in the optimized semi-defined medium, which was a value nearly 12-fold higher than that of RF01S, with a yield of 137.5 mg riboflavin/g glucose. The engineered strain RF05S-M40 has the highest yield among all reported riboflavin production

  6. Application of granular activated carbon/MnFe2O4 composite immobilized on C. glutamicum MTCC 2745 to remove As(III) and As(V): Kinetic, mechanistic and thermodynamic studies

    Science.gov (United States)

    Podder, M. S.; Majumder, C. B.

    2016-01-01

    The main objective of the present study was to investigate the efficiency of Corynebacterium glutamicum MTCC 2745 immobilized on granular activated carbon/MnFe2O4 (GAC/MnFe2O4) composite to treat high concentration of arsenic bearing wastewater. Non-linear regression analysis was done for determining the best-fit kinetic model on the basis of three correlation coefficients and three error functions and also for predicting the parameters involved in kinetic models. The results showed that Fractal-like mixed 1,2 order model for As(III) and Brouser-Weron-Sototlongo as well as Fractal-like pseudo second order models for As(V) were proficient to provide realistic description of biosorption/bioaccumulation kinetic. Applicability of mechanistic models in the current study exhibited that the rate governing step in biosorption/bioaccumulation of both As(III) and As(V) was film diffusion rather than intraparticle diffusion. The evaluated thermodynamic parameters ΔG0, ΔH0 and ΔS0 revealed that biosorption/bioaccumulation of both As(III) and As(V) was feasible, spontaneous and exothermic under studied conditions.

  7. Corynebacterium tapiri sp. nov. and Corynebacterium nasicanis sp. nov., isolated from a tapir and a dog, respectively.

    Science.gov (United States)

    Baumgardt, Sandra; Loncaric, Igor; Kämpfer, Peter; Busse, Hans-Jürgen

    2015-11-01

    Two Gram-stain-positive bacterial isolates, strain 2385/12T and strain 2673/12T were isolated from a tapir and a dog's nose, respectively. The two strains were rod to coccoid-shaped, catalase-positive and oxidase-negative. The highest 16S rRNA gene sequence similarity identified Corynebacterium singulare CCUG 37330T (96.3% similarity) as the nearest relative of strain 2385/12T and suggested the isolate represented a novel species. Corynebacterium humireducens DSM 45392T (98.7% 16S rRNA gene sequence similarity) was identified as the nearest relative of strain 2673/12T. Results from DNA-DNA hybridization with the type strain of C. humireducens demonstrated that strain 2673/12T also represented a novel species. Strain 2385/12T showed a quinone system consisting predominantly of menaquinones MK-8(H2) and MK-9(H2) whereas strain 2673/12T contained only MK-8(H2) as predominant quinone. The polar lipid profiles of the two strains showed the major compounds phosphatidylglycerol, diphosphatidylglycerol and an unidentified glycolipid. Phosphatidylinositol was identified as another major lipid in 2673/12T whereas it was only found in moderate amounts in strain 2385/12T. Furthermore, moderate to minor amounts of phosphatidylinositol-mannoside, β-gentiobiosyl diacylglycerol and variable counts of several unidentified lipids were detected in the two strains. Both strains contained corynemycolic acids. The polyamine patterns were characterized by the major compound putrescine in strain 2385/12T and spermidine in strain 2673/12T. In the fatty acid profiles, predominantly C18:1ω9c and C16:0 were detected. The two strains are distinguishable from each other and the nearest related established species of the genus Corynebacterium phylogenetically and phenotypically. In conclusion, two novel species of the genus Corynebacterium are proposed, namely Corynebacterium tapiri sp. nov. (type strain, 2385/12T = CCUG 65456T = LMG 28165T) and Corynebacterium nasicanis sp. nov. (type

  8. Interdigital foot infections: Corynebacterium minutissimum and agents of superficial mycoses

    Directory of Open Access Journals (Sweden)

    Fatma Mutlu Sariguzel

    2014-09-01

    Full Text Available Interdigital foot infections are mostly caused initially by dermatophytes, yeasts and less frequently by bacteria. Erythrasma caused by Corynebacterium minutissimum can be confused with superficial mycoses. The aim of the study was to determine the prevalence of the etiologic agents of superficial mycoses and the frequency of Corynebacterium minutissimum in interdigital foot infections. All the samples obtained from the 121 patients with interdigital foot infections were examined directly with the use of 20% potassium hydroxide mounts and Gram stain under the microscope and cultured on Sabouraud's dextrose agar plates. In identification of superficial mycoses, the rate was found to be 14% with the cultural method and 14% with direct microscopic examination. Using a combination of direct microscopic examination and culture, a 33.8% ratio was achieved. In the culture of these samples, the most isolated factor was Trichophyton rubrum (33.7%. In 24 of the patients (19.8% Corynebacterium minutissimum was detected by Gram staining, in 6 of these patients Trichophyton rubrum was found, Trichophyton mentagrophytes was found in 2 and Trichosporon spp. was found in 1. The examination of interdigital foot lesions in the laboratory, the coexistence of erythrasma with dermatophytes and yeast should be considered.

  9. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  10. The MurC Ligase Essential for Peptidoglycan Biosynthesis Is Regulated by the Serine/Threonine Protein Kinase PknA in Corynebacterium glutamicum*

    OpenAIRE

    Fiuza, Maria; Canova, Marc J.; Patin, Delphine; Letek, Michal; Zanella-Cléon, Isabelle; Becchi, Michel; Mateos, Luís M.; Mengin-Lecreulx, Dominique; Molle, Virginie; Gil, José A.

    2008-01-01

    The Mur ligases play an essential role in the biosynthesis of bacterial cell-wall peptidoglycan and thus represent attractive targets for the design of novel antibacterials. These enzymes catalyze the stepwise formation of the peptide moiety of the peptidoglycan disaccharide peptide monomer unit. MurC is responsible of the addition of the first residue (l-alanine) onto the nucleotide precursor UDP-MurNAc. Phosphorylation of proteins by Ser/Thr protein kinases has recen...

  11. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  12. A microbiological and clinical review on Corynebacterium kroppenstedtii

    Directory of Open Access Journals (Sweden)

    Andreas Tauch

    2016-07-01

    Full Text Available The genus Corynebacterium represents a taxon of Gram-positive bacteria with a high G + C content in the genomic DNA. Corynebacterium kroppenstedtii is an unusual member of this taxon as it lacks the characteristic mycolic acids in the cell envelope. Genome sequence analysis of the C. kroppenstedtii type strain has revealed a lipophilic (lipid-requiring lifestyle and a remarkable repertoire of carbohydrate uptake and utilization systems. Clinical isolates of C. kroppenstedtii have been obtained almost exclusively from female patients and mainly from breast abscesses and cases of granulomatous mastitis. However, the role of C. kroppenstedtii in breast pathologies remains unclear. This review provides a comprehensive overview of the taxonomy, microbiology, and microbiological identification of C. kroppenstedtii, including polyphasic phenotypic approaches, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the use of 16S rRNA gene sequencing. A clinical review presents reported cases, various antimicrobial treatments, antibiotic susceptibility assays, and antibiotic resistance genes detected during genome sequencing. C. kroppenstedtii must be considered a potential opportunistic human pathogen and should be identified accurately in clinical laboratories.

  13. Evaluation of three methods for DNA fingerprinting of Corynebacterium pseudotuberculosis strains isolated from goats in Poland.

    Science.gov (United States)

    Stefańska, Ilona; Rzewuska, Magdalena; Binek, Marian

    2008-01-01

    Phenotypic approaches based on metabolic and biological characteristics of Corynebacterium pseudotuberculosis have been limited due to insufficient discrimination between closely related isolates. In this paper we present performance and convenience of three molecular typing methods: BOX-PCR, random amplification of polymorphic DNA (RAPD) and amplification of DNA fragments surrounding rare restriction site (ADSRRS-fingerprinting) in genome analysis of these bacteria. Among examined 61 strains there were distinguished four, eight and 10 different genotypes by BOX-PCR, RAPD and ADSRRS-fingerprinting, respectively. The value of discrimination index was the lowest for BOX-PCR (D = 0.265), much bigger for RAPD (D = 0.539) and the highest for ADSRRS-fingerprinting (D = 0.604). The good discriminatory ability and reproducibility of RAPD and ADSRRS-fingerprinting indicates that those techniques may be particularly applied for epidemiological studies of C. pseudotuberculosis isolates. We found that ADSRRS-fingerprinting is a rapid method offering good discrimination power, excellent reproducibility and may be applied for epidemiological studies of intraspecific genetic relatedness of C. pseudotuberculosis strains.

  14. Structure, function, and regulation of enzymes involved in amino acid metabolism of bacteria and archaea.

    Science.gov (United States)

    Tomita, Takeo

    2017-11-01

    Amino acids are essential components in all organisms because they are building blocks of proteins. They are also produced industrially and used for various purposes. For example, L-glutamate is used as the component of "umami" taste and lysine has been used as livestock feed. Recently, many kinds of amino acids have attracted attention as biological regulators and are used for a healthy life. Thus, to clarify the mechanism of how amino acids are biosynthesized and how they work as biological regulators will lead to further effective utilization of them. Here, I review the leucine-induced-allosteric activation of glutamate dehydrogenase (GDH) from Thermus thermophilus and the relationship with the allosteric regulation of GDH from mammals. Next, I describe structural insights into the efficient production of L-glutamate by GDH from an excellent L-glutamate producer, Corynebacterium glutamicum. Finally, I review the structural biology of lysine biosynthesis of thermophilic bacterium and archaea.

  15. Insight of Genus Corynebacterium: Ascertaining the Role of Pathogenic and Non-pathogenic Species.

    Science.gov (United States)

    Oliveira, Alberto; Oliveira, Leticia C; Aburjaile, Flavia; Benevides, Leandro; Tiwari, Sandeep; Jamal, Syed B; Silva, Arthur; Figueiredo, Henrique C P; Ghosh, Preetam; Portela, Ricardo W; De Carvalho Azevedo, Vasco A; Wattam, Alice R

    2017-01-01

    This review gathers recent information about genomic and transcriptomic studies in the Corynebacterium genus, exploring, for example, prediction of pathogenicity islands and stress response in different pathogenic and non-pathogenic species. In addition, is described several phylogeny studies to Corynebacterium , exploring since the identification of species until biological speciation in one species belonging to the genus Corynebacterium . Important concepts associated with virulence highlighting the role of Pld protein and Tox gene. The adhesion, characteristic of virulence factor, was described using the sortase mechanism that is associated to anchorage to the cell wall. In addition, survival inside the host cell and some diseases, were too addressed for pathogenic corynebacteria, while important biochemical pathways and biotechnological applications retain the focus of this review for non-pathogenic corynebacteria. Concluding, this review broadly explores characteristics in genus Corynebacterium showing to have strong relevance inside the medical, veterinary, and biotechnology field.

  16. Experimental transmission of Corynebacterium pseudotuberculosis biovar equi in horses by house flies

    Science.gov (United States)

    The route of Corynebacterium pseudotuberculosis infection in horses remains undetermined, but transmission by insects is suspected. Scientists from CMAVE and Auburn University investigated house flies (Musca domestica L.) as possible vectors. Three ponies were directly inoculated with C. pseudotuber...

  17. Complete genome sequence of Corynebacterium pseudotuberculosis Cp31, isolated from an Egyptian buffalo

    DEFF Research Database (Denmark)

    Silva, Artur; Ramos, Rommel Thiago Jucá; Ribeiro Carneiro, Adriana

    2012-01-01

    Corynebacterium pseudotuberculosis is of major veterinary importance because it affects many animal species, causing economically significant livestock diseases and losses. Therefore, the genomic sequencing of various lines of this organism, isolated from different hosts, will aid in the developm...

  18. Corynebacterium species: an uncommon agent of peritoneal dialysis-related peritonitis and a challenging treatment

    OpenAIRE

    Ferreira, Joel; Teixeira e Costa, Fernando; Ramos, Aura

    2015-01-01

    Introduction: Corynebacterium is a component of normal skin flora and it is responsible for an increasing incidence of nosocomial infections in the last decades. Peritonitis and exit-site infections caused by this microorganism are uncommon but have a significant clinical impact due to their high relapsing rate. The ideal therapeutic approach in these situations is not yet clearly defined. Methods: Retrospective analysis of Corynebacterium spp peritonitis in a peritoneal dialysis unit between...

  19. Comparison of antimicrobial susceptibilities of Corynebacterium species by broth microdilution and disk diffusion methods.

    Science.gov (United States)

    Weiss, K; Laverdière, M; Rivest, R

    1996-01-01

    Corynebacterium species are increasingly being implicated in foreign-body infections and in immunocompromised-host infections. However, there are no specific recommendations on the method or the criteria to use in order to determine the in vitro activities of the antibiotics commonly used to treat Corynebacterium infections. The first aim of our study was to compare the susceptibilities of various species of Corynebacterium to vancomycin, erythromycin, and penicillin by using a broth microdilution method and a disk diffusion method. Second, the activity of penicillin against our isolates was assessed by using the interpretative criteria recommended by the National Committee for Clinical Laboratory Standards for the determination of the susceptibility of streptococci and Listeria monocytogenes to penicillin. Overall, 100% of the isolates were susceptible to vancomycin, while considerable variations in the activities of erythromycin and penicillin were noted for the different species tested, including the non-Corynebacterium jeikeium species. A good correlation in the susceptibilities of vancomycin and erythromycin between the disk diffusion and the microdilution methods was observed. However, a 5% rate of major or very major errors was detected with the Listeria criteria, while a high rate of minor errors (18%) was noted when the streptococcus criteria were used. Our findings indicate considerable variations in the activities of erythromycin and penicillin against the various species of Corynebacterium. Because of the absence of definite recommendations, important discrepancies were observed between the methods and the interpretations of the penicillin activity. PMID:8849254

  20. [Skin and Soft Tissue Infections Due to Corynebacterium ulcerans - Case Reports].

    Science.gov (United States)

    Jenssen, Christian; Schwede, Ilona; Neumann, Volker; Pietsch, Cristine; Handrick, Werner

    2017-10-01

    History and clinical findings  We report on three patients suffering from skin and soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans strains. In all three patients, there was a predisposition due to chronic diseases. Three patients had domestic animals (cat, dog) in their households. Investigations and diagnosis  A mixed bacterial flora including Corynebacterium ulcerans was found in wound swab samples. Diphtheric toxin was produced by the Corynebacterium ulcerans strains in all three cases. Treatment and course  In all three patients, successful handling of the skin and soft tissue infections was possible by combining local treatment with antibiotics. Diphtheria antitoxin was not administered in any case. Conclusion  Based on a review of the recent literature pathogenesis, clinical symptoms and signs, diagnostics and therapy of skin and soft tissue infections due to Corynebacterium ulcerans are discussed. Corynebacterium ulcerans should be considered as a potential cause of severe skin and soft tissue infections. Occupational or domestic animal contacts should be evaluated. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Comparative evolutionary genomics of Corynebacterium with special reference to codon and amino acid usage diversities.

    Science.gov (United States)

    Pal, Shilpee; Sarkar, Indrani; Roy, Ayan; Mohapatra, Pradeep K Das; Mondal, Keshab C; Sen, Arnab

    2018-02-01

    The present study has been aimed to the comparative analysis of high GC composition containing Corynebacterium genomes and their evolutionary study by exploring codon and amino acid usage patterns. Phylogenetic study by MLSA approach, indel analysis and BLAST matrix differentiated Corynebacterium species in pathogenic and non-pathogenic clusters. Correspondence analysis on synonymous codon usage reveals that, gene length, optimal codon frequencies and tRNA abundance affect the gene expression of Corynebacterium. Most of the optimal codons as well as translationally optimal codons are C ending i.e. RNY (R-purine, N-any nucleotide base, and Y-pyrimidine) and reveal translational selection pressure on codon bias of Corynebacterium. Amino acid usage is affected by hydrophobicity, aromaticity, protein energy cost, etc. Highly expressed genes followed the cost minimization hypothesis and are less diverged at their synonymous positions of codons. Functional analysis of core genes shows significant difference in pathogenic and non-pathogenic Corynebacterium. The study reveals close relationship between non-pathogenic and opportunistic pathogenic Corynebaterium as well as between molecular evolution and survival niches of the organism.

  2. Corynebacterium species causing breast abscesses among patients attending a tertiary care hospital in Chennai, South India.

    Science.gov (United States)

    Poojary, Indira; Kurian, Ann; V A, Jayalekshmi; Devapriya J, Debora; M A, Thirunarayan

    2017-07-01

    Corynebacterium species other than Corynebacterium diphtheriae were mostly considered contaminants in the past, but there are reports of their association with wide variety of human infections lately. In this study, we look into Corynebacterium species isolated from breast abscess patients and assess their antimicrobial susceptibility pattern and treatment outcomes. Pus samples from suspected breast abscess cases were examined from October 2014 to September 2015. Growth of Gram-positive bacilli morphologically resembling Corynebacterium species were identified by matrix-assisted laser desorption/ionization- time of flight mass spectrometry identifications generated by the Vitek MS system (bioMérieux, France) (MALDI-TOF Vitek MS system) and antimicrobial susceptibility was done. Corynebacterium species were isolated from 10 female breast abscess patients with median age of 36 years (range 25-59 years). Out of the 10 isolates four isolates were identified as C. kroppenstedtii; one isolate as C. striatum and five isolates were identified as C. amycolatum/C.xerosis. Out of four isolates of C .kroppenstedtii, two isolates were resistant to cotrimoxazole and one C. striatum isolate was resistant to penicillin, ampicillin, cotrimoxazole and clindamycin. Of the five isolates identified as C amycolatum/C xerosis, all were sensitive to vancomycin and linezolid but resistant to clindamycin. All the patients were treated with incision, drainage and antibiotics based on the sensitivity pattern; eight were cured and two patients did not come for follow-up. Corynebacterium species should be considered one of the causative agents of breast abscess and a varied susceptibility profile amongst the different species makes susceptibility testing important. Identification by MALDI-TOF Vitek MS system may not differentiate between C. amycolatum and C. xerosis.

  3. Tips and tricks for the assembly of a Corynebacterium pseudotuberculosis genome using a semiconductor sequencer

    DEFF Research Database (Denmark)

    Ramos, Rommel Thiago Jucá; Carneiro, Adriana Ribeiro; Soares, Siomar de Castro

    2013-01-01

    that enable reference-based assembly, such as the one used in the present study, Corynebacterium pseudotuberculosis biovar equi, which causes high economic losses in the US equine industry. The quality treatment strategy incorporated into the assembly pipeline enabled a 16-fold greater use of the sequencing...... was validated by comparative genomics with other species of the genus Corynebacterium. The present study presents a modus operandi that enables a greater and better use of data obtained from semiconductor sequencing for obtaining the complete genome from a prokaryotic microorganism, C. pseudotuberculosis, which...

  4. Fatal case of bacteremia caused by an atypical strain of Corynebacterium mucifaciens

    Directory of Open Access Journals (Sweden)

    Vlademir Vicente Cantarelli

    Full Text Available Corynebacterium species have often been considered normal skin flora or contaminants; however, in recent years they have been increasingly implicated in serious infections. Moreover, many new species have been discovered and old species renamed, especially after molecular biology techniques were introduced. Corynebacterium mucifaciens is mainly isolated from blood and from other normally-sterile body fluids; it forms slightly yellow, mucoid colonies on blood agar. We report a fatal case of bacteremia due to an atypical strain of C. mucifaciens. This strain had atypical colony morphology; analysis of the 16S rRNA gene was used to define the species.

  5. Rapid detection of Corynebacterium pseudotuberculosis in clinical samples from sheep.

    Science.gov (United States)

    Kumar, Jyoti; Tripathi, Bhupendra Nath; Kumar, Rajiv; Sonawane, Ganesh Gangaram; Dixit, Shivendra Kumar

    2013-08-01

    Corynebacterium pseudotuberculosis, a Gram-positive bacterium is the causative agent of caseous lymphadenitis (CLA), a chronic disease of sheep, goats and other warm blooded animals. In the present study, a total of 1,080 sheep reared under semi-intensive system on organized farms situated in the semi arid tropical region of Rajasthan, India, was clinically examined. Pus samples from superficial lymph nodes of 25 (2.31%) adult sheep showing clinical lesions similar to CLA were collected for laboratory analyses. On the basis of morphological, cultural and biochemical characteristics 12 (48%) bacterial isolates from pus identified it as C. pseudotuberculosis. A polymerase chain reaction (PCR) assay targeting Putative oligopeptide/dipeptide ABC transporter, nicotinamide adenine dinucleotide phosphate (NADP) oxidoreductase coenzyme F420-dependent and proline iminopeptidase (PIP) genes of C. pseudotuberculosis was developed that showed 14 pus samples as positive. All C. pseudotuberculosis isolates were also found positive for these genes in the PCR. The specificity of the PCR products was confirmed by sequencing of the amplified products that showed 98-100% homology with published sequences available in the NCBI database. The present study shows the incidence of CLA as 2.31%, 1.1% and 1.29% based on clinical, bacterial culture and direct pus PCR assay, respectively. The PCR assay was rapid, specific and as significant as bacterial culture in detecting bacteria directly in the clinical pus samples. The PCR assay developed in the study can be applied for the diagnosis and control of CLA. Furthermore, the assay can also be applied to detect C. pseudotuberculosis in various clinical samples.

  6. Activity of disinfectants and biofilm production of Corynebacterium pseudotuberculosis

    Directory of Open Access Journals (Sweden)

    Maria da C.A. Sá

    2013-11-01

    Full Text Available To verify the occurrence of caseous lymphadenitis in sheep and goats on farms of Pernambuco, Brazil, and in animals slaughtered in two Brazilian cities (Petrolina/PE and Juazeiro/BA, and to characterize the susceptibility profile of Corynebacterium pseudotuberculosis to disinfectants and antimicrobials, and its relationship with biofilm production were the objectives of this study. 398 samples were tested for sensitivity to antimicrobial drugs, disinfectants, and biofilm production. Among the 108 samples collected on the properties, 75% were positive for C. pseudotuberculosis. Slaughterhouse samples indicated an occurrence of caseous lymphadenitis in 15.66% and 6.31% for animals slaughtered in Petrolina and Juazeiro respectively. With respect to antimicrobials, the sensitivity obtained was 100% for florfenicol and tetracycline; 99.25% for enrofloxacin, ciprofloxacin and lincomycin; 98.99% for cephalothin; 98.74% for norfloxacin and sulfazotrim; 97.74% for gentamicin; 94.22% for ampicillin; 91.71% for amoxicillin; 91.21% for penicillin G; 89.19% for neomycin and 0% for novobiocin. In analyzes with disinfectants, the efficiency for chlorhexidine was 100%, 97.20% for quaternary ammonium, 87.40% for chlorine and 84.40% for iodine. 75% of the isolates were weak or non-biofilm producers. For the consolidated biofilm, found that iodine decreased biofilm formation in 13 isolates and quaternary ammonia in 11 isolates. The reduction of the biofilm formation was observed for iodine and quaternary ammonium in consolidated biofilm formation in 33% and 28% of the isolates, respectively. The results of this study highlight the importance of establishing measures to prevent and control the disease.

  7. Molecular epidemiology of Corynebacterium pseudotuberculosis isolated from horses in California.

    Science.gov (United States)

    Haas, Dionei J; Dorneles, Elaine M S; Spier, Sharon J; Carroll, Scott P; Edman, Judy; Azevedo, Vasco A; Heinemann, Marcos B; Lage, Andrey P

    2017-04-01

    Corynebacterium pseudotuberculosis biovar Equi is an important pathogen of horses. It is increasing in frequency in the United States, and is responsible for various clinical forms of infection, including external abscesses, internal abscesses of the abdominal or thoracic cavities, and ulcerative lymphangitis. The host/pathogen factors dictating the form or severity of infection are currently unknown. Our recent investigations have shown that genotyping C. pseudotuberculosis isolates using enterobacterial repetitive intergenic consensus (ERIC)-PCR is useful for understanding the evolutionary genetics of the species as well for molecular epidemiology studies. The aims of the present study were to assess (i) the genetic diversity of C. pseudotuberculosis strains isolated from horses in California, United States and (ii) the epidemiologic relationships among isolates. One hundred and seven C. pseudotuberculosis biovar Equi isolates from ninety-five horses, and two C. pseudotuberculosis biovar Ovis strains, C. pseudotuberculosis ATCC 19410 T type strain and C. pseudotuberculosis 1002 vaccine strain, were fingerprinted using the ERIC 1+2-PCR. C. pseudotuberculosis isolated from horses showed a high genetic diversity, clustering in twenty-seven genotypes with a diversity index of 0.91. Minimal spanning tree showed four major clonal complexes with a pattern of temporal clustering. Strains isolated from the same horse showed identical ERIC 1+2-PCR genotype, with the exception of two strains isolated from the same animal that showed distinct genotypes, suggesting a co-infection. We found no strong genetic signals related to clinical form (including internal versus external infections). However, temporal clustering of genotypes was observed. Copyright © 2016. Published by Elsevier B.V.

  8. Corynebacterium renale as a cause of reactions to the complement fixation test for Johne's disease

    NARCIS (Netherlands)

    Gilmour, N.J.L.; Goudswaard, J.

    Complement fixation (C.F.) tests and fluorescent antibody (F.A.) tests were carried out on sera from rabbits inoculated with Corynebacterium renale and Mycobacterium johnei, and on sera from cattle with C. renale pyelonephritis and with Johne's disease. Cross-reactions were a feature of the C.F.

  9. An unusual etiological agent of implantable cardioverter device endocarditis: Corynebacterium mucifaciens

    Directory of Open Access Journals (Sweden)

    Adnan Kaya

    2016-03-01

    Full Text Available Cardiac pacing devices and implantable cardioverter defibrillator (ICD are becoming the mainstay of therapy in cardiology and infective endocarditis (IE and pocket infection; however, these devices require careful monitoring. Here, we describe a case of a 68-year-old female with an ICD presenting with a previously unknown etiological agent of IE, Corynebacterium mucifaciens.

  10. Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study.

    LENUS (Irish Health Repository)

    Wagner, K S

    2011-04-01

    Diphtheria is now rare in most European countries but, when cases do arise, the case fatality rate is high (5-10%). Because few countries continue to routinely screen for the causative organisms of diphtheria, the extent to which they are circulating amongst different European populations is largely unknown. During 2007-2008, ten European countries each screened between 968 and 8551 throat swabs from patients with upper respiratory tract infections. Six toxigenic strains of Corynebacterium diphtheriae were identified: two from symptomatic patients in Latvia (the country with the highest reported incidence of diphtheria in the European Union) and four from Lithuania (two cases, two carriers); the last reported case of diphtheria in Lithuania was in 2002. Carriage rates of non-toxigenic organisms ranged from 0 (Bulgaria, Finland, Greece, Ireland, Italy) to 4.0 per 1000 (95% CI 2.0-7.1) in Turkey. A total of 28 non-toxigenic strains were identified during the study (26 C. diphtheriae, one Corynebacterium ulcerans, one Corynebacterium pseudotuberculosis). The non-toxigenic C. ulcerans strain was isolated from the UK, the country with the highest reported incidence of cases due to C. ulcerans. Of the eleven ribotypes detected, Cluj was seen most frequently in the non-toxigenic isolates and, amongst toxigenic isolates, the major epidemic clone, Sankt-Petersburg, is still in circulation. Isolation of toxigenic C. diphtheriae and non-toxigenic C. diphtheriae and C. ulcerans in highly-vaccinated populations highlights the need to maintain microbiological surveillance, laboratory expertise and an awareness of these organisms amongst public health specialists, microbiologists and clinicians.

  11. POTENSI GEN dtx DAN dtxR SEBAGAI MARKER UNTUK DETEKSI DAN PEMERIKSAAN TOKSIGENISITAS Corynebacterium diphtheriae

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    Sunarno Sunarno

    2013-05-01

    Full Text Available Abstract.   Corynebacterium diphtheriae is the causative agent of diphtheria. The main virulence determinant of the bacteria is diphtheria toxin, the cause of the systemic complication seen with diphtheria. Production of diphtheria toxin by toxigenic strain encoded by dtx/tox gene and repressed by dtxR gene. Gold standard for bacterial toxigenicity test carried out by conventional methods (Elek test, Guinea pig and vero cell cytotoxicity. However, Elek test have variety result, time consume and problem of the reagent availability. On the other hand, the animal (Guinea pig testing was opposed by many animal lovers and the vero cell cytotoxicity test require high cost. The study purposed to evaluate the using of dtx and dtxR genes as a detection marker of C.diphtheriae and bacterial toxigenicity test simultaneusly by Multiplex PCR. The study examined 44 bacterial and fungal isolates, included 22 C.diphtheriae (4 reference strains and 18 clinical isolates, 5 other specieses of Corynebacterium  (reference strains and 17 non-Corynebacterium (10 reference strains and 7 stock cultures . All of sample were examined by Multiplex PCR for 2 primer pairs targeted dtx and dtxR genes. The study showed that the Multiplex PCR for dtx and dtxR as target genes able to detect all of sample correctly thus concluded that dtx and dtxR genes could be used as a marker for alternative detection and toxigenicity test of C.diphtheriae by Multiplex PCR rapidly and accuratelly. Key words: Corynebacterium diphtheriae, dtx, dan dtxR Abstrak. Corynebacterium diphtheriae merupakan agen penyebab penyakit difteri.. Faktor virulensi utama  C. diphtheriae adalah toksigenisitas (kemampuan memproduksi toksin bakteri toxin. Produksi toksin diatur seperangkat gen yang disebut gen tox/dtx dan diregulasi oleh gen dtxR. Gold standard untuk pemeriksaan toksigenisitas C.diphtheriae adalah dengan metode konvensional (Elek test, Guinea pig dan vero cell cytotoxigenicity,namun  Elek test

  12. Complete genome sequence of Corynebacterium variabile DSM 44702 isolated from the surface of smear-ripened cheeses and insights into cheese ripening and flavor generation

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    Trost Eva

    2011-11-01

    Full Text Available Abstract Background Corynebacterium variabile is part of the complex microflora on the surface of smear-ripened cheeses and contributes to the development of flavor and textural properties during cheese ripening. Still little is known about the metabolic processes and microbial interactions during the production of smear-ripened cheeses. Therefore, the gene repertoire contributing to the lifestyle of the cheese isolate C. variabile DSM 44702 was deduced from the complete genome sequence to get a better understanding of this industrial process. Results The chromosome of C. variabile DSM 44702 is composed of 3, 433, 007 bp and contains 3, 071 protein-coding regions. A comparative analysis of this gene repertoire with that of other corynebacteria detected 1, 534 predicted genes to be specific for the cheese isolate. These genes might contribute to distinct metabolic capabilities of C. variabile, as several of them are associated with metabolic functions in cheese habitats by playing roles in the utilization of alternative carbon and sulphur sources, in amino acid metabolism, and fatty acid degradation. Relevant C. variabile genes confer the capability to catabolize gluconate, lactate, propionate, taurine, and gamma-aminobutyric acid and to utilize external caseins. In addition, C. variabile is equipped with several siderophore biosynthesis gene clusters for iron acquisition and an exceptional repertoire of AraC-regulated iron uptake systems. Moreover, C. variabile can produce acetoin, butanediol, and methanethiol, which are important flavor compounds in smear-ripened cheeses. Conclusions The genome sequence of C. variabile provides detailed insights into the distinct metabolic features of this bacterium, implying a strong adaption to the iron-depleted cheese surface habitat. By combining in silico data obtained from the genome annotation with previous experimental knowledge, occasional observations on genes that are involved in the complex

  13. An unusual case of chronic nonhealing periorbital ulceration due to a new species of Corynebacterium sp. strain UCL557

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    Bipasa Chakraborty

    2016-01-01

    Full Text Available Nondiphtherial Corynebacterium (diphtheroids has been related to blood and wound infections but are an uncommon cause for soft tissue infection. We report a case of periorbital soft tissue infection with ulceration caused by multidrug-resistant Corynebacterium spp. in a 9-year-old girl who is apparently immunocompetant. Computed tomography scan showed soft tissue involvement of right periorbital region with no bony destructions or focal calcifications. Vision remained unaffected. Patient was treated by debridement and skin grafting, but condition did not improve. Pus collected from the periorbital ulcerated area was cultured in blood agar and Corynebacterium spp. was isolated from the pure culture, which was identified as a new species Corynebacterium sp. strain UCL557 using 16S rDNA- based molecular technique based on nucleotide homology and phylogenetic analysis. Antibiogram showed multiresistance pattern with sensitivity to ceftriaxone-sulbactum vancomycin and linezolid. After initiation of treatment with vancomycin infusion and oral linezolid, the patient responded well and lesion started to heal. To the best of our knowledge, this is the first ever case report of periorbital ulceration by new species of Corynebacterium sp. strain UCL557.

  14. Microbial production of lysine from sustainable feedstock

    DEFF Research Database (Denmark)

    Wang, Zhihao; Grishkova, Maria; Solem, Christian

    2014-01-01

    Lysine is produced in a fermentation process using Corynebacterium glutamicum. And even though production strains have been improved for decades, there is still room for further optimization.......Lysine is produced in a fermentation process using Corynebacterium glutamicum. And even though production strains have been improved for decades, there is still room for further optimization....

  15. Microbe Profile: Corynebacterium diphtheriae - an old foe always ready to seize opportunity.

    Science.gov (United States)

    Hoskisson, Paul A

    2018-02-21

    Corynebacterium diphtheriae is a globally important Gram-positive aerobic Actinobacterium capable of causing the toxin-mediated disease, diphtheria. Diphtheria was a major cause of childhood mortality prior to the introduction of the toxoid vaccine, yet it is capable of rapid resurgence following the breakdown of healthcare provision, vaccination or displacement of people. The mechanism and treatment of toxin-mediated disease is well understood, however there are key gaps in our knowledge on the basic biology of C. diphtheriae particularly relating to host colonisation, the nature of asymptomatic carriage, population genomics and host adaptation.

  16. Toxigenic Corynebacterium ulcerans isolated from a free-roaming red fox (Vulpes vulpes).

    Science.gov (United States)

    Sting, Reinhard; Ketterer-Pintur, Sandra; Contzen, Matthias; Mauder, Norman; Süss-Dombrowski, Christine

    2015-01-01

    Corynebacterium (C.) ulcerans could be isolated from the spleen of a red fox (Vulpes vulpes) that had been found dead in the state of Baden-Württemberg, Germany. Pathohistological examination suggested that the fox had died of distemper, as was confirmed by PCR. The isolate was identified biochemically, by MALDI-TOF MS, FT-IR and by partial 16S rRNA, rpoB and tox gene sequencing. Using the Elek test the C. ulcerans isolate demonstrated diphtheria toxin production. FT-IR and sequencing data obtained from the C. ulcerans isolate from the red fox showed higher similarity to isolates from humans than to those from wild game.

  17. Structural Basis of a Thiol-Disulfide Oxidoreductase in the Hedgehog-Forming Actinobacterium Corynebacterium matruchotii.

    Science.gov (United States)

    Luong, Truc Thanh; Tirgar, Reyhaneh; Reardon-Robinson, Melissa E; Joachimiak, Andrzej; Osipiuk, Jerzy; Ton-That, Hung

    2018-05-01

    The actinobacterium Corynebacterium matruchotii has been implicated in nucleation of oral microbial consortia leading to biofilm formation. Due to the lack of genetic tools, little is known about basic cellular processes, including protein secretion and folding, in this organism. We report here a survey of the C. matruchotii genome, which encodes a large number of exported proteins containing paired cysteine residues, and identified an oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA (MdbA Cd ). Crystallization studies uncovered that the 1.2-Å resolution structure of C. matruchotii MdbA (MdbA Cm ) possesses two conserved features found in actinobacterial MdbA enzymes, a thioredoxin-like fold and an extended α-helical domain. By reconstituting the disulfide bond-forming machine in vitro , we demonstrated that MdbA Cm catalyzes disulfide bond formation within the actinobacterial pilin FimA. A new gene deletion method supported that mdbA is essential in C. matruchotii Remarkably, heterologous expression of MdbA Cm in the C. diphtheriae Δ mdbA mutant rescued its known defects in cell growth and morphology, toxin production, and pilus assembly, and this thiol-disulfide oxidoreductase activity required the catalytic motif CXXC. Altogether, the results suggest that MdbA Cm is a major thiol-disulfide oxidoreductase, which likely mediates posttranslocational protein folding in C. matruchotii by a mechanism that is conserved in Actinobacteria IMPORTANCE The actinobacterium Corynebacterium matruchotii has been implicated in the development of oral biofilms or dental plaque; however, little is known about the basic cellular processes in this organism. We report here a high-resolution structure of a C. matruchotii oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA. By biochemical analysis, we demonstrated that C. matruchotii MdbA catalyzes disulfide

  18. Recurrent Breast Abscesses due to Corynebacterium kroppenstedtii, a Human Pathogen Uncommon in Caucasian Women

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    Anne Le Flèche-Matéos

    2012-01-01

    Full Text Available Background. Corynebacterium kroppenstedtii (Ck was first described in 1998 from human sputum. Contrary to what is observed in ethnic groups such as Maori, Ck is rarely isolated from breast abscesses and granulomatous mastitis in Caucasian women. Case Presentation. We herein report a case of recurrent breast abscesses in a 46-year-old Caucasian woman. Conclusion. In the case of recurrent breast abscesses, even in Caucasian women, the possible involvement of Ck should be investigated. The current lack of such investigations, probably due to the difficulty to detect Ck, may cause the underestimation of such an aetiology.

  19. First report of Corynebacterium pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig (Sus scrofa domesticus).

    Science.gov (United States)

    Oliveira, Manuela; Barroco, Cynthia; Mottola, Carla; Santos, Raquel; Lemsaddek, Abdelhak; Tavares, Luis; Semedo-Lemsaddek, Teresa

    2014-09-21

    Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis, a common disease in small ruminant populations throughout the world and responsible for a significant economic impact for producers. To our knowledge, this is the first characterization of C. pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig (Sus scrofa domesticus). In this study, phenotypic and genotypic identification methods allocated the swine isolates in C. pseudotuberculosis biovar ovis. The vast majority of the isolates were able to produce phospholipase D and were susceptible to most of the antimicrobial compounds tested. Macrorestriction patterns obtained by Pulsed Field Gel Electrophoresis (PFGE) grouped the C. pseudotuberculosis in two clusters with a high similarity index, which reveals their clonal relatedness. Furthermore, swine isolates were compared with C. pseudotuberculosis from caprines and PFGE patterns also showed high similarity, suggesting the prevalence of dominant clones and a potential cross-dissemination between these two animal hosts. This work represents the first report of Corynebacterium pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig and alerts for the importance of the establishment of suitable control and sanitary management practices to control the infection and avoid further dissemination of this important pathogen to other animal hosts.

  20. Characterization of Staphylococcus and Corynebacterium clusters in the human axillary region.

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    Chris Callewaert

    Full Text Available The skin microbial community is regarded as essential for human health and well-being, but likewise plays an important role in the formation of body odor in, for instance, the axillae. Few molecular-based research was done on the axillary microbiome. This study typified the axillary microbiome of a group of 53 healthy subjects. A profound view was obtained of the interpersonal, intrapersonal and temporal diversity of the human axillary microbiota. Denaturing gradient gel electrophoresis (DGGE and next generation sequencing on 16S rRNA gene region were combined and used as extent to each other. Two important clusters were characterized, where Staphylococcus and Corynebacterium species were the abundant species. Females predominantly clustered within the Staphylococcus cluster (87%, n = 17, whereas males clustered more in the Corynebacterium cluster (39%, n = 36. The axillary microbiota was unique to each individual. Left-right asymmetry occurred in about half of the human population. For the first time, an elaborate study was performed on the dynamics of the axillary microbiome. A relatively stable axillary microbiome was noticed, although a few subjects evolved towards another stable community. The deodorant usage had a proportional linear influence on the species diversity of the axillary microbiome.

  1. Genome sequence of Corynebacterium pseudotuberculosis biovar equi strain 258 and prediction of antigenic targets to improve biotechnological vaccine production

    DEFF Research Database (Denmark)

    Soares, Siomar C; Trost, Eva; Ramos, Rommel T J

    2013-01-01

    Corynebacterium pseudotuberculosis is the causative agent of several veterinary diseases in a broad range of economically important hosts, which can vary from caseous lymphadenitis in sheep and goats (biovar ovis) to ulcerative lymphangitis in cattle and horses (biovar equi). Existing vaccines ag...

  2. Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation.

    Science.gov (United States)

    Xu, Meijuan; Qin, Jingru; Rao, Zhiming; You, Hengyi; Zhang, Xian; Yang, Taowei; Wang, Xiaoyuan; Xu, Zhenghong

    2016-01-19

    Corynebacterium crenatum SYPA 5 is the industrial strain for L-arginine production. Poly-β-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and L-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the L-arginine biosynthesis in C. crenatum SYPA 5. C. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of L-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L L-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key L-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9-3.0 times compared with the parent strain. Accumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time L-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular L

  3. Brain and lung cryptococcoma and concurrent corynebacterium pseudotuberculosis infection in a goat: a case report

    Directory of Open Access Journals (Sweden)

    MCR Luvizotto

    2009-01-01

    Full Text Available A four-year-old male goat with a history of neurological disorder was euthanized. It presented uncommon nodules in the brain and lungs associated with multiple abscesses, predominantly in the spleen and liver. Histological examination of brain and lung sections revealed yeast forms confirmed to be Cryptococcus gattii after a combination of isolation and polymerase chain reaction (PCR procedures. Moreover, Corynebacterium pseudotuberculosis infection was diagnosed by PCR of samples from the lung, spleen and liver. The present report highlights the rare concurrent infection of C. gatti and C. pseudotuberculosis in an adult goat from São Paulo state, Brazil, and indicates the necessity of surveillance in the treatment of goats with atypical pulmonary infections associated with neurological disorders.

  4. In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein

    DEFF Research Database (Denmark)

    Folador, Edson Luiz; de Carvalho, Paulo Vinícius Sanches Daltro; Silva, Wanderson Marques

    2016-01-01

    BACKGROUND: Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation...... of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were...... not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous. CONCLUSIONS: The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing...

  5. Influence of Corynebacterium parvum on the phagocytosis of /sup 198/Au colloids in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bergoc, R.M.; Bianchin, A.M.; Caro, R.A.; Ihlo, J.E.; Rivera, E.S. (Buenos Aires Univ. Nacional (Argentina). Facultad de Farmacia y Bioquimica)

    1982-07-01

    The kinetics of the phagocytosis of gelatin-protected /sup 198/Au colloids in Wistar rats treated with Corynebacterium Parvum (CBP), was studied in order to explain its mechanism of immunomodulation. A previously developed extracorporeal blood circulation technique was used. The changes in the rate of phagocytosis, v, after the administration of CBP, for a dose of the /sup 198/Au colloid smaller or higher than the substratum constant, were studied. In the first case, no significant changes of v were observed; in the second case, significant increases of v were determined, which reached a maximum 6 days after the CBP administration. The kinetic analysis of the obtained data indicates that the action of CBP is exerted on the stage of the entrance of the colloidal particle into the reticuloendothelial cell.

  6. Influence of Corynebacterium parvum on the phagocytosis of 198Au colloids in rats

    International Nuclear Information System (INIS)

    Bergoc, R.M.; Bianchin, A.M.; Caro, R.A.; Ihlo, J.E.; Rivera, E.S.

    1982-01-01

    The kinetics of the phagocytosis of gelatin-protected 198 Au colloids in Wistar rats treated with Corynebacterium Parvum (CBP), was studied in order to explain its mechanism of immunomodulation. A previously developed extracorporeal blood circulation technique was used. The changes in the rate of phagocytosis, v, after the administration of CBP, for a dose of the 198 Au colloid smaller or higher than the substratum constant, were studied. In the first case, no significant changes of v were observed; in the second case, significant increases of v were determined, which reached a maximum 6 days after the CBP administration. The kinetic analysis of the obtained data indicates that the action of CBP is exerted on the stage of the entrance of the colloidal particle into the reticuloendothelial cell. (author) [es

  7. Pathogenicity and genetic variation of 3 strains of Corynebacterium bovis in immunodeficient mice.

    Science.gov (United States)

    Dole, Vandana S; Henderson, Kenneth S; Fister, Richard D; Pietrowski, Michael T; Maldonado, Geomaris; Clifford, Charles B

    2013-07-01

    Corynebacterium bovis has been associated with hyperkeratotic dermatitis and acanthosis in mice. We studied 3 different strains of C. bovis: one previously described to cause hyperkeratotic dermatitis (HAC), one that infected athymic nude mice without leading to the classic clinical signs, and one of bovine origin (ATCC 7715). The 3 strains showed a few biochemical and genetic differences. Immunodeficient nude mice were housed in 3 independent isolators and inoculated with pure cultures of the 3 strains. We studied the transmission of these C. bovis studies to isolator-bedding and contact sentinels housed for 5 to 12 wk in filter-top or wire-top cages in the respective isolators. Using a 16S rRNA-based qPCR assay, we did not find consistent differences in growth and transmission among the 3 C. bovis strains, and neither the incidence nor severity of hyperkeratosis or acanthosis differed between strains. Housing in filter-top compared with wire-top cages did not alter the morbidity associated with any of the strains. Our findings confirmed the variability in the gross and histologic changes associated with C. bovis infection of mice. Although bacteriology was a sensitive method for the detection of Corynebacterium spp., standard algorithms occasionally misidentified C. bovis and several related species. Our study demonstrates that PCR of skin swabs or feces is a sensitive and specific method for the detection of C. bovis infection in mice. An rpoB-based screen of samples from North American vivaria revealed that HAC is the predominant C. bovis strain in laboratory mice.

  8. Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

    Directory of Open Access Journals (Sweden)

    Silvana Vargas Superti

    2009-04-01

    Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

  9. Determination of the Presence of crpgenes in Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus delbrueckii and Corynebacterium veraSuş

    OpenAIRE

    BELDÜZ, Ali Osman; DEMİRBAĞ, Zihni; DÜLGER, Sabriye

    2014-01-01

    Polymerase chain reaction (PCR) was employed to detect the presence of cyclic AMP receptor protein (CPR) in a number of diverse organisms. In PCR, two primers specific to the crp gene of Escherichia coli were used. Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus delbrueckii and Corynebacterium veraSuş all showed the same size of PCR frağments (708 bp) and same restriction frağment length polymorphizm (RFLP).

  10. Difteria pelo Corynebacterium ulcerans: uma zoonose emergente no Brasil e no mundo

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    Alexandre Alves de Souza de Oliveira Dias

    2011-12-01

    Full Text Available O artigo revisa a literatura sobre a emergência de infecções humanas causadas por Corynebacterium ulcerans em diversos países, incluindo o Brasil. Foi realizada análise de artigos publicados entre 1926 e 2011 nas bases Medline/PubMed e SciELO, bem como artigos e informes do Ministério da Saúde. Apresenta-se um esquema de triagem, rápido, econômico e de fácil execução, capaz de permitir a realização do diagnóstico presuntivo de C. ulcerans e C. diphtheriae na maioria dos laboratórios brasileiros públicos e privados. A circulação de C. ulcerans em vários países, aliada aos recentes casos de isolamento do patógeno no Rio de Janeiro, é um alerta a clínicos, veterinários e microbiologistas sobre a ocorrência de difteria zoonótica e a circulação do C. ulcerans em regiões urbanas e rurais do território nacional e/ou da América Latina.

  11. Surgical Site Infection by Corynebacterium macginleyi in a Patient with Neurofibromatosis Type 1

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    Bruno Cacopardo

    2013-01-01

    Full Text Available Corynebacterium (C. macginleyi is a gram positive, lipophilic rod, usually considered a colonizer of skin and mucosal surfaces. Several reports have associated C. macginleyi with ocular infections, such as conjunctivitis and endophthalmitis. However, even if rare, extraocular infections from C. macginleyi may occur, especially among immunocompromised patients and patients with indwelling medical devices. We report herein the first case of surgical site infection by C. macginleyi after orthopaedic surgery for the correction of kyphoscoliosis in a patient with neurofibromatosis type 1. Our patient developed a nodular granulomatous lesion of about two centimetres along the surgical scar, at the level of C4-C5, with purulent discharge and formation of a fistulous tract. Cervical magnetic resonance imaging showed the presence of a two-centimetre fluid pocket in the subcutaneous tissue. Several swabs were collected from the borders of the lesion as well as from the exudate, with isolation of C. macginleyi. The isolate was susceptible to beta-lactams, cotrimoxazole, linezolid, and glycopeptides but resistant to quinolones, third-generation cephalosporins, and erythromycin. Two 30-day courses of antibiotic therapy with amoxicillin/clavulanate (1 g three times/day and cotrimoxazole (800/160 mg twice a day were administered, obtaining a complete healing of the lesion.

  12. Comparison of two biochemical methods for identifying Corynebacterium pseudotuberculosis isolated from sheep and goats.

    Science.gov (United States)

    Huerta, Belén; Gómez-Gascón, Lidia; Vela, Ana I; Fernández-Garayzábal, José F; Casamayor, Almudena; Tarradas, Carmen; Maldonado, Alfonso

    2013-06-01

    The biochemical pattern of Cowan and Steel (BPCS) was compared with a commercial biochemical strip for the identification of Corynebacterium pseudotuberculosis isolated from small ruminants. On 16S rRNA gene sequencing, 40/78 coryneform isolates from the lymph nodes of sheep and goats with lesions resembling caseous lymphadenitis were identified as C. pseudotuberculosis. The sensitivities of the BPCS and the commercial biochemical strip relative to 16S rRNA sequencing were 80% and 85%, and their specificities were 92.1% and 94.7%, respectively; the level of agreement between the BPCS and the commercial biochemical strip was high (κ=0.82). Likelihood ratios for positive and negative results were 10.0 and 0.22 for the BPCS, and 16.0 and 0.16 for the commercial biochemical strip, respectively. These results indicate that the BPCS and the commercial biochemical strip are both useful for identifying C. pseudotuberculosis in veterinary microbiology laboratories. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Aggregative adherent strains of Corynebacterium pseudodiphtheriticum enter and survive within HEp-2 epithelial cells

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    Monica Cristina de Souza

    2012-06-01

    Full Text Available Corynebacterium pseudodiphtheriticum is a well-known human pathogen that mainly causes respiratory disease and is associated with high mortality in compromised hosts. Little is known about the virulence factors and pathogenesis of C. pseudodiphtheriticum. In this study, cultured human epithelial (HEp-2 cells were used to analyse the adherence pattern, internalisation and intracellular survival of the ATCC 10700 type strain and two additional clinical isolates. These microorganisms exhibited an aggregative adherence-like pattern to HEp-2 cells characterised by clumps of bacteria with a "stacked-brick" appearance. The differences in the ability of these microorganisms to invade and survive within HEp-2 cells and replicate in the extracellular environment up to 24 h post infection were evaluated. The fluorescent actin staining test demonstrated that actin polymerisation is involved in the internalisation of the C. pseudodiphtheriticum strains. The depolymerisation of microfilaments by cytochalasin E significantly reduced the internalisation of C. pseudodiphtheriticum by HEp-2 cells. Bacterial internalisation and cytoskeletal rearrangement seemed to be partially triggered by the activation of tyrosine kinase activity. Although C. pseudodiphtheriticum strains did not demonstrate an ability to replicate intracellularly, HEp-2 cells were unable to fully clear the pathogen within 24 h. These characteristics may explain how some C. pseudodiphtheriticum strains cause severe infection in human patients.

  14. Mural endocarditis caused by Corynebacterium mustelae in a dog with a VSD.

    Science.gov (United States)

    Winter, Randolph L; Gordon, Sonya G; Zhang, Shuping; Hariu, Crystal D; Miller, Matthew W

    2014-01-01

    A 6 yr old female spayed large Munsterlander was evaluated following a 3 wk history of lethargy, inappetence, intermittent fever, and a recent change to the timing of her previously diagnosed heart murmur. Physical examination revealed marked dehydration, lethargy, and a grade 5/6 to-and-fro heart murmur that was auscultated best at the right sternal border. The dog was febrile, and echocardiography revealed a large, mobile, vegetative lesion in the right ventricular outflow tract associated with a ventricular septal defect (VSD). Mild aortic insufficiency was present. Corynebacterium mustelae (C. mustelae) was isolated from a pooled blood culture. Treatment of infective endocarditis (IE) was initiated along with supportive care, and the patient was discharged 9 days later. The dog remained without clinical signs 132 days after discharge. VSD is rarely mentioned as a predisposing factor for development of IE in veterinary literature; however, this report highlights that dogs with a VSD may be at risk for IE. To the authors' knowledge, this is the first documented case of a canine infection with C. mustelae. Infection with C. mustelae in this case represents a novel agent for IE in the dog.

  15. Crystallization and preliminary X-ray diffraction studies of FAD synthetase from Corynebacterium ammoniagenes

    International Nuclear Information System (INIS)

    Herguedas, Beatriz; Martínez-Júlvez, Marta; Frago, Susana; Medina, Milagros; Hermoso, Juan A.

    2009-01-01

    Native and selenomethionine-labelled FAD synthetase from C. ammoniagenes have been crystallized by the hanging-drop vapour-diffusion method. A MAD data set for SeMet-labelled FAD synthetase was collected to 2.42 Å resolution, while data sets were collected to 1.95 Å resolution for the native crystals. FAD synthetase from Corynebacterium ammoniagenes (CaFADS), a prokaryotic bifunctional enzyme that catalyses the phosphorylation of riboflavin as well as the adenylylation of FMN, has been crystallized using the hanging-drop vapour-diffusion method at 277 K. Diffraction-quality cubic crystals of native and selenomethionine-labelled (SeMet-CaFADS) protein belonged to the cubic space group P2 1 3, with unit-cell parameters a = b = c = 133.47 Å and a = b = c = 133.40 Å, respectively. Data sets for native and SeMet-containing crystals were collected to 1.95 and 2.42 Å resolution, respectively

  16. Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.

    Science.gov (United States)

    Tossounian, Maria-Armineh; Pedre, Brandán; Wahni, Khadija; Erdogan, Huriye; Vertommen, Didier; Van Molle, Inge; Messens, Joris

    2015-05-01

    Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Mastitis in dairy cattle caused by Corynebacterium pseudotuberculosis and the feasibility of transmission by houseflies. I.

    Science.gov (United States)

    Yeruham, I; Braverman, Y; Shpigel, N Y; Chizov-Ginzburg, A; Saran, A; Winkler, M

    1996-09-01

    Morbidity due to Corynebacterium pseudotuberculosis infection occurred in 29 dairy herds. The disease appeared basically in three clinical forms: cutaneous, mastitic, and visceral. The appearance of the disease showed a marked seasonality: in 23 herds it occurred during the spring and summer months (dry season) (March-October). The mastitic form occurred in only 10 herds and the causative bacterium was isolated from 33 cows (5.8%). All the strains of C. pseudotuberculosis isolated from the milk samples were found not to be nitrate reducers. The bacterium was excreted in the milk of six cows from herd B during a period of 11 months. In the mastitic cows, a decrease in milk production and considerable increases in the somatic cell count were noted. C. pseudotuberculosis was isolated from houseflies collected over a cow lesion. Laboratory-reared houseflies were successfully infected with C. pseudotuberculosis-contaminated milk, broth and sugar cubes. Flies infected with the bacterium from contaminated milk excreted the bacterium in their droppings for up to 4 h and from their saliva for up to 3 h post infection. The bacterium survived on the external organs of houseflies for no longer than 10 min post infection, after the flies had been dipped in contaminated broth.

  18. Carrier state of Haemophilus influenzae type b (Hib, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara, Nepal

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    Dharm Raj Bhatta

    2014-02-01

    Full Text Available Objective: To determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children. Methods: Specimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 1 02 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures. Results: Potential pathogens isolated in our study were S. pneumoniae (14.7%, Staphylococcus aureus (12.7%, Corynebacterium diphtheriae (3.9%, Streptococcus pyogenes (3.9% and Haemophilus influenzae (1.9%. Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73% and resistance of Staphylococcus aureus to oxacillin (23%. Conclusions: Pharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.

  19. Cystic Neutrophilic Granulomatous Mastitis: Further Characterization of a Distinctive Histopathologic Entity Not Always Demonstrably Attributable to Corynebacterium Infection.

    Science.gov (United States)

    D'Alfonso, Timothy M; Moo, Tracy-Ann; Arleo, Elizabeth K; Cheng, Esther; Antonio, Lilian B; Hoda, Syed A

    2015-10-01

    Granulomatous lobular mastitis (GLM) is an uncommon condition that typically occurs in parous, reproductive-aged women and can simulate malignancy on the basis of clinical and imaging features. A distinctive histologic pattern termed cystic neutrophilic granulomatous mastitis (CNGM) is seen in some cases of GLM and has been associated with Corynebacterium infection. We sought to further characterize the clinical, imaging, and histopathologic features of CNGM by studying 12 cases and attempted to establish the relationship of this disease with Corynebacterium infection. Patients were women ranging in age from 25 to 49 years (median: 34 y), and all presented with a palpable mass that was painful in half of the cases. In 2 of 9 cases, imaging was highly suspicious for malignancy (BI-RADS 5). CNGM was characterized by lobulocentric granulomas with mixed inflammation and clear vacuoles lined by neutrophils within granulomas. Gram-positive bacilli were identified in 5/12 cases. In 4 patients, the disease process worsened after the diagnostic core biopsy, with the development of a draining sinus in 2 cases. No growth of bacteria was seen in any microbial cultures. No bacterial DNA was identified by 16S rDNA polymerase chain reaction for 1 case that showed gram-positive bacilli on histology. Patients were treated with variable combinations of surgery, antibiotics, and steroids. The time to significant resolution of symptoms ranged from 2 weeks to 6 months. Similar to other forms of GLM, CNGM can mimic malignancy clinically and on imaging. When encountered in a needle core biopsy sample, recognition of the characteristic histologic pattern and its possible association with Corynebacterium infection can help guide treatment.

  20. The Druggable Pocketome of Corynebacterium diphtheriae: A New Approach for in silico Putative Druggable Targets

    Science.gov (United States)

    Hassan, Syed S.; Jamal, Syed B.; Radusky, Leandro G.; Tiwari, Sandeep; Ullah, Asad; Ali, Javed; Behramand; de Carvalho, Paulo V. S. D.; Shams, Rida; Khan, Sabir; Figueiredo, Henrique C. P.; Barh, Debmalya; Ghosh, Preetam; Silva, Artur; Baumbach, Jan; Röttger, Richard; Turjanski, Adrián G.; Azevedo, Vasco A. C.

    2018-01-01

    Diphtheria is an acute and highly infectious disease, previously regarded as endemic in nature but vaccine-preventable, is caused by Corynebacterium diphtheriae (Cd). In this work, we used an in silico approach along the 13 complete genome sequences of C. diphtheriae followed by a computational assessment of structural information of the binding sites to characterize the “pocketome druggability.” To this end, we first computed the “modelome” (3D structures of a complete genome) of a randomly selected reference strain Cd NCTC13129; that had 13,763 open reading frames (ORFs) and resulted in 1,253 (∼9%) structure models. The amino acid sequences of these modeled structures were compared with the remaining 12 genomes and consequently, 438 conserved protein sequences were obtained. The RCSB-PDB database was consulted to check the template structures for these conserved proteins and as a result, 401 adequate 3D models were obtained. We subsequently predicted the protein pockets for the obtained set of models and kept only the conserved pockets that had highly druggable (HD) values (137 across all strains). Later, an off-target host homology analyses was performed considering the human proteome using NCBI database. Furthermore, the gene essentiality analysis was carried out that gave a final set of 10-conserved targets possessing highly druggable protein pockets. To check the target identification robustness of the pipeline used in this work, we crosschecked the final target list with another in-house target identification approach for C. diphtheriae thereby obtaining three common targets, these were; hisE-phosphoribosyl-ATP pyrophosphatase, glpX-fructose 1,6-bisphosphatase II, and rpsH-30S ribosomal protein S8. Our predicted results suggest that the in silico approach used could potentially aid in experimental polypharmacological target determination in C. diphtheriae and other pathogens, thereby, might complement the existing and new drug-discovery pipelines

  1. Technetium-99m labeling and fibronectin binding ability of Corynebacterium diphtheriae

    International Nuclear Information System (INIS)

    Souza, S.M.S.; Nagao, P.E.; Bernardo-Filho, M.; Pereira, G.A.; Napoleao, F.; Andrade, A.F.B.; Hirata Junior, R.; Mattos-Guaraldi, A.L.

    2004-01-01

    The use of radionuclides has permitted advances in areas of clinical and scientific knowledge. Several molecules and cells have been labelled with Technetium-99m ( 99m Tc). The stannous chloride (SnCl 2 ) has a significant influence on the labeling and stability of 99m Tc radiotracers. The frequent risk of diphtheria epidemics has intensified interest in the virulence factors of Corynebacterium diphtheriae. Although studies have looked at potential adhesins including haemagglutinins and exposed sugar residues, the molecular basis of mechanisms of adherence remains unclear. Adherence of pathogens to mammalian tissues may be mediated by fibronectin (FN) found in body fluids, matrix of connective tissues, and cell surfaces. In the present study we evaluated the binding ability to human plasma FN by 99m Tc labeled-C.diphtheriae. Due to adverse effects of stannous ions, microorganisms were submitted to survival and filamentation induction assays. Data showed a dose dependent susceptibility to SnCl 2 bactericidal effects. Cell filamentation was observed for concentrations of SnCl 2 > 110 μg/ml. Adherence levels of 99m Tc labelled 241strain to coverslips coated with 20 μg/ml FN were higher (P = 0.0037) than coated with bovine serum albumin. FN binding by the sucrose fermenting 241 C. diphtheriae strain (8.9% + 2.6) was significantly lower (P=0.0139) than Staphylococcus aureus Cowan I strain (34.1% ± 1.2). Therefore, bacterial 99m Tc labeling represents an additional tool that may contribute to the comprehension of C. diphtheriae interactions with host receptors such as FN that act as biological organizers by holding bacterial cells in position and guiding their migration. (author)

  2. Surveillance of a Ventilated Rack System for Corynebacterium bovis by Sampling Exhaust-Air Manifolds.

    Science.gov (United States)

    Manuel, Christopher A; Pugazhenthi, Umarani; Leszczynski, Jori K

    2016-01-01

    Corynebacterium bovis causes an opportunistic infection of nude (Foxn1, nu/nu) mice, leading to nude mouse hyperkeratotic dermatitis (scaly skin disease). Enzootic in many nude mouse colonies, C. bovis spreads rapidly to naive nude mice, despite modern husbandry practices, and is very difficult to eradicate. To facilitate rapid detection in support of eradication efforts, we investigated a surveillance method based on quantitative real-time PCR (qPCR) evaluation of swabs collected from the horizontal exhaust manifold (HEM) of an IVC rack system. We first evaluated the efficacy of rack sanitation methods for removing C. bovis DNA from the HEM of racks housing endemic colonies of infected nude mice. Pressurized water used to flush the racks' air exhaust system followed by a standard rack-washer cycle was ineffective in eliminating C. bovis DNA. Only after autoclaving did all sanitized racks test negative for C. bovis DNA. We then measured the effects of stage of infection (early or established), cage density, and cage location on the rack on time-to-detection at the HEM. Stage of infection significantly affected time-to-detection, independent of cage location. Early infections required 7.3 ± 1.2 d whereas established infections required 1 ± 0 d for detection of C. bovis at the HEM. Cage density influenced the quantity of C. bovis DNA detected but not time-to-detection. The location of the cage on the rack affected the time-to-detection only during early C. bovis infections. We suggest that qPCR swabs of HEM are useful during the routine surveillance of nude mouse colonies for C. bovis infection.

  3. An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae.

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    Syed Babar Jamal

    Full Text Available Corynebacterium diphtheriae (Cd is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However, numerous drug-resistant strains emerged recently that consequently decreased the efficacy of current therapeutics and vaccines, thereby obliging the scientific community to start investigating new therapeutic targets in pathogenic microorganisms. In this study, our contributions include the prediction of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23 proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983 were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives. The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae putative proteins for broad-spectrum development of novel drugs and vaccines, owing to the fact that some of these targets have already been identified and validated in other organisms.

  4. Implantation of Corynebacterium pseudodiphtheriticum for elimination of Staphylococcus aureus from the nasal cavity in volunteers

    Science.gov (United States)

    Viacheslav, Ilyin; Kiryukhina, Nataliya

    Nasal carriage of Staphylococcus aureus is a well-documented risk factor of infection and inflammation of the skin, soft tissues and bacteremia. It is also known that most often etiology of these disorders is associated with autoinfection. The present-day methods of opportunistic pathogens eradication from the nasal cavity are based principally on the use of antiseptic and antibacterial agents. For instance, a local antibiotic mupirocin in the form of nasal ointment is considered to be the gold standard for the treatment of S. aureus carriage. The literature describes investigations showing how mupirocin can strengthen antibiotic resistance in S. aureus strains, including those with methicillin resistance (MRSA). It is also common knowledge that recolonization of the nasal mucous membrane takes place within several months after mupirocin treatment. This circumstance dictates the necessity to look for alternative ways of preventing the S. aureus carriage and methods of elimination. One of the methods of nasal S. aureus elimination is implantation of nonpathogenic microorganisms which will extrude opportunistic pathogens without impinging the symbiotic microbiota. Effectiveness of saline suspension of Corynebacterium pseudodiphtheriticum containing spray was assessed in a several chamber experiments with simulation of some spaceflight factors (dry immersion, isolation). Various schemes of application of preparations were applied. In all cases of corynebacteria application the strong inhibiting effect against S. aureus was detected. This fact opens a prospect of using nonpathogenic corynebacteria as a nasal probiotic. Administration of the nasal corynebacteria spray possibly prevented cross-infection by MRSA and appearance of staphylococcal infection. Further pre-clinical and clinical study of this bacterial therapy method is under development.

  5. Complete genome sequence and lifestyle of black-pigmented Corynebacterium aurimucosum ATCC 700975 (formerly C. nigricans CN-1 isolated from a vaginal swab of a woman with spontaneous abortion

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    Gartemann Karl-Heinz

    2010-02-01

    Full Text Available Abstract Background Corynebacterium aurimucosum is a slightly yellowish, non-lipophilic, facultative anaerobic member of the genus Corynebacterium and predominantly isolated from human clinical specimens. Unusual black-pigmented variants of C. aurimucosum (originally named as C. nigricans continue to be recovered from the female urogenital tract and they are associated with complications during pregnancy. C. aurimucosum ATCC 700975 (C. nigricans CN-1 was originally isolated from a vaginal swab of a 34-year-old woman who experienced a spontaneous abortion during month six of pregnancy. For a better understanding of the physiology and lifestyle of this potential urogenital pathogen, the complete genome sequence of C. aurimucosum ATCC 700975 was determined. Results Sequencing and assembly of the C. aurimucosum ATCC 700975 genome yielded a circular chromosome of 2,790,189 bp in size and the 29,037-bp plasmid pET44827. Specific gene sets associated with the central metabolism of C. aurimucosum apparently provide enhanced metabolic flexibility and adaptability in aerobic, anaerobic and low-pH environments, including gene clusters for the uptake and degradation of aromatic amines, L-histidine and L-tartrate as well as a gene region for the formation of selenocysteine and its incorporation into formate dehydrogenase. Plasmid pET44827 codes for a non-ribosomal peptide synthetase that plays the pivotal role in the synthesis of the characteristic black pigment of C. aurimucosum ATCC 700975. Conclusions The data obtained by the genome project suggest that C. aurimucosum could be both a resident of the human gut and possibly a pathogen in the female genital tract causing complications during pregnancy. Since hitherto all black-pigmented C. aurimucosum strains have been recovered from female genital source, biosynthesis of the pigment is apparently required for colonization by protecting the bacterial cells against the high hydrogen peroxide concentration in

  6. Identification of clinically relevant Corynebacterium strains by Api Coryne, MALDI-TOF-mass spectrometry and molecular approaches.

    Science.gov (United States)

    Alibi, S; Ferjani, A; Gaillot, O; Marzouk, M; Courcol, R; Boukadida, J

    2015-09-01

    We evaluated the Bruker Biotyper matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) for the identification of 97 Corynebacterium clinical in comparison to identification strains by Api Coryne and MALDI-TOF-MS using 16S rRNA gene and hypervariable region of rpoB genes sequencing as a reference method. C. striatum was the predominant species isolated followed by C. amycolatum. There was an agreement between Api Coryne strips and MALDI-TOF-MS identification in 88.65% of cases. MALDI-TOF-MS was unable to differentiate C. aurimucosum from C. minutissimum and C. minutissimum from C. singulare but reliably identify 92 of 97 (94.84%) strains. Two strains remained incompletely identified to the species level by MALDI-TOF-MS and molecular approaches. They belonged to Cellulomonas and Pseudoclavibacter genus. In conclusion, MALDI-TOF-MS is a rapid and reliable method for the identification of Corynebacterium species. However, some limits have been noted and have to be resolved by the application of molecular methods. Copyright © 2015. Published by Elsevier SAS.

  7. Corynebacterium fournierii,’ a new bacterial species isolated from the vaginal sample of a patient with bacterial vaginosis

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    K. Diop

    2017-07-01

    Full Text Available Here we describe briefly ‘Corynebacterium fournierii’ strain Marseille P2948 (= CSUR P2948 = DSM103271, a new bacterium that was isolated from the vaginal sample of a 21-year-old woman with bacterial vaginosis.

  8. The pan-genome of the animal pathogen Corynebacterium pseudotuberculosis reveals differences in genome plasticity between the biovar ovis and equi strains

    DEFF Research Database (Denmark)

    Soares, Siomar C; Silva, Artur; Trost, Eva

    2013-01-01

    , Corynebacterium pseudotuberculosis infections pose a rising worldwide economic problem in ruminants. The complete genome sequences of 15 C. pseudotuberculosis strains isolated from different hosts and countries were comparatively analyzed using a pan-genomic strategy. Phylogenomic, pan-genomic, core genomic...

  9. Multiplex polymerase chain reaction to identify and determine the toxigenicity of Corynebacterium spp with zoonotic potential and an overview of human and animal infections

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    Luciene de Fátima Costa Torres

    2013-05-01

    Full Text Available Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis constitute a group of potentially toxigenic microorganisms that are related to different infectious processes in animal and human hosts. Currently, there is a lack of information on the prevalence of disease caused by these pathogens, which is partially due to a reduction in the frequency of routine laboratory testing. In this study, a multiplex polymerase chain reaction (mPCR assay that can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential was developed. This assay uses five primer pairs targeting the following genes: rpoB (Corynebacterium spp, 16S rRNA (C. ulcerans and C. pseudotuberculosis, pld (C. pseudotuberculosis, dtxR (C. diphtheriae and tox [diphtheria toxin (DT ]. In addition to describing this assay, we review the literature regarding the diseases caused by these pathogens. Of the 213 coryneform strains tested, the mPCR results for all toxigenic and non-toxigenic strains of C . diphtheriae, C. ulcerans and C. pseudotuberculosis were in 100% agreement with the results of standard biochemical tests and PCR-DT. As an alternative to conventional methods, due to its advantages of specificity and speed, the mPCR assay used in this study may successfully be applied for the diagnosis of human and/or animal diseases caused by potentially toxigenic corynebacterial species.

  10. Prediction of DtxR regulon: Identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae

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    Hasnain Seyed

    2004-09-01

    Full Text Available Abstract Background The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae. Result Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG, an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin. Conclusions We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a molecular link between Fe+2-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2 and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase

  11. A comparative study on phyllosphere nitrogen fixation by newly isolated Corynebacterium sp. & Flavobacterium sp. and their potentialities as biofertilizer.

    Science.gov (United States)

    Giri, S; Pati, B R

    2004-01-01

    A number of nitrogen fixing bacteria has been isolated from forest phyllosphere on the basis of nitrogenase activity. Among them two best isolates are selected and identified as Corynebacterium sp. AN1 & Flavobacterium sp. TK2 able to reduce 88 and 132 n mol of acetylene (10(8)cells(-1)h(-1)) respectively. They were grown in large amount and sprayed on the phyllosphere of maize plants as a substitute for nitrogenous fertilizer. Marked improvements in growth and total nitrogen content of the plant have been observed by the application of these nitrogen-fixing bacteria. An average 30-37% increase in yield was obtained, which is nearer to chemical fertilizer treatment. Comparatively better effect was obtained by application of Flavobacterium sp.

  12. Comprehensive update of dalbavancin activity when tested against uncommonly isolated streptococci, Corynebacterium spp., Listeria monocytogenes, and Micrococcus spp. (1357 strains).

    Science.gov (United States)

    Jones, Ronald N; Stilwell, Matthew G

    2013-06-01

    Dalbavancin is an investigational lipoglycopeptide having an extended serum elimination half-life allowing once-weekly dosing. Data from testing 1357 strains of uncommonly isolated species expand the dalbavancin spectrum details as follows (MIC50/90): β-haemolytic streptococcal serogroups C, F, and G (≤0.03/≤0.03 μg/mL), 7 viridans group of streptococci (≤0.03/≤0.03-0.06 μg/mL), 5 Corynebacterium spp. (0.06/0.12 μg/mL), Listeria monocytogenes (0.06/0.12 μg/mL), and Micrococcus spp. (≤0.03/≤0.03 μg/mL). Among all reported isolates, 99.8% of tested strains were inhibited at dalbavancin MIC values at ≤0.12 μg/mL. Dalbavancin remains very potent against rarer Gram-positive pathogens, using in vitro test experience with organisms cultured through 2011. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Novel Polyoxyethylene-Containing Glycolipids Are Synthesized in Corynebacterium matruchotii and Mycobacterium smegmatis Cultured in the Presence of Tween 80

    Directory of Open Access Journals (Sweden)

    Cindy Wang

    2011-01-01

    Full Text Available The addition of polyoxyethylene sorbitan monooleate (Tween 80 to a culture of mycobacteria greatly influences cell permeability and sensitivity to antibiotics but very little is known regarding the underlying mechanism. Here we show that Corynebacterium matruchotii (surrogate of mycobacteria converts Tween 80 to a structural series of polyoxyethylenic acids which are then used to form novel series-2A and series-2B glycolipids. Minor series-3 glycolipids were also synthesized. The polyoxyethylenic acids replaced corynomycolic acids in the cell wall. Correspondingly the trehalose dicorynomycolate content was reduced. MALDI mass spectrometry, MS-MS, 1H-NMR, and 13C-NMR were used to characterize the series-2 glycolipids. Series-2A glycolipid is trehalose 6-C36:2-corynomycolate-6′-polyoxyethylenate and series-2B glycolipid is trehalose 6-C36:2-corynomycolate-6′-furan ring-containing polyoxyethylenate. Mycobacterium smegmatis grown in the presence of Tween 80 also synthesizes series-2 type glycolipids. The synthesis of these novel glycolipids in corynebacteria and mycobacteria should result in gross changes in the cell wall permeability and drug sensitivity.

  14. Corynebacterium diphtheriae in a free-roaming red fox: case report and historical review on diphtheria in animals.

    Science.gov (United States)

    Sing, Andreas; Konrad, Regina; Meinel, Dominik M; Mauder, Norman; Schwabe, Ingo; Sting, Reinhard

    2016-08-01

    Corynebacterium diphtheriae, the classical causative agent of diphtheria, is considered to be nearly restricted to humans. Here we report the first finding of a non-toxigenic C. diphtheriae biovar belfanti strain in a free-roaming wild animal. The strain obtained from the subcutis and mammary gland of a dead red fox (Vulpes vulpes) was characterized by biochemical and molecular methods including MALDI-TOF and Multi Locus Sequence Typing. Since C. diphtheriae infections of animals, usually with close contact to humans, are reported only very rarely, an intense review comprising also scientific literature from the beginning of the 20th century was performed. Besides the present case, only 11 previously reported C. diphtheriae animal infections could be verified using current scientific criteria. Our report is the first on the isolation of C. diphtheriae from a wildlife animal without any previous human contact. In contrast, the very few unambiguous publications on C. diphtheriae in animals referred to livestock or pet animals with close human contact. C. diphtheriae carriage in animals has to be considered as an exceptionally rare event.

  15. Identification of membrane-associated proteins with pathogenic potential expressed by Corynebacterium pseudotuberculosis grown in animal serum.

    Science.gov (United States)

    Raynal, José Tadeu; Bastos, Bruno Lopes; Vilas-Boas, Priscilla Carolinne Bagano; Sousa, Thiago de Jesus; Costa-Silva, Marcos; de Sá, Maria da Conceição Aquino; Portela, Ricardo Wagner; Moura-Costa, Lília Ferreira; Azevedo, Vasco; Meyer, Roberto

    2018-01-25

    Previous works defining antigens that might be used as vaccine targets against Corynebacterium pseudotuberculosis, which is the causative agent of sheep and goat caseous lymphadenitis, have focused on secreted proteins produced in a chemically defined culture media. Considering that such antigens might not reflect the repertoire of proteins expressed during infection conditions, this experiment aimed to investigate the membrane-associated proteins with pathogenic potential expressed by C. pseudotuberculosis grown directly in animal serum. Its membrane-associated proteins have been extracted using an organic solvent enrichment methodology, followed by LC-MS/MS and bioinformatics analysis for protein identification and classification. The results revealed 22 membrane-associated proteins characterized as potentially pathogenic. An interaction network analysis indicated that the four potentially pathogenic proteins ciuA, fagA, OppA4 and OppCD were biologically connected within two distinct network pathways, which were both associated with the ABC Transporters KEGG pathway. These results suggest that C. pseudotuberculosis pathogenesis might be associated with the transport and uptake of nutrients; other seven identified potentially pathogenic membrane proteins also suggest that pathogenesis might involve events of bacterial resistance and adhesion. The proteins herein reported potentially reflect part of the protein repertoire expressed during real infection conditions and might be tested as vaccine antigens.

  16. Phenotypic, molecular characterization, antimicrobial susceptibility and draft genome sequence of Corynebacterium argentoratense strains isolated from clinical samples

    Directory of Open Access Journals (Sweden)

    I. Fernández-Natal

    2016-03-01

    Full Text Available During a 12-year period we isolated five Corynebacterium argentoratense strains identified by phenotypic methods, including the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF and 16S rRNA gene sequencing. In addition, antimicrobial susceptibility was determined, and genome sequencing for the detection of antibiotic resistance genes was performed. The organisms were isolated from blood and throat cultures and could be identified by all methods used. All strains were resistant to cotrimoxazole, and resistance to β-lactams was partly present. Two strains were resistant to erythromycin and clindamycin. The draft genome sequences of theses isolates revealed the presence of the erm(X resistance gene that is embedded in the genetic structure of the transposable element Tn5423. Although rarely reported as a human pathogen, C. argentoratense can be involved in bacteraemia and probably in other infections. Our results also show that horizontal transfer of genes responsible for antibiotic resistance is occurring in this species.

  17. Diphtheria in the Republic of Georgia: Use of Molecular Typing Techniques for Characterization of Corynebacterium diphtheriae Strains

    Science.gov (United States)

    Sulakvelidze, Alexander; Kekelidze, Merab; Gomelauri, Tsaro; Deng, Yingkang; Khetsuriani, Nino; Kobaidze, Ketino; De Zoysa, Aruni; Efstratiou, Androulla; Morris, J. Glenn; Imnadze, Paata

    1999-01-01

    Sixty-six Corynebacterium diphtheriae strains (62 of the gravis biotype and 4 of the mitis biotype) isolated during the Georgian diphtheria epidemic of 1993 to 1998 and 13 non-Georgian C. diphtheriae strains (10 Russian and 3 reference isolates) were characterized by (i) biotyping, (ii) toxigenicity testing with the Elek assay and PCR, (iii) the randomly amplified polymorphic DNA (RAPD) technique, and (iv) pulsed-field gel electrophoresis (PFGE). Fifteen selected strains were ribotyped. Six RAPD types and 15 PFGE patterns were identified among all strains examined, and 12 ribotypes were found among the 15 strains that were ribotyped. The Georgian epidemic apparently was caused by one major clonal group of C. diphtheriae (PFGE type A, ribotype R1), which was identical to the predominant epidemic strain(s) isolated during the concurrent diphtheria epidemic in Russia. A dendrogram based on the PFGE patterns revealed profound differences between the minor (nonpredominant) epidemic strains found in Georgia and Russia. The methodologies for RAPD typing, ribotyping, and PFGE typing of C. diphtheriae strains were improved to enable rapid and convenient molecular typing of the strains. The RAPD technique was adequate for biotype differentiation; however, PFGE and ribotyping were better (and equal to each other) at discriminating between epidemiologically related and unrelated isolates. PMID:10488190

  18. Expression, purification, crystallization and preliminary crystallographic analysis of SpaA, a major pilin from Corynebacterium diphtheriae

    International Nuclear Information System (INIS)

    Kang, Hae Joo; Paterson, Neil G.; Baker, Edward N.

    2009-01-01

    SpaA, one of the major pilins of C. diphtheriae, has been expressed, purified and crystallized and X-ray diffraction data have been collected to 1.6 Å resolution. Bacterial pili are cell-surface organelles that are critically involved in adhesion to host cells, leading to the colonization of host tissues and the establishment of infections. Whereas the pili of Gram-negative bacteria have been extensively studied, those of Gram-positive bacteria came to light only recently after the discovery and characterization of Corynebacterium diphtheriae pili. These newly discovered pili are formed by the covalent polymerization of pilin subunits catalyzed by sortase enzymes, making them fundamentally different from the noncovalent pilin assemblies of Gram-negative bacteria. Here, the expression, crystallization and preliminary crystallographic analysis of SpaA, which forms the shaft of one of the three types of pili expressed by C. diphtheriae, are reported. SpaA 53–486 crystals diffracted to 1.6 Å resolution and belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 34.9, b = 64.1, c = 198.7 Å, α = β = γ = 90°

  19. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  20. Technetium-99m labeling and fibronectin binding ability of Corynebacterium diphtheriae; Marcacao de Corynebacterium diphtheriae com Tecnecio-99m e avaliacao da capacidade de ligacao a fibronectina de plasma humano

    Energy Technology Data Exchange (ETDEWEB)

    Souza, S.M.S.; Nagao, P.E.; Bernardo-Filho, M. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes; Pereira, G.A.; Napoleao, F.; Andrade, A.F.B.; Hirata Junior, R.; Mattos-Guaraldi, A.L. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas

    2004-04-15

    The use of radionuclides has permitted advances in areas of clinical and scientific knowledge. Several molecules and cells have been labelled with Technetium-99m ({sup 99m}Tc). The stannous chloride (SnCl{sub 2}) has a significant influence on the labeling and stability of {sup 99m}Tc radiotracers. The frequent risk of diphtheria epidemics has intensified interest in the virulence factors of Corynebacterium diphtheriae. Although studies have looked at potential adhesins including haemagglutinins and exposed sugar residues, the molecular basis of mechanisms of adherence remains unclear. Adherence of pathogens to mammalian tissues may be mediated by fibronectin (FN) found in body fluids, matrix of connective tissues, and cell surfaces. In the present study we evaluated the binding ability to human plasma FN by {sup 99m}Tc labeled-C.diphtheriae. Due to adverse effects of stannous ions, microorganisms were submitted to survival and filamentation induction assays. Data showed a dose dependent susceptibility to SnCl{sub 2} bactericidal effects. Cell filamentation was observed for concentrations of SnCl{sub 2} > 110 {mu}g/ml. Adherence levels of {sup 99m}Tc labelled 241strain to coverslips coated with 20 {mu}g/ml FN were higher (P = 0.0037) than coated with bovine serum albumin. FN binding by the sucrose fermenting 241 C. diphtheriae strain (8.9% + 2.6) was significantly lower (P=0.0139) than Staphylococcus aureus Cowan I strain (34.1% {+-} 1.2). Therefore, bacterial {sup 99m}Tc labeling represents an additional tool that may contribute to the comprehension of C. diphtheriae interactions with host receptors such as FN that act as biological organizers by holding bacterial cells in position and guiding their migration. (author)

  1. [Corynebacterium imitans isolated from blood culture in a patient with suspected bacteremia - the first isolation from human clinical material in the Czech Republic].

    Science.gov (United States)

    JeŽek, Petr; Zavadilová, Jana; Kolínská, Renáta; Švec, Pavel; Guttwirth, Jiří; Petráš, Petr

    2014-09-01

    The current view of the clinical importance of nondiphtherial corynebacteria recovered from human clinical material has changed considerably in recent decades; in many cases, a direct etiological role is assumed or has already been demonstrated. Presented is a case of suspected bacteremia in a hospitalized elderly woman with isolation of the very rare species Corynebacterium imitans from blood culture. However, the etiological significance of the isolated microorganism remains unclear. The aim was not to demonstrate the etiological significance of the isolated C. imitans strain but to report the occurrence of this very rare species which is considered to be the first isolation from humans in the Czech Republic.

  2. Bioconversion of Gibberellin Fermentation Residue into Feed Supplement and Organic Fertilizer Employing Housefly (Musca domestica L. Assisted by Corynebacterium variabile.

    Directory of Open Access Journals (Sweden)

    Sen Yang

    Full Text Available The accumulation of a considerable quantity of gibberellin fermentation residue (GFR during gibberellic acid A3 (GA3 production not only results in the waste of many resources, but also poses a potential hazard to the environment, indicating that the safe treatment of GFR has become an urgent issue for GA3 industry. The key to recycle GFR is converting it into an available resource and removing the GA3 residue. To this end, we established a co-bioconversion process in this study using house fly larvae (HFL and microbes (Corynebacterium variabile to convert GFR into insect biomass and organic fertilizer. About 85.5% GA3 in the GFR was removed under the following optimized solid-state fermentation conditions: 60% GFR, 40% rice straw powder, pH 8.5 and 6 days at 26 °C. A total of 371 g housefly larvae meal and 2,064 g digested residue were bio-converted from 3,500 g raw GFR mixture contaning1, 400 g rice straw in the unit of (calculated dry matter. HFL meal derived from GFR contained 56.4% protein, 21.6% fat, and several essential amino acids, suggesting that it is a potential alternative animal feed protein source. Additionally, the digested GFR could be utilized as an organic fertilizer with a content of 3.2% total nitrogen, 2.0% inorganic phosphorus, 1.3% potassium and 91.5% organic matter. This novel GFR bio-conversion method can mitigate potential environmental pollution and recycle the waste resources.

  3. Bioconversion of Gibberellin Fermentation Residue into Feed Supplement and Organic Fertilizer Employing Housefly (Musca domestica L.) Assisted by Corynebacterium variabile

    Science.gov (United States)

    Yang, Sen; Xie, Jiufeng; Hu, Nan; Liu, Yixiong; Zhang, Jiner; Ye, Xiaobin; Liu, Ziduo

    2015-01-01

    The accumulation of a considerable quantity of gibberellin fermentation residue (GFR) during gibberellic acid A3 (GA3) production not only results in the waste of many resources, but also poses a potential hazard to the environment, indicating that the safe treatment of GFR has become an urgent issue for GA3 industry. The key to recycle GFR is converting it into an available resource and removing the GA3 residue. To this end, we established a co-bioconversion process in this study using house fly larvae (HFL) and microbes (Corynebacterium variabile) to convert GFR into insect biomass and organic fertilizer. About 85.5% GA3 in the GFR was removed under the following optimized solid-state fermentation conditions: 60% GFR, 40% rice straw powder, pH 8.5 and 6 days at 26°C. A total of 371g housefly larvae meal and 2,064g digested residue were bio-converted from 3,500g raw GFR mixture contaning1, 400g rice straw in the unit of (calculated) dry matter. HFL meal derived from GFR contained 56.4% protein, 21.6% fat, and several essential amino acids, suggesting that it is a potential alternative animal feed protein source. Additionally, the digested GFR could be utilized as an organic fertilizer with a content of 3.2% total nitrogen, 2.0% inorganic phosphorus, 1.3% potassium and 91.5% organic matter. This novel GFR bio-conversion method can mitigate potential environmental pollution and recycle the waste resources. PMID:25992605

  4. Assessment of heavy metal tolerance and hexavalent chromium reducing potential of Corynebacterium paurometabolum SKPD 1204 isolated from chromite mine seepage

    Directory of Open Access Journals (Sweden)

    Amal Kanti Paul

    2016-07-01

    Full Text Available Corynebacterium paurometabolum SKPD 1204 (MTCC 8730, a heavy metal tolerant and chromate reducing bacterium isolated from chromite mine seepage of Odisha, India has been evaluated for chromate reduction under batch culture. The isolate was found to tolerate metals like Co(II, Cu(II, Ni(II, Mn(II, Zn(II, Fe(III and Hg(II along with Cr(VI and was resistant to different antibiotics as evaluated by disc-diffusion method. The isolate, SKPD 1204 was found to reduce 62.5% of 2 mM Cr(VI in Vogel Bonner broth within 8 days of incubation. Chromate reduction capability of SKPD 1204 decreased with increase in Cr(VI concentration, but increased with increase in cell density and attained its maximum at 1010 cells/mL. Chromate reducing efficiency of SKPD 1204 was promoted in the presence of glycerol and glucose, while the highest reduction was recorded at pH 7.0 and 35 °C. The reduction process was inhibited by divalent cations Zn(II, Cd(II, Cu(II, and Ni(II, but not by Mn(II. Anions like nitrate, phosphate, sulphate and sulphite was found to be inhibitory to the process of Cr(VI reduction. Similarly, sodium fluoride, carbonyl cyanide m-chlorophenylhydrazone, sodium azide and N, N,-Di cyclohexyl carboiimide were inhibitory to chromate reduction, while 2,4-dinitrophenol appeared to be neither promotive nor inhibitory to the process.

  5. AVALIAÇÃO DE FONTES DE CARBONO PARA A PRODUÇÃO DE INIBIDOR DE CRESCIMENTO DE Aspergillus fumigatus USP2 por Corynebacterium sp.

    Directory of Open Access Journals (Sweden)

    Gabrielle Fernanda Zimmer

    2013-07-01

    Full Text Available O aumento significativo na incidência de infecções fúngicas invasivas e a resistência natural de agentes etiológicos a antifúngicos existentes têm motivado a constante pesquisa por novos agentes antifúngicos nos ultimos anos. Neste sentido, foi selcionada uma cepa de Corynebacterium sp. com potencial antagonista frente à Aspergilus fumigatus USP2. A cepa foi cultivada em fase submersa e em fase sólida, avaliando-se a variação das fontes de glicose, sacarose e glicerol em presença de peptona, bem como o meio sintético Czapek. Os caldos de cultivo submerso foram utilizados para o ensaio de antagonismo microbiano com o fungo Aspergillus fumigatus USP2. Os resultados apontam que o cultivo em fase sólida utilizando glicose como fonte de carbono apresenta maior potencial inibitório da cepa de Corynebacterium sp. sobre o fungo Aspergillus fumigatus USP2.

  6. Characterization and antimicrobial susceptibility of one antibiotic-sensitive and one multidrug-resistant Corynebacterium kroppenstedtii strain isolated from patients with granulomatous mastitis

    Directory of Open Access Journals (Sweden)

    I. Fernández-Natal

    2016-11-01

    Full Text Available Human infections associated with Corynebacterium kroppenstedtii are rarely reported, and this organism is usually described as antibiotic sensitive. Almost all published cases of C. kroppenstedtii infections have been associated with breast pathology in women and have been described in New Zealand, France, Canada, India and Japan. Here we describe the microbiologic characteristics of two strains isolated from two women diagnosed of granulomatous mastitis in Spain. One C. kroppenstedtii isolate was antibiotic sensitive while the other was multidrug resistant. Biochemical identification was possible using a wide battery of methods including API Coryne V2.0, API Strep, API NH, API NE, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene amplification and sequencing. Antimicrobial susceptibility to 28 antibiotics as determined by Etest showed one isolate being sensitive to benzylpenicillin, ciprofloxacin, moxifloxacin, gentamicin, vancomycin, clindamycin, tetracycline, linezolid and rifampin. The second isolate showed resistance to ciprofloxacin, moxifloxacin, clindamycin, tetracycline and rifampin. The multidrug-resistant isolate contained the erm(X, tet(W, cmx, aphA1-IAB, strAB and sul1 resistance genes known from the R plasmid pJA144188 of Corynebacterium resistens. These genes were absent in the genome of the antibiotic-sensitive isolate. This report confirms the tropism of this microorganism for women's breasts and presents the first description of a multidrug-resistant C. kroppenstedtii strain.

  7. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  8. [Metabolic acidosis].

    Science.gov (United States)

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  9. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  10. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  11. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  12. Animal metabolism

    International Nuclear Information System (INIS)

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  13. Biotin-independent strains of Escherichia coli for enhanced streptavidin production.

    Science.gov (United States)

    Jeschek, Markus; Bahls, Maximilian O; Schneider, Veronika; Marlière, Philippe; Ward, Thomas R; Panke, Sven

    2017-03-01

    Biotin is an archetypal vitamin used as cofactor for carboxylation reactions found in all forms of life. However, biotin biosynthesis is an elaborate multi-enzymatic process and metabolically costly. Moreover, many industrially relevant organisms are incapable of biotin synthesis resulting in the requirement to supplement defined media. Here we describe the creation of biotin-independent strains of Escherichia coli and Corynebacterium glutamicum through installation of an optimized malonyl-CoA bypass, which re-routes natural fatty acid synthesis, rendering the previously essential vitamin completely obsolete. We utilize biotin-independent E. coli for the production of the high-value protein streptavidin which was hitherto restricted because of toxic effects due to biotin depletion. The engineered strain revealed significantly improved streptavidin production resulting in the highest titers and productivities reported for this protein to date. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  14. The uptake, distribution and translocation of 86Rb in alfalfa plants susceptible and resistant to the bacterial wilt and the effect of Corynebacterium insidiosum upon these processes

    International Nuclear Information System (INIS)

    Hanker, I.; Kudelova, A.

    1981-01-01

    Alfalfa (Medicago sativa L.) plants susceptible (S) and resistant (R) to bacterial wilt were fed via roots with a nutrient solution labelled with 86 Rb + , at different times after inoculation with Corynebacterium insidiosum (McCull.) H.L. Jens. The infection did not affect 86 Rb + uptake per plant in the course of a 14-day-period following inoculation; however, it affected its distribution differently in the S- and the R-plants. 86 Rb + uptake significantly decreased due to the infection in the S-plants on the day 49 after inoculation (a 4-h-exposure to 86 Rb + ), with the ions more slowly translocated to the shoots in diseased S-plants than in diseased R-plants. Likely factors causing these effects and their relationship to alfalfa resistance to bacterial wilt are discussed. (author)

  15. Isolation of Corynebacterium Xerosis from Jordanian Soil and a Study on its Antimicrobial Activity against a Range of Bacteria and Fungi

    International Nuclear Information System (INIS)

    El-Banna, Nasser

    2004-01-01

    A bacterial strain which has been identified as Corneybacterium Xerosis NB-2 was isolated from a soil sample from Jerash Private University, Jerash, Jordan. This isolate was found to produce an antimicrobial substance active only against filamentous fungi and yeasts (Aspergillus niger SQ 40, Fusarium oxysporium SQ11, Verticillium dahliae SQ 42, Saccharomyces SQ 46 and Candida albicans SQ 47). However, all tested gram-positive bacteria and gram negative bacteria (Bacillus megaterium SQ5, Bacillus cereus SQ6, Staphylococcus aureus SQ9, Streptococcus pyogens SQ10, Eschericshia coli SQ 22, Klepsiella spp SQ33 and SQ33 and Pseudonomas mallei SQ 34) were found to be resistant. In batch culture, the isolated NB-2 produced the antimicrobial substance late in the growth phase and antimicrobial activity of Corynebacterium Xerosis against filamentous fungi and yeasts which was not previously described. (author)

  16. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  17. in C. glutamicum ATCC 21799

    African Journals Online (AJOL)

    HP

    Rastegari et al. Trop J Pharm Res, ... Conclusion: A two-fold increase in lysine production was observed by cloning of the ASK gene in C. ..... Cambridge University Press 2006; Chapter 14: ... Cremer J, Eggeling L, Sahm H. Control of the lysine.

  18. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  19. Metabolic Surgery

    DEFF Research Database (Denmark)

    Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

    2018-01-01

    The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

  20. Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Ikinci

    2010-10-01

    Full Text Available Metabolic Syndrome is a combination of risk factors including common etiopathogenesis. These risk factors play different roles in occurence of atherosclerotic diseases, type 2 diabetes, and cancers. Although a compromise can not be achieved on differential diagnosis for MS, the existence of any three criterias enable to diagnose MS. These are abdominal obesity, dislipidemia (hypertrigliceridemia, hypercholesterolemia, and reduced high density lipoprotein hypertension, and elevated fasting blood glucose. According to the results of Metabolic Syndrome Research (METSAR, the overall prevalence of MS in Turkey is 34%; in females 40%, and in males it is 28%. As a result of “Western” diet, and increased frequency of obesity, MS is observed in children and in adolescents both in the world and in Turkey. Resulting in chronic diseases, it is thought that the syndrome can be prevented by healthy lifestyle behaviours. [TAF Prev Med Bull 2010; 9(5.000: 535-540

  1. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  2. Microbial Production of l-Serine from Renewable Feedstocks.

    Science.gov (United States)

    Zhang, Xiaomei; Xu, Guoqiang; Shi, Jinsong; Koffas, Mattheos A G; Xu, Zhenghong

    2018-07-01

    l-Serine is a non-essential amino acid that has wide and expanding applications in industry with a fast-growing market demand. Currently, extraction and enzymatic catalysis are the main processes for l-serine production. However, such approaches limit the industrial-scale applications of this important amino acid. Therefore, shifting to the direct fermentative production of l-serine from renewable feedstocks has attracted increasing attention. This review details the current status of microbial production of l-serine from renewable feedstocks. We also summarize the current trends in metabolic engineering strategies and techniques for the typical industrial organisms Corynebacterium glutamicum and Escherichia coli that have been developed to address and overcome major challenges in the l-serine production process. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. In vitro activities of the new semisynthetic glycopeptide telavancin (TD-6424), vancomycin, daptomycin, linezolid, and four comparator agents against anaerobic gram-positive species and Corynebacterium spp.

    Science.gov (United States)

    Goldstein, Ellie J C; Citron, Diane M; Merriam, C Vreni; Warren, Yumi A; Tyrrell, Kerin L; Fernandez, Helen T

    2004-06-01

    Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca(2+) to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC(90)s) for telavancin and vancomycin were as follows: Actinomyces spp. (n = 45), 0.25 and 1 microg/ml, respectively; Clostridium difficile (n = 14), 0.25 and 1 microg/ml, respectively; Clostridium ramosum (n = 16), 1 and 4 microg/ml, respectively; Clostridium innocuum (n = 15), 4 and 16 microg/ml, respectively; Clostridium clostridioforme (n = 15), 8 and 1 microg/ml, respectively; Eubacterium group (n = 33), 0.25 and 2 microg/ml, respectively; Lactobacillus spp. (n = 26), 0.5 and 4 microg/ml, respectively; Propionibacterium spp. (n = 34), 0.125 and 0.5 microg/ml, respectively; Peptostreptococcus spp. (n = 52), 0.125 and 0.5 microg/ml, respectively; and Corynebacterium spp. (n = 31), 0.03 and 0.5 microg/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three- to fivefold more active. Daptomycin had decreased activity (MIC > 4 microg/ml) against 14 strains of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 microg/ml) against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus spp. Imipenem and piperacillin

  4. [Construction of Corynebacterium crenatum AS 1.542 δ argR and analysis of transcriptional levels of the related genes of arginine biosynthetic pathway].

    Science.gov (United States)

    Chen, Xuelan; Tang, Li; Jiao, Haitao; Xu, Feng; Xiong, Yonghua

    2013-01-04

    ArgR, coded by the argR gene from Corynebacterium crenatum AS 1.542, acts as a negative regulator in arginine biosynthetic pathway. However, the effect of argR on transcriptional levels of the related biosynthetic genes has not been reported. Here, we constructed a deletion mutant of argR gene: C. crenatum AS 1.542 Delta argR using marker-less knockout technology, and compared the changes of transcriptional levels of the arginine biosynthetic genes between the mutant strain and the wild-type strain. We used marker-less knockout technology to construct C. crenatum AS 1.542 Delta argR and analyzed the changes of the relate genes at the transcriptional level using real-time fluorescence quantitative PCR. C. crenatum AS 1.542 Delta argR was successfully obtained and the transcriptional level of arginine biosynthetic genes in this mutant increased significantly with an average of about 162.1 folds. The arginine biosynthetic genes in C. crenatum are clearly controlled by the negative regulator ArgR. However, the deletion of this regulator does not result in a clear change in arginine production in the bacteria.

  5. Effect of biosurfactant and fertilizer on biodegradation of crude oil by marine isolates of Bacillus megaterium, Corynebacterium kutscheri and Pseudomonas aeruginosa.

    Science.gov (United States)

    Thavasi, Rengathavasi; Jayalakshmi, Singaram; Banat, Ibrahim M

    2011-01-01

    This study was conducted to investigate the effects of fertilizers and biosurfactants on biodegradation of crude oil by three marine bacterial isolates; Bacillus megaterium, Corynebacterium kutscheri and Pseudomonas aeruginosa. Five sets of experiments were carried out in shake flask and microcosm conditions with crude oil as follows: Set 1-only bacterial cells added (no fertilizer and biosurfactant), Set 2-with additional fertilizer only, Set 3-with additional biosurfactant only, Set 4-with added biosurfactant+fertilizer, Set 5-with no bacterial cells added (control), all the above experimental sets were incubated for 168 h. The biosurfactant+fertilizer added Set 4, resulted in maximum crude oil degradation within shake flask and microcosm conditions. Among the three bacterial isolates, P. aeruginosa and biosurfactant produced by this strain resulted in maximum crude oil degradation compared to the other two bacterial strains investigated. Interestingly, when biosurfactant and bacterial cells were used (Set 3), significant oil biodegradation activity occurred and the difference between this treatment and that in Set 4 with added fertilizer+biosurfactant were only 4-5% higher degradation level in shake flask and 3.2-7% in microcosm experiments for all three bacterial strains used. It is concluded that, biosurfactants alone capable of promoting biodegradation to a large extent without added fertilizers, which will reduce the cost of bioremediation process and minimizes the dilution or wash away problems encountered when water soluble fertilizers used during bioremediation of aquatic environments. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.

    Science.gov (United States)

    Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-12-01

    The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. © 2015 John Wiley & Sons Ltd.

  7. Selective oxidation of trimethylolpropane to 2,2-bis(hydroxymethyl)butyric acid using growing cells of Corynebacterium sp. ATCC 21245.

    Science.gov (United States)

    Sayed, Mahmoud; Dishisha, Tarek; Sayed, Waiel F; Salem, Wesam M; Temerk, Hanan A; Pyo, Sang-Hyun

    2016-03-10

    Multifunctional chemicals including hydroxycarboxylic acids are gaining increasing interest due to their growing applications in the polymer industry. One approach for their production is a biological selective oxidation of polyols, which is difficult to achieve by conventional chemical catalysis. In the present study, trimethylolpropane (TMP), a trihydric alcohol, was subjected to selective oxidation using growing cells of Corynebacterium sp. ATCC 21245 as a biocatalyst and yielding the dihydroxy-monocarboxylic acid, 2,2-bis(hydroxymethyl)butyric acid (BHMB). The study revealed that co-substrates are crucial for this reaction. Among the different evaluated co-substrates, a mixture of glucose, xylose and acetate at a ratio of 5:5:2 was found optimum. The optimal conditions for biotransformation were pH 8, 1v/v/m airflow and 500rpm stirring speed. In batch mode of operation, 70.6% of 5g/l TMP was converted to BHMB in 10 days. For recovery of the product the adsorption pattern of BHMB to the anion exchange resin, Ambersep(®) 900 (OH(-)), was investigated in batch and column experiments giving maximum static and dynamic binding capacities of 135 and 144mg/g resin, respectively. BHMB was separated with 89.7% of recovery yield from the fermentation broth. The approach is applicable for selective oxidation of other highly branched polyols by biotransformation. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Development of an indirect ELISA to detect Corynebacterium pseudotuberculosis specific antibodies in sheep employing T1 strain culture supernatant as antigen

    Directory of Open Access Journals (Sweden)

    Miriam F. Rebouças

    2013-11-01

    Full Text Available Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis (CLA, a chronic disease that affects goats and sheep, characterized by granuloma formation in subcutaneous and internal lymph nodes. CLA causes significant economic losses to commercial goat herds. In this study, we aimed to test secreted antigens secreted from T1 strain bacteria grown in brain heart infusion (BHI broth in an indirect ELISA system to determine the presence of specific immunoglobulins against C. pseudotuberculosis. We analyzed the BHI antigen electrophoretic profile and the recognition pattern by infected sheep sera samples. The ELISA results were compared with multiplex PCR assay and IFN-gamma production. The ELISA was able to discriminate between negative and positive animals, with a sensitivity of 89% and a specificity of 99%, using microbiological isolation as gold standard. When this assay was compared with multiplex PCR and specific IFN-gamma quantification, six discrepant results were found among thirty-two samples. We concluded that the ELISA using antigens secreted from C. pseudotuberculosis T1 strain growth in BHI broth culture can be used for the serodiagnosis of CLA in sheep.

  9. Conservación por congelación de Bordetella pertussis y Corynebacterium diphtheriae, empleados en la producción de vacunas para uso humano

    Directory of Open Access Journals (Sweden)

    Yilian Plasencia,

    2000-11-01

    Full Text Available En el presente estudio se evaluó el método de congelación a –70ºC para la preservación de Bordetella pertussis y Corynebacterium diphtheriae. Para verificar el sustento de los cultivos se realizó un adecuado control de calidad, que incluyó comprobación de pureza, viabilidad y estabilidad de las propiedades de interés. En este trabajo se probaron diferentes formulaciones. Se seleccionó la que arrojó los mejores resultados y se realizó un estudio de mantenimiento de las características evaluadas durante el tiempo. Para medir determinados parámetros se realizaron procesos a escala industrial, empleándose para esto un biorreactor Chemap de 35 L. Se tomaron como referencia los valores obtenidos por las cepas conservadas por liofilización. De esta forma se buscaron alternativas y soluciones a problemas presentados en su conservación. Los resultados obtenidos sugieren la posible inclusión en el Programa de Mantenimiento establecido.

  10. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

  11. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

  12. The obligate respiratory supercomplex from Actinobacteria.

    Science.gov (United States)

    Kao, Wei-Chun; Kleinschroth, Thomas; Nitschke, Wolfgang; Baymann, Frauke; Neehaul, Yashvin; Hellwig, Petra; Richers, Sebastian; Vonck, Janet; Bott, Michael; Hunte, Carola

    2016-10-01

    Actinobacteria are closely linked to human life as industrial producers of bioactive molecules and as human pathogens. Respiratory cytochrome bcc complex and cytochrome aa3 oxidase are key components of their aerobic energy metabolism. They form a supercomplex in the actinobacterial species Corynebacterium glutamicum. With comprehensive bioinformatics and phylogenetic analysis we show that genes for cyt bcc-aa3 supercomplex are characteristic for Actinobacteria (Actinobacteria and Acidimicrobiia, except the anaerobic orders Actinomycetales and Bifidobacteriales). An obligatory supercomplex is likely, due to the lack of genes encoding alternative electron transfer partners such as mono-heme cyt c. Instead, subunit QcrC of bcc complex, here classified as short di-heme cyt c, will provide the exclusive electron transfer link between the complexes as in C. glutamicum. Purified to high homogeneity, the C. glutamicum bcc-aa3 supercomplex contained all subunits and cofactors as analyzed by SDS-PAGE, BN-PAGE, absorption and EPR spectroscopy. Highly uniform supercomplex particles in electron microscopy analysis support a distinct structural composition. The supercomplex possesses a dimeric stoichiometry with a ratio of a-type, b-type and c-type hemes close to 1:1:1. Redox titrations revealed a low potential bcc complex (Em(ISP)=+160mV, Em(bL)=-291mV, Em(bH)=-163mV, Em(cc)=+100mV) fined-tuned for oxidation of menaquinol and a mixed potential aa3 oxidase (Em(CuA)=+150mV, Em(a/a3)=+143/+317mV) mediating between low and high redox potential to accomplish dioxygen reduction. The generated molecular model supports a stable assembled supercomplex with defined architecture which permits energetically efficient coupling of menaquinol oxidation and dioxygen reduction in one supramolecular entity. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Lysine: Participation in life, production and biosynthesis

    International Nuclear Information System (INIS)

    Shah, A.H.; Hameed, A.

    2002-01-01

    Lysine plays a vital role in life. Its demands increase worldwide. It is in the interest of students to advertise the supreme importance of its productions. In this report, the mechanism and the biosynthetic pathway of lysine in corynebacterium glutamicum is illustrated, in a simple and ready understandable way. These will pave the way of lysine production. (author)

  14. Base-Catalyzed Depolymerization of Solid Lignin-Rich Streams Enables Microbial Conversion

    DEFF Research Database (Denmark)

    Rodriguez, Alberto; Salvachúa, Davinia; Katahira, Rui

    2017-01-01

    hydroxycinnamic acids. BCD liquors were tested for microbial growth using seven aromatic-catabolizing bacteria and two yeasts. Three organisms (Pseudomonas putida KT2440, Rhodotorula mucilaginosa, and Corynebacterium glutamicum) tolerate high BCD liquor concentrations (up to 90% v/v) and rapidly consume the main...

  15. Restoration of prostaglandin E2-producing splenic macrophages in 89Sr-treated mice with bone marrow from Corynebacterium parvum primed donors

    International Nuclear Information System (INIS)

    Shibata, Y.

    1989-01-01

    Administration of Corynebacterium parvum (CP), 56 mg/kg ip to CBA/J mice effected the induction of prostaglandin E2 (PGE2) producing macrophages (M phi) in the bone marrow and the spleen. Maximal release of PGE2 from M phi cultured in vitro with calcium ionophore A23187 for 2 h was reached by marrow M phi removed on 5 days after CP (450 ng/mg cell protein), and by splenic M phi 9 days after CP (400 ng/mg). Neither M phi population, however, yielded more than 6.0 ng/mg leukotriene C4. To assess ontogenic relationships mice were depleted of bone marrow and blood monocytes by iv injection of the bone-seeking isotope, 89Sr. CP was given at several points before or after bone marrow cell depletion. PGE2 production by splenic M phi harvested on day 9 after CP was profoundly impaired when CP was administered either concurrently with or 3 days after 89Sr. When CP was administered 1, 3, 5, and 7 days before 89Sr, however, the induction of PGE2-producing M phi in the spleen was unaffected. To determine whether bone marrow cells from CP-injected donors can restore PGE2-producing splenic M phi (PGSM) in 89Sr-mice, recipient mice which had and had not received CP 3 days after 89Sr were transfused with 5 x 10(6) syngeneic bone marrow cells from donor mice prepared at varying intervals after CP administration. The results clearly indicate the capacity of bone marrow cells harvested on either day 1 or 2 following CP to restore PGSM in CP-primed, but not unprimed, recipients

  16. Rapid hybrid de novo assembly of a microbial genome using only short reads: Corynebacterium pseudotuberculosis I19 as a case study.

    Science.gov (United States)

    Cerdeira, Louise Teixeira; Carneiro, Adriana Ribeiro; Ramos, Rommel Thiago Jucá; de Almeida, Sintia Silva; D'Afonseca, Vivian; Schneider, Maria Paula Cruz; Baumbach, Jan; Tauch, Andreas; McCulloch, John Anthony; Azevedo, Vasco Ariston Carvalho; Silva, Artur

    2011-08-01

    Due to the advent of the so-called Next-Generation Sequencing (NGS) technologies the amount of monetary and temporal resources for whole-genome sequencing has been reduced by several orders of magnitude. Sequence reads can be assembled either by anchoring them directly onto an available reference genome (classical reference assembly), or can be concatenated by overlap (de novo assembly). The latter strategy is preferable because it tends to maintain the architecture of the genome sequence the however, depending on the NGS platform used, the shortness of read lengths cause tremendous problems the in the subsequent genome assembly phase, impeding closing of the entire genome sequence. To address the problem, we developed a multi-pronged hybrid de novo strategy combining De Bruijn graph and Overlap-Layout-Consensus methods, which was used to assemble from short reads the entire genome of Corynebacterium pseudotuberculosis strain I19, a bacterium with immense importance in veterinary medicine that causes Caseous Lymphadenitis in ruminants, principally ovines and caprines. Briefly, contigs were assembled de novo from the short reads and were only oriented using a reference genome by anchoring. Remaining gaps were closed using iterative anchoring of short reads by craning to gap flanks. Finally, we compare the genome sequence assembled using our hybrid strategy to a classical reference assembly using the same data as input and show that with the availability of a reference genome, it pays off to use the hybrid de novo strategy, rather than a classical reference assembly, because more genome sequences are preserved using the former. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Outbreak investigation for toxigenic Corynebacterium diphtheriae wound infections in refugees from Northeast Africa and Syria in Switzerland and Germany by whole genome sequencing.

    Science.gov (United States)

    Meinel, D M; Kuehl, R; Zbinden, R; Boskova, V; Garzoni, C; Fadini, D; Dolina, M; Blümel, B; Weibel, T; Tschudin-Sutter, S; Widmer, A F; Bielicki, J A; Dierig, A; Heininger, U; Konrad, R; Berger, A; Hinic, V; Goldenberger, D; Blaich, A; Stadler, T; Battegay, M; Sing, A; Egli, A

    2016-12-01

    Toxigenic Corynebacterium diphtheriae is an important and potentially fatal threat to patients and public health. During the current dramatic influx of refugees into Europe, our objective was to use whole genome sequencing for the characterization of a suspected outbreak of C. diphtheriae wound infections among refugees. After conventional culture, we identified C. diphtheriae using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and investigated toxigenicity by PCR. Whole genome sequencing was performed on a MiSeq Illumina with >70×coverage, 2×250 bp read length, and mapping against a reference genome. Twenty cases of cutaneous C. diphtheriae in refugees from East African countries and Syria identified between April and August 2015 were included. Patients presented with wound infections shortly after arrival in Switzerland and Germany. Toxin production was detected in 9/20 (45%) isolates. Whole genome sequencing-based typing revealed relatedness between isolates using neighbour-joining algorithms. We detected three separate clusters among epidemiologically related refugees. Although the isolates within a cluster showed strong relatedness, isolates differed by >50 nucleotide polymorphisms. Toxigenic C. diphtheriae associated wound infections are currently observed more frequently in Europe, due to refugees travelling under poor hygienic conditions. Close genetic relatedness of C. diphtheriae isolates from 20 refugees with wound infections indicates likely transmission between patients. However, the diversity within each cluster and phylogenetic time-tree analysis suggest that transmissions happened several months ago, most likely outside Europe. Whole genome sequencing offers the potential to describe outbreaks at very high resolution and is a helpful tool in infection tracking and identification of transmission routes. Copyright © 2016. Published by Elsevier Ltd.

  18. Immunoregulation of antitumor response; differential secretion of arachidonic acid metabolites by macrophages during stimulation ''in vitro'' with BCG and ''Corynebacterium parvum''

    International Nuclear Information System (INIS)

    Tomecki, Jaroslaw; Sukiennik, Jadwiga; Kordowiak, Anna

    1993-01-01

    The level of arachidonic acid (AA) metabolites in the supernatants of cultures peritoneal exudate cells (PEC) were studied under various conditions using BCG and ''Corynebacterium parvum'' as stimulators. The metabolite levels were analyzed by thin layer chromatography (TLC). The degree of macrophage cytotoxic/cytostatic activity was dependent on the dose and character of stimulators used and the source of macrophages. The application of micro cytotoxicity assay for the evaluation of tumor cell lysis (lung sarcoma SaL-1) ''in vitro'' revealed that peritoneal macrophages from healthy and tumor bearing BALB/c mice may affect the degree of antitumor response. In the supernatants of cultured PEC from tumor bearing mice AA level increased (by 10-fold) in comparison with PEC from healthy mice. Stimulation with BCG induced over a double level of AA in PEC isolated from tumor bearing mice non-stimulated or stimulated with ''C.parvum''. A lower level of prostaglandins (PGs) was found in the supernatants of cultured PEC isolated from healthy mice (stimulated and non-stimulated), but the highest level of PGs was observed in the supernatants of cultured PEC isolated from tumor bearing mice stimulated with BCG. The unique metabolite of AA was found only in the supernatants form non-stimulated PEC from tumor bearing mice. PEC from tumor bearing mice produced metabolites of AA which were not detected in control group. These results suggest that macrophages also play a regulatory role by secretion of AA. This process can be modified by bacterial antigens. (author). 21 refs, 7 figs

  19. A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hae Joo; Paterson, Neil G. [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Kim, Chae Un [Cornell University, Ithaca, NY 14853 (United States); Middleditch, Martin [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Chang, Chungyu; Ton-That, Hung [University of Texas–Houston Medical School, Houston, TX 77030 (United States); Baker, Edward N., E-mail: ted.baker@auckland.ac.nz [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand)

    2014-05-01

    Two crystal structures of the major pilin SpaD from C. diphtheriae have been determined at 1.87 and 2.5 Å resolution. The N-terminal domain is found to contain an isopeptide bond that forms slowly over time in the recombinant protein. Given its structural context, this provides insight into the relationship between internal isopeptide-bond formation and pilus assembly. The Gram-positive organism Corynebacterium diphtheriae, the cause of diphtheria in humans, expresses pili on its surface which it uses for adhesion and colonization of its host. These pili are covalent protein polymers composed of three types of pilin subunit that are assembled by specific sortase enzymes. A structural analysis of the major pilin SpaD, which forms the polymeric backbone of one of the three types of pilus expressed by C. diphtheriae, is reported. Mass-spectral and crystallographic analysis shows that SpaD contains three internal Lys–Asn isopeptide bonds. One of these, shown by mass spectrometry to be located in the N-terminal D1 domain of the protein, only forms slowly, implying an energy barrier to bond formation. Two crystal structures, of the full-length three-domain protein at 2.5 Å resolution and of a two-domain (D2-D3) construct at 1.87 Å resolution, show that each of the three Ig-like domains contains a single Lys–Asn isopeptide-bond cross-link, assumed to give mechanical stability as in other such pili. Additional stabilizing features include a disulfide bond in the D3 domain and a calcium-binding loop in D2. The N-terminal D1 domain is more flexible than the others and, by analogy with other major pilins of this type, the slow formation of its isopeptide bond can be attributed to its location adjacent to the lysine used in sortase-mediated polymerization during pilus assembly.

  20. The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin.

    Science.gov (United States)

    Küberl, Andreas; Polen, Tino; Bott, Michael

    2016-04-26

    The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which the prokaryotic ubiquitin-like protein Pup is covalently attached to a lysine residue in target proteins, thus resembling ubiquitination in eukaryotes. Pupylated proteins are recognized and unfolded by a dedicated AAA+ ATPase (Mycobacterium proteasomal AAA+ ATPase; ATPase forming ring-shaped complexes). In Mycobacteria, degradation of pupylated proteins by the proteasome serves as a protection mechanism against several stress conditions. Other bacterial genera capable of pupylation such as Corynebacterium lack a proteasome, and the fate of pupylated proteins is unknown. We discovered that Corynebacterium glutamicum mutants lacking components of the pupylation machinery show a strong growth defect under iron limitation, which was caused by the absence of pupylation and unfolding of the iron storage protein ferritin. Genetic and biochemical data support a model in which the pupylation machinery is responsible for iron release from ferritin independent of degradation.

  1. Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats.

    Science.gov (United States)

    Ulich, T R; del Castillo, J; Ni, R X; Bikhazi, N

    1989-06-01

    Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the

  2. Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720 or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis.

    Science.gov (United States)

    Silva, Mara Thais de Oliveira; Bezerra, Francisco Silvestre Brilhante; de Pinho, Rodrigo Barros; Begnini, Karine Rech; Seixas, Fabiana Kommling; Collares, Tiago; Portela, Ricardo Dias; Azevedo, Vasco; Dellagostin, Odir; Borsuk, Sibele

    2018-01-02

    Caseous lymphadenitis (CLA) is a chronic disease responsible for significant economic losses in sheep and goat breeding worldwide. The treatment for this disease is not effective, and an intense vaccination schedule would be the best control strategy. In this study, we evaluated the associations of rCP09720 or rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1), rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two doses of each vaccine at a 21-day interval and were challenged 21 days after the last immunization. The animals were evaluated daily for 40 days after the challenge, and mortality rate was recorded. The total IgG production level increased significantly in the experimental groups on day 42 after the first vaccination. Similarly, higher levels of specific IgG2a were observed in experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4 showed a significant (p < .05) humoral response against both antigens of the antigenic formulations. The cellular immune response induced by immunization was characterized by a significant (p < .05) production of interferon-γ compared to that in the control, while the concentrations of interleukin (IL)-4 and IL-12 were not significant in any group. A significant increase of tumor necrosis factor was observed only in G4. The survival rates after the challenge were 30% (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association of rCP01850 with rPLD resulted in the best protection against the challenge with C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Metabolism and disease

    National Research Council Canada - National Science Library

    Grodzicker, Terri; Stewart, David J; Stillman, Bruce

    2011-01-01

    ...), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer...

  4. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  5. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  6. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  7. Estudo da difteria na cidade do Recife. I. Nota sôbre levantamento de portadores de Corynebacterium diphtheriae no bairro dos Coelhos Survey on diphtheriae carriers in "Bairro dos Coelhos" Recife, Brazil

    Directory of Open Access Journals (Sweden)

    Dalva A. Mello

    1969-06-01

    Full Text Available De uma amostra probabilística do bairro dos Coelhos da cidade do Recife, 410 indivíduos foram examinados para verificação de portadores de difteria. Sòmente duas amostras de C. diphtheriae foram isoladas de duas crianças de 8 a 9 anos, as quais não apresentaram sintomatologia compatível com o quadro diftérico.From a limited population living around the University Hospital in Recife, Brazil a randomic sample was examined in order to identify diphtheria carriers. Swabs were made from 410 persons in a house-to-house survey. Two strains of Corynebacterium diphtheriae were isolated from healthy 8 and 9-year old children.

  8. An in silico platform for the design of heterologous pathways in nonnative metabolite production

    Directory of Open Access Journals (Sweden)

    Chatsurachai Sunisa

    2012-05-01

    Full Text Available Abstract Background Microorganisms are used as cell factories to produce valuable compounds in pharmaceuticals, biofuels, and other industrial processes. Incorporating heterologous metabolic pathways into well-characterized hosts is a major strategy for obtaining these target metabolites and improving productivity. However, selecting appropriate heterologous metabolic pathways for a host microorganism remains difficult owing to the complexity of metabolic networks. Hence, metabolic network design could benefit greatly from the availability of an in silico platform for heterologous pathway searching. Results We developed an algorithm for finding feasible heterologous pathways by which nonnative target metabolites are produced by host microorganisms, using Escherichia coli, Corynebacterium glutamicum, and Saccharomyces cerevisiae as templates. Using this algorithm, we screened heterologous pathways for the production of all possible nonnative target metabolites contained within databases. We then assessed the feasibility of the target productions using flux balance analysis, by which we could identify target metabolites associated with maximum cellular growth rate. Conclusions This in silico platform, designed for targeted searching of heterologous metabolic reactions, provides essential information for cell factory improvement.

  9. diphtheriae in a child Corynebacterium

    African Journals Online (AJOL)

    isolated from blood cultures in suspected cases of. lE. Hpwever, his .... dextrin -, maltose +, sucrose -, catalase +,glucose +, mannitol-, trehalose -, nitrate ... by Abbott.9 Whether in acquired or congenital heart disease, the bacteraemia of lE is ...

  10. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

    The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

  11. Metabolic syndrome and menopause

    OpenAIRE

    Jouyandeh, Zahra; Nayebzadeh, Farnaz; Qorbani, Mostafa; Asadi, Mojgan

    2013-01-01

    Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria t...

  12. [Metabolic functions and sport].

    Science.gov (United States)

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

  13. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  14. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J; Davis, E J

    1973-01-01

    The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

  15. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  16. Investigation of metabolic encephalopathy

    African Journals Online (AJOL)

    cycle defects is the X-linked recessive disorder, ornithine ... life, or if the child is fed the compounds that they are unable .... as learning difficulties, drowsiness and avoidance of ... Table 2. Laboratory investigation of suspected metabolic encephalopathy. Laboratory .... Clinical approach to treatable inborn metabolic diseases:.

  17. Metabolic regulation of inflammation.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  18. Metabolic syndrome and menopause

    Directory of Open Access Journals (Sweden)

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  19. Characterization and sequence analysis of the F2 promoter from corynephage BFK20

    International Nuclear Information System (INIS)

    Koptides, M.; Ugorcakova, J.; Baloghova, E.; Bukovska, G.; Timko, J.

    1994-01-01

    F2 promoter from corynephage BFK20 was isolated and characterized. It was functional in Escherichia coli and Corynebacterium glutamicum. Cloning of the F2 promoter into the pJUP05 promoter probe vector caused an increase of the neomycin phosphotransferase II specific activity. According to the Northern blot hybridization the nptII gene was expressed from the cloned F2 promoter. The apparent transcription start point in E. coli and C. glutamicum was determined. The-35 region of F2 promoter showed high similarity to that of E. coli promoter consensus sequence, but its - 10 region was G+C rich and had no significant homology to that. (author)

  20. Drug metabolism in birds

    Science.gov (United States)

    Pan, Huo Ping; Fouts, James R.

    1979-01-01

    Papers published over 100 years since the beginning of the scientific study of drug metabolism in birds were reviewed. Birds were found to be able to accomplish more than 20 general biotransformation reactions in both functionalization and conjugation. Chickens were the primary subject of study but over 30 species of birds were used. Large species differences in drug metabolism exist between birds and mammals as well as between various birds, these differences were mostly quantitative. Qualitative differences were rare. On the whole, drug metabolism studies in birds have been neglected as compared with similar studies on insects and mammals. The uniqueness of birds and the advantages of using birds in drug metabolism studies are discussed. Possible future studies of drug metabolism in birds are recommended.

  1. Metabolic imaging using SPECT

    International Nuclear Information System (INIS)

    Taki, Junichi; Matsunari, Ichiro

    2007-01-01

    In normal condition, the heart obtains more than two-thirds of its energy from the oxidative metabolism of long chain fatty acids, although a wide variety of substrates such as glucose, lactate, ketone bodies and amino acids are also utilised. In ischaemic myocardium, on the other hand, oxidative metabolism of free fatty acid is suppressed and anaerobic glucose metabolism plays a major role in residual oxidative metabolism. Therefore, metabolic imaging can be an important technique for the assessment of various cardiac diseases and conditions. In SPECT, several iodinated fatty acid traces have been introduced and studied. Of these, 123 I-labelled 15-(p-iodophenyl)3-R, S-methylpentadecanoic acid (BMIPP) has been the most commonly used tracer in clinical studies, especially in some of the European countries and Japan. In this review article, several fatty acid tracers for SPECT are characterised, and the mechanism of uptake and clinical utility of BMIPP are discussed in detail. (orig.)

  2. Mycobacterium tuberculosis Metabolism

    Science.gov (United States)

    Warner, Digby F.

    2015-01-01

    Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

  3. Metabolic Engineering VII Conference

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  4. Metabolic imaging using PET

    International Nuclear Information System (INIS)

    Kudo, Takashi

    2007-01-01

    There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

  5. Astrocytes and energy metabolism.

    Science.gov (United States)

    Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

    2011-05-01

    Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

  6. Metabolic disorders in menopause

    Directory of Open Access Journals (Sweden)

    Grzegorz Stachowiak

    2015-04-01

    Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  7. VRML metabolic network visualizer.

    Science.gov (United States)

    Rojdestvenski, Igor

    2003-03-01

    A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

  8. Human Body Exergy Metabolism

    OpenAIRE

    Mady, Carlos Eduardo Keutenedjian

    2013-01-01

    The exergy analysis of the human body is a tool that can provide indicators of health and life quality. To perform the exergy balance it is necessary to calculate the metabolism on an exergy basis, or metabolic exergy, although there is not yet consensus in its calculation procedure. Hence, the aim of this work is to provide a general method to evaluate this physical quantity for human body based on indirect calorimetry data. To calculate the metabolism on an exergy basis it is necessary to d...

  9. What is Nutrition & Metabolism?

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  10. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  11. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  12. The metabolic radiotherapy

    International Nuclear Information System (INIS)

    Begon, F.; Gaci, M.

    1993-01-01

    In this article, the authors recall the principles of the metabolic radiotherapy and present these main applications in the treatment of thyroid cancers, hyperthyroidism, polycythemia, arthritis, bone metastases, adrenergic neoplasms. They also present the radioimmunotherapy

  13. Engineering of metabolic control

    Science.gov (United States)

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  14. Oxidative metabolism in muscle.

    OpenAIRE

    Ferrari, M; Binzoni, T; Quaresima, V

    1997-01-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantage...

  15. Tumor Macroenvironment and Metabolism

    OpenAIRE

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  16. Ca-48 metabolism studies

    International Nuclear Information System (INIS)

    Van der Merwe, D.G.

    1987-03-01

    Calcium metabolism has been studied in depth physiologically and is a relatively well-understood element in biochemistry and medicine. There is still only restricted knowledge of the metabolic fate of calcium in normal and abnormal paediatric subjects. The latter is partially owing to inadequate techniques for tracing and modelling calcium pathways in children. The advent of radioactive tracers has unquestionably enhanced medical research and improved the quality of many metabolic studies. The present study was aimed at the development, promotion and justification of a new tracer technique using the stable isotope, calcium-48. The obvious advantages of such a technique are its harmlessness tothe subject, its applicability to both short- and long-term studies as well as its usefulness to the study for which it was originally motivated, viz research defining the actual relationship between a calcium-deficient diet and the occurrence of rickets in rural Black children in South Africa. Exploratory instrumental analyses were performed specifically with serum samples. This proved successful enough to develop a less specific pre-concentration technique which improved the sensitivity and reduces the cost of doing calcium-48 metabolism studies. The results of a simple metabolic study are presented whereby the scope of the technique is demonstrated in a real situation. The possibilities and limitations of double-isotope metabolic studies are discussed, particularly with regard to strontium as the second tracer

  17. Genetic relationships of Corynebacterium diphtheriae strains isolated from a diphtheria case and carriers by restriction fragment length polymorphism of rRNA genes Relação genética de cepas de Corynebacterium diphtheriae isoladas de caso e seus contatos por RLFP de rRNA gene

    Directory of Open Access Journals (Sweden)

    Claudio Tavares Sacchi

    1995-08-01

    Full Text Available In the present study we report the results of an analysis, based on ribotyping of Corynebacterium diphtheriae intermedius strains isolated from a 9 years old child with clinical diphtheria and his 5 contacts. Quantitative analysis of RFLPs of rRNA was used to determine relatedness of these 7 C.diphtheriae strains providing support data in the diphtheria epidemiology. We have also tested those strains for toxigenicity in vitro by using the Elek's gel diffusion method and in vivo by using cell culture method on cultured monkey kidney cell (VERO cells. The hybridization results revealed that the 5 C.diphtheriae strains isolated from contacts and one isolated from the clinical case (nose case strain had identical RFLP patterns with all 4 restriction endonucleases used, ribotype B. The genetic distance from this ribotype and ribotype A (throat case strain, that we initially assumed to be responsible for the illness of the patient, was of 0.450 showing poor genetic correlation among these two ribotypes. We found no significant differences concerned to the toxin production by using the cell culture method. In conclusion, the use of RFLPs of rRNA gene was successful in detecting minor differences in closely related toxigenic C.diphtheriae intermedius strains and providing information about genetic relationships among them.No presente estudo, nós reportamos os resultados de uma análise, baseada na ribotipagem de cepas de C. diphtheriae intermedius isoladas de uma criança de 9 anos com difteria e seus 5 contatos. Análise quantitativa por RFLP de rRNA foi usada para determinar a relação destas 7 cepas de C. diphtheriae fornecendo dados de interesse epidemiológico. Nós também testamos estas cepas para toxicidade in vitro usando método de difusão de Elek e in vivo usando método de cultura celular com células VERO. Os resultados de hibridização revelaram que as 5 cepas de C. diphtheriae isoladas dos contatos e uma isolada do caso (cepa isolada

  18. Vertigo and metabolic disorders.

    Science.gov (United States)

    Santos, Maruska D' Aparecida; Bittar, Roseli Saraiva Moreira

    2012-01-01

    Metabolic disorders are accepted by many authors as being responsible for balance disorders. Because of the importance of metabolic disorders in the field of labyrinthine dysfunction, we decided to assess the prevalence of carbohydrates, lipids and thyroid hormones disorders in our patients with vestibular diseases. The study evaluates the metabolic profile of 325 patients with vertigo who sought the Otolaryngology Department of the University of São Paulo in the Hospital das Clínicas da Universidade de São Paulo. The laboratory tests ordered according to the classical research protocol were: low-density lipoprotein cholesterol fraction, TSH, T3, T4 and fasting blood sugar level. The metabolic disorders found and the ones that were observed in the general population were compared. The high level of low-density lipoprotein cholesterol, the altered levels of thyroid hormones, the higher prevalence of diabetes mellitus were the most significant changes found in the group of study. The higher amount of metabolic disorders in patients with vertigo disease reinforces the hypothesis of its influence on the etiopathogenesis of cochleovestibular symptoms.

  19. Metabolic surgery: quo vadis?

    Science.gov (United States)

    Ramos-Leví, Ana M; Rubio Herrera, Miguel A

    2014-01-01

    The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  20. Metabolism of phencyclidine

    International Nuclear Information System (INIS)

    Hoag, M.K.P.

    1987-01-01

    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s)

  1. Microbial production host selection for converting second-generation feedstocks into bioproducts

    Directory of Open Access Journals (Sweden)

    van Groenestijn Johan W

    2009-12-01

    Full Text Available Abstract Background Increasingly lignocellulosic biomass hydrolysates are used as the feedstock for industrial fermentations. These biomass hydrolysates are complex mixtures of different fermentable sugars, but also inhibitors and salts that affect the performance of the microbial production host. The performance of six industrially relevant microorganisms, i.e. two bacteria (Escherichia coli and Corynebacterium glutamicum, two yeasts (Saccharomyces cerevisiae and Pichia stipitis and two fungi (Aspergillus niger and Trichoderma reesei were compared for their (i ability to utilize monosaccharides present in lignocellulosic hydrolysates, (ii resistance against inhibitors present in lignocellulosic hydrolysates, (iii their ability to utilize and grow on different feedstock hydrolysates (corn stover, wheat straw, sugar cane bagasse and willow wood. The feedstock hydrolysates were generated in two manners: (i thermal pretreatment under mild acid conditions followed by enzymatic hydrolysis and (ii a non-enzymatic method in which the lignocellulosic biomass is pretreated and hydrolyzed by concentrated sulfuric acid. Moreover, the ability of the selected hosts to utilize waste glycerol from the biodiesel industry was evaluated. Results Large differences in the performance of the six tested microbial production hosts were observed. Carbon source versatility and inhibitor resistance were the major discriminators between the performances of these microorganisms. Surprisingly all 6 organisms performed relatively well on pretreated crude feedstocks. P. stipitis and A. niger were found to give the overall best performance C. glutamicum and S. cerevisiae were shown to be the least adapted to renewable feedstocks. Conclusion Based on the results obtained we conclude that a substrate oriented instead of the more commonly used product oriented approach towards the selection of a microbial production host will avoid the requirement for extensive metabolic

  2. Metabolic changes in malnutrition.

    Science.gov (United States)

    Emery, P W

    2005-10-01

    This paper is concerned with malnutrition caused by inadequate intake of all the major nutrients rather than deficiency diseases relating to a single micronutrient. Three common situations are recognised: young children in third world countries with protein-energy malnutrition; adults in the same countries who are chronically adapted to subsisting on marginally inadequate diets; and patients who become malnourished as a result of chronic diseases. In all these situations infectious diseases are often also present, and this complicates the interpretation of biochemical and physiological observations. The metabolic response to starvation is primarily concerned with maintaining a supply of water-soluble substrates to supply energy to the brain. Thus there is an initial rise in metabolic rate, reflecting gluconeogenic activity. As fasting progresses, gluconeogenesis is suppressed to minimise muscle protein breakdown and ketones become the main fuel for the brain. With chronic underfeeding the basal metabolic rate per cell appears to fall, but the mechanistic basis for this is not clear. The main adaptation to chronic energy deficiency is slow growth and low adult body size, although the reduction in energy requirement achieved by this is partially offset by the preservation of the more metabolically active organs at the expense of muscle, which has a lower metabolic rate. The interaction between malnutrition and the metabolic response to trauma has been studied using an animal model. The rise in energy expenditure and urinary nitrogen excretion following surgery were significantly attenuated in malnourished rats, suggesting that malnutrition impairs the ability of the body to mobilise substrates to support inflammatory and reparative processes. However, the healing process in wounded muscle remained unimpaired in malnutrition, suggesting that this process has a high biological priority.

  3. Urea metabolism in plants.

    Science.gov (United States)

    Witte, Claus-Peter

    2011-03-01

    Urea is a plant metabolite derived either from root uptake or from catabolism of arginine by arginase. In agriculture, urea is intensively used as a nitrogen fertilizer. Urea nitrogen enters the plant either directly, or in the form of ammonium or nitrate after urea degradation by soil microbes. In recent years various molecular players of plant urea metabolism have been investigated: active and passive urea transporters, the nickel metalloenzyme urease catalyzing the hydrolysis of urea, and three urease accessory proteins involved in the complex activation of urease. The degradation of ureides derived from purine breakdown has long been discussed as a possible additional metabolic source for urea, but an enzymatic route for the complete hydrolysis of ureides without a urea intermediate has recently been described for Arabidopsis thaliana. This review focuses on the proteins involved in plant urea metabolism and the metabolic sources of urea but also addresses open questions regarding plant urea metabolism in a physiological and agricultural context. The contribution of plant urea uptake and metabolism to fertilizer urea usage in crop production is still not investigated although globally more than half of all nitrogen fertilizer is applied to crops in the form of urea. Nitrogen use efficiency in crop production is generally well below 50% resulting in economical losses and creating ecological problems like groundwater pollution and emission of nitric oxides that can damage the ozone layer and function as greenhouse gasses. Biotechnological approaches to improve fertilizer urea usage bear the potential to increase crop nitrogen use efficiency. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Nitrile Metabolizing Yeasts

    Science.gov (United States)

    Bhalla, Tek Chand; Sharma, Monica; Sharma, Nitya Nand

    Nitriles and amides are widely distributed in the biotic and abiotic components of our ecosystem. Nitrile form an important group of organic compounds which find their applications in the synthesis of a large number of compounds used as/in pharmaceutical, cosmetics, plastics, dyes, etc>. Nitriles are mainly hydro-lyzed to corresponding amide/acid in organic chemistry. Industrial and agricultural activities have also lead to release of nitriles and amides into the environment and some of them pose threat to human health. Biocatalysis and biotransformations are increasingly replacing chemical routes of synthesis in organic chemistry as a part of ‘green chemistry’. Nitrile metabolizing organisms or enzymes thus has assumed greater significance in all these years to convert nitriles to amides/ acids. The nitrile metabolizing enzymes are widely present in bacteria, fungi and yeasts. Yeasts metabolize nitriles through nitrilase and/or nitrile hydratase and amidase enzymes. Only few yeasts have been reported to possess aldoxime dehydratase. More than sixty nitrile metabolizing yeast strains have been hither to isolated from cyanide treatment bioreactor, fermented foods and soil. Most of the yeasts contain nitrile hydratase-amidase system for metabolizing nitriles. Transformations of nitriles to amides/acids have been carried out with free and immobilized yeast cells. The nitrilases of Torulopsis candida>and Exophiala oligosperma>R1 are enantioselec-tive and regiospecific respectively. Geotrichum>sp. JR1 grows in the presence of 2M acetonitrile and may have potential for application in bioremediation of nitrile contaminated soil/water. The nitrilase of E. oligosperma>R1 being active at low pH (3-6) has shown promise for the hydroxy acids. Immobilized yeast cells hydrolyze some additional nitriles in comparison to free cells. It is expected that more focus in future will be on purification, characterization, cloning, expression and immobilization of nitrile metabolizing

  5. Hypothyroidism in metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2012-01-01

    Full Text Available Aim: Metabolic syndrome (MetS and hypothyroidism are well established forerunners of atherogenic cardiovascular disease. Considerable overlap occurs in the pathogenic mechanisms of atherosclerotic cardiovascular disease by metabolic syndrome and hypothyroidism. Insulin resistance has been studied as the basic pathogenic mechanism in metabolic syndrome. [1] This cross sectional study intended to assess thyroid function in patients with metabolic syndrome and to investigate the association between hypothyroidism and metabolic syndrome. Materials and Methods: One hundred patients with metabolic syndrome who fulfilled the National Cholesterol Education Program- Adult Treatment Panel (NCEP-ATP III criteria [ 3 out of 5 criteria positive namely blood pressure ≥ 130/85 mm hg or on antihypertensive medications, fasting plasma glucose > 100 mg/dl or on anti-diabetic medications, fasting triglycerides > 150 mg/dl, high density lipoprotein cholesterol (HDL-C 102 cms in men and 88 cms in women] were included in the study group. [2] Fifty patients who had no features of metabolic syndrome (0 out of 5 criteria for metabolic syndrome were included in the control group. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions and lipid levels and those who are under treatment for any thyroid related disorder were excluded from the study. Acutely ill patients were excluded taking into account sick euthyroid syndrome. Patients were subjected to anthropometry, evaluation of vital parameters, lipid and thyroid profile along with other routine laboratory parameters. Students t-test, Chi square test and linear regression, multiple logistic regression models were used for statistical analysis. P value < 0.05 was considered significant. Results: Of the 100 patients in study group, 55 were females (55% and 45 were males (45%. Of the 50

  6. Metabolic complications in oncology

    International Nuclear Information System (INIS)

    Sycova-Mila, Z.

    2012-01-01

    Currently, a lot of space and time is devoted to the therapy of oncologic diseases itself. To reach the good therapy results, complex care of the oncologic patient is needed. Management of complications linked with the disease itself and management of complications emerged after administration of chemotherapy, radiotherapy or targeted therapy, plays a significant role. In addition to infectious, hematological, neurological, cardiac or other complications, metabolic complications are relatively extensive and serious. One of the most frequent metabolic complications in oncology is tumor lysis syndrome, hyperuricemia, hypercalcaemia and syndrome of inappropriate secretion of antidiuretic hormone. (author)

  7. Prokaryote metabolism activity

    OpenAIRE

    Biederman, Lori

    2017-01-01

    I wrote this activity to emphasize that prokaryotic organisms can carry out 6 different types of metabolisms (as presented in Freeman’s Biological Science textbook) and this contrasts to eukaryotes, which can only use 2 metabolism pathways (photoautotroph and heterotroph).    For in class materials I remove the  red box (upper right corner) and print slides 3-10, place them back-to-back and laminate them.  The students get a key (slide 2) and a two-sided organism sheet...

  8. Postgenomic approaches to using corynebacteria as biocatalysts.

    Science.gov (United States)

    Vertès, Alain A; Inui, Masayuki; Yukawa, Hideaki

    2012-01-01

    Corynebacterium glutamicum exhibits numerous ideal intrinsic attributes as a factory of primary and secondary metabolites. The versatile capabilities of this organism have long been implemented at the industrial scale to produce an array of amino acids at high yields and conversion rates, thereby enabling the development of an entire industry. The postgenomic era provides a new technological platform not only to further optimize the intrinsic attributes of C. glutamicum whole cells as biocatalysts, but also to dramatically expand the product portfolio that can be manufactured by this organism, from amino acids to commodity chemicals. This review addresses the methods and strain optimization strategies enabled by genomic information and associated techniques. Their implementation has provided important additional incremental improvements to the economics of industry-scale manufacturing in which C. glutamicum and its episomal elements are used as a performing host-vector system.

  9. Study of molasses / vinasse waste ratio for single cell protein and total microorganisms

    Directory of Open Access Journals (Sweden)

    Marcia Luciana Cazetta

    2006-02-01

    Full Text Available Different molasses/ vinasse ratio were used as substrate to investigate single cell protein and total lipids production by five microorganisms: four yeasts strains: Candida lipolytica, Rhodotorula mucilaginosa, Saccharomyces cerevisiae, a yeast isolated from vinasse lake (denominated LLV98 and a bacterium strain, Corynebacterium glutamicum. The media utilized were: a 50% molasses and 50% vinasse; b 25% molasses and 75% vinasse and c 75% molasses and 25% vinasse. The objective of this work was to study the growth of microorganisms and also evaluate protein and lipids content in the biomass obtained from these by-products. The highest single cell protein production was obtained by S. cerevisiae, 50.35%, followed by R. mucilaginosa, 41.96%. The lowest productions were obtained by C. glutamicum. The higher total lipids productions, more than 26%, were founded in molasses plus vinasse at 50%/50% by S. cerevisiae and C. glutamicum.

  10. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  11. Sleep and Metabolism: An Overview

    Directory of Open Access Journals (Sweden)

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  12. Neonatal nutrition and metabolism

    National Research Council Canada - National Science Library

    Thureen, Patti J; Hay, William W

    2006-01-01

    ..., the volume highlights the important longterm effects of fetal and neonatal growth on health in later life. In addition, there are very practical chapters on methods and techniques for assessing nutritional status, body composition, and evaluating metabolic function. Written by an authoritative, international team of cont...

  13. Insect flight muscle metabolism

    NARCIS (Netherlands)

    Horst, D.J. van der; Beenakkers, A.M.Th.; Marrewijk, W.J.A. van

    1984-01-01

    The flight of an insect is of a very complicated and extremely energy-demanding nature. Wingbeat frequency may differ between various species but values up to 1000 Hz have been measured. Consequently metabolic activity may be very high during flight and the transition from rest to flight is

  14. Sleep and metabolic function.

    Science.gov (United States)

    Morselli, Lisa L; Guyon, Aurore; Spiegel, Karine

    2012-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.

  15. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  16. Metabolism of femoxetine

    International Nuclear Information System (INIS)

    Larsson, H.; Lund, J.

    1981-01-01

    The metabolism of femoxetine, a serotonin uptake inhibitor, has been investigated in rats, dogs, monkeys, and human subjects using two 14 C-femoxetine compounds with labelling in different positions. The metabolic pathways were oxidations (and glucuronidation) and demethylation, both reactions most probably taking place in the liver. Nearly all femoxetine was metabolised, and the same metabolites were found in urine from all four species. Only a small percentage of the radioactivity excreted in the urine was not identified. Rat and dog excreted more N-oxide than monkey and man, while most of the radioactivity (60-100%) in these two species was excreted as two hydroxy metabolites. The metabolic pattern in monkey and man was very similar. About 50% was excreted in these two species as one metabolite, formed by demethylation of a methoxy group. A demethylation of a N-CH 3 group formed an active metabolite, norfemoxetine. The excretion of this metabolite in urine from man varied from 0 to 18% of the dose between individuals. Most of the radioactivity was excreted with the faeces in rat and dog, while monkey and man excreted most of the radioactivity in urine. This difference in excretion route might be explained by the difference in the metabolic pattern. No dose dependency was observed in any of the three animal species investigated. (author)

  17. Tumor macroenvironment and metabolism.

    Science.gov (United States)

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Metabolic Diseases of Muscle

    Science.gov (United States)

    ... here and still get the great care and treatment I received in Michigan.” MDA Is Here to Help You T he Muscular Dystrophy Association offers a vast array of services to help you and your family deal with metabolic diseases of muscle. The staff at your local MDA office is ...

  19. CMRegNet-An interspecies reference database for corynebacterial and mycobacterial regulatory networks

    DEFF Research Database (Denmark)

    Abreu, Vinicius A C; Almeida, Sintia; Tiwari, Sandeep

    2015-01-01

    gene regulatory network can lead to various practical applications, creating a greater understanding of how organisms control their cellular behavior. DESCRIPTION: In this work, we present a new database, CMRegNet for the gene regulatory networks of Corynebacterium glutamicum ATCC 13032......Net to date the most comprehensive database of regulatory interactions of CMNR bacteria. The content of CMRegNet is publicly available online via a web interface found at http://lgcm.icb.ufmg.br/cmregnet ....

  20. Dysregulated metabolism contributes to oncogenesis

    Science.gov (United States)

    Hirschey, Matthew D.; DeBerardinis, Ralph J.; Diehl, Anna Mae E.; Drew, Janice E.; Frezza, Christian; Green, Michelle F.; Jones, Lee W.; Ko, Young H.; Le, Anne; Lea, Michael A.; Locasale, Jason W.; Longo, Valter D.; Lyssiotis, Costas A.; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P.; Pedersen, Peter L.; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Sivanand, Sharanya; Vander Heiden, Matthew G.; Wellen, Kathryn E.

    2015-01-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review “Hallmarks of Cancer”, where the dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results suggest that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  1. Cerebral ketone body metabolism.

    Science.gov (United States)

    Morris, A A M

    2005-01-01

    Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

  2. A Metabolic Race

    Directory of Open Access Journals (Sweden)

    A.M.S. Costa et al.

    2017-07-01

    Full Text Available Metabolic Syndrome describes a set of metabolic risk factors that manifest in an individual and some aspects contribute to its appearance: genetic, overweight and the absence of physical activity. So, a board game was created to simulate the environment and routine experienced by UFF students that could contribute  to the development of Metabolic Syndrome. Players move along a simplified map of Niterói city, where places as Antônio Pedro Hospital (HUAP are pointed out. OBJECTIVES: This project aimed to develop an educational game to consolidate Metabolic Syndrome biochemical events. MATERIAL E METHODS: Each group receives a board, pins, dice, question, challenge and diagnostics cards. One student performs the family doctor function, responsable for delivering cards, reading activities and providing diagnosis to players when game is over.The scoring system is based on 3 criteria for Metabolic Syndrome diagnosis: glycemia, abdominal obesity and HDL cholesterol. At the end of game, it is possible to calculate the rates of each player and provide proportional diagnosis. The winner is the healthiest that first arrives at HUAP. RESULTS AND DISCUSSION: The game was applied to 50 students and only 10% classified the subject-matter as difficult. This finding highlight the need to establish new methods to enhance the teaching and learning process and decrease the students’ dificulties. Students evaluated the game as an important educational support and 85% of them agreed it complements  and consolidate the content discussed in classroom. Finally, the game was very highly rated by students according to their perception about their own performance while playing.  In addition, 95 % students pointed they would play again and 98% said they think games are able to optimize learning. CONCLUSIONS: It was possible not only to approximate biochemical phenomena to the students’ daily life, but also to solidify the theoretical concepts in a dynamic and fun

  3. Can you boost your metabolism?

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000893.htm Can you boost your metabolism? To use the sharing ... boosting metabolism than tactics that work. Some myths can backfire. If you think you are burning more ...

  4. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ... metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration...

  5. Sleep and Metabolism: An Overview

    OpenAIRE

    Sharma, Sunil; Kavuru, Mani

    2010-01-01

    Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways i...

  6. Energy Metabolism in the Liver

    OpenAIRE

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, p...

  7. Pulmonary metabolism of foreign compounds: Its role in metabolic activation

    International Nuclear Information System (INIS)

    Cohen, G.M.

    1990-01-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity

  8. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ..., both under drug pressure and during inhibition. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs.

  9. Solution 1H NMR investigation of the active site molecular and electronic structures of substrate-bound, cyanide-inhibited HmuO, a bacterial heme oxygenase from Corynebacterium diphtheriae.

    Science.gov (United States)

    Li, Yiming; Syvitski, Ray T; Chu, Grace C; Ikeda-Saito, Masao; Mar, Gerd N La

    2003-02-28

    The molecular structure and dynamic properties of the active site environment of HmuO, a heme oxygenase (HO) from the pathogenic bacterium Corynebacterium diphtheriae, have been investigated by (1)H NMR spectroscopy using the human HO (hHO) complex as a homology model. It is demonstrated that not only the spatial contacts among residues and between residues and heme, but the magnetic axes that can be related to the direction and magnitude of the steric tilt of the FeCN unit are strongly conserved in the two HO complexes. The results indicate that very similar contributions of steric blockage of several meso positions and steric tilt of the attacking ligand are operative. A distal H-bond network that involves numerous very strong H-bonds and immobilized water molecules is identified in HmuO that is analogous to that previously identified in hHO (Li, Y., Syvitski, R. T., Auclair, K., Wilks, A., Ortiz de Montellano, P. R., and La Mar, G. N. (2002) J. Biol. Chem. 277, 33018-33031). The NMR results are completely consistent with the very recent crystal structure of the HmuO.substrate complex. The H-bond network/ordered water molecules are proposed to orient the distal water molecule near the catalytically key Asp(136) (Asp(140) in hHO) that stabilizes the hydroperoxy intermediate. The dynamic stability of this H-bond network in HmuO is significantly greater than in hHO and may account for the slower catalytic rate in bacterial HO compared with mammalian HO.

  10. Microglia energy metabolism in metabolic disorder.

    Science.gov (United States)

    Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

    2016-12-15

    Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Metabolic syndrome in hyperprolactinemia

    DEFF Research Database (Denmark)

    Andersen, Marianne; Glintborg, Dorte

    2018-01-01

    The metabolic syndrome (MetS) is a conglomerate of clinical findings that convey into increased morbidity and mortality from type 2 diabetes mellitus (T2D) and cardiovascular disease. Hyperprolactinemia (hyperPRL) is associated with components of MetS, especially during pregnancy. Endogenous levels...... in patients with T2D. HyperPRL is a biomarker for decreased dopaminergic tonus in the hypothalamic-pituitary circuit. Patients with a prolactinoma, patients with schizophrenia and/or T2D often have disturbances in this balance and the finding of lower prolactin (PRL) levels in polycystic ovary syndrome (PCOS......) may indicate increased dopaminergic tonus. Recent studies supported that PRL levels within or above reference range may be differently related to MetS. In healthy study populations and in PCOS, PRL levels were inversely associated with metabolic risk markers. Ongoing research on PRL fragments...

  12. Calcium metabolism in birds.

    Science.gov (United States)

    de Matos, Ricardo

    2008-01-01

    Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

  13. Spectrum of metabolic myopathies.

    Science.gov (United States)

    Angelini, Corrado

    2015-04-01

    Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

  14. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  15. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  16. Maternal cardiac metabolism in pregnancy

    Science.gov (United States)

    Liu, Laura X.; Arany, Zolt

    2014-01-01

    Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

  17. Imaging metabolic heterogeneity in cancer.

    Science.gov (United States)

    Sengupta, Debanti; Pratx, Guillem

    2016-01-06

    As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.

  18. Tumor Metabolism of Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  19. Tumor Metabolism of Malignant Gliomas

    International Nuclear Information System (INIS)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang

    2013-01-01

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation

  20. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic......Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...

  1. Metal metabolism and toxicity

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Whelton, B.D.; Moretti, E.S.; Peterson, D.P.; Oldham, R.D.

    1985-01-01

    This research focuses on the role of pregnancy and lactation in susceptibility to the toxic effects of cadmium and lead. Responses under investigation include lead-induced changes in pathways for vitamin D and calcium metabolism and cadmium-induced alterations in kidney function and skeletal structure. The second area focuses on the gastrointestinal absorption of plutonium and other actinide elements. Studies currently being conducted in nonhuman primates to develop a procedure to determine GI absorption values of uranium and plutonium that does not require sacrifice of the animal. 6 refs

  2. Connecting Myokines and Metabolism

    Directory of Open Access Journals (Sweden)

    Rexford S. Ahima

    2015-09-01

    Full Text Available Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets.

  3. Treatment of metabolic syndrome.

    Science.gov (United States)

    Wagh, Arati; Stone, Neil J

    2004-03-01

    The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin

  4. Metabolic syndrome, diet and exercise.

    Science.gov (United States)

    De Sousa, Sunita M C; Norman, Robert J

    2016-11-01

    Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Metabolic Reprogramming in Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Raquel Guimaraes Coelho

    2018-03-01

    Full Text Available Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer.

  6. Metabolic Reprogramming in Thyroid Carcinoma

    Science.gov (United States)

    Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

    2018-01-01

    Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

  7. Metabolic topography of Parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Seung [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism.

  8. Drug metabolism and ageing.

    Science.gov (United States)

    Wynne, Hilary

    2005-06-01

    Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

  9. Metabolic topography of Parkinsonism

    International Nuclear Information System (INIS)

    Kim, Jae Seung

    2007-01-01

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism

  10. Metabolic regulation of yeast

    Science.gov (United States)

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  11. Inflammation and metabolic disorders.

    Science.gov (United States)

    Navab, Mohamad; Gharavi, Nima; Watson, Andrew D

    2008-07-01

    Poor nutrition, overweight and obesity have increasingly become a public health concern as they affect many metabolic disorders, including heart disease, diabetes, digestive system disorders, and renal failure. Study of the effects of life style including healthy nutrition will help further elucidate the mechanisms involved in the adverse effects of poor nutrition. Unhealthy life style including poor nutrition can result in imbalance in our oxidation/redox systems. Lipids can undergo oxidative modification by lipoxygenases, cyclooxygenases, myeloperoxidase, and other enzymes. Oxidized phospholipids can induce inflammatory molecules in the liver and other organs. This can contribute to inflammation, leading to coronary heart disease, stroke, renal failure, inflammatory bowl disease, metabolic syndrome, bone and joint disorders, and even certain types of cancer. Our antioxidant and antiinflammatory defense mechanisms contribute to a balance between the stimulators and the inhibitors of inflammation. Beyond a point, however, these systems might be overwhelmed and eventually fail. High-density lipoprotein is a potent inhibitor of the formation of toxic oxidized lipids. High-density lipoprotein is also an effective system for stimulating the genes whose products are active in the removal, inactivation, and elimination of toxic lipids. Supporting the high-density lipoprotein function should help maintain the balance in these systems. It is hoped that the present report would elucidate some of the ongoing work toward this goal.

  12. Biochemical Hypermedia: Galactose Metabolism.

    Directory of Open Access Journals (Sweden)

    J.K. Sugai

    2013-05-01

    Full Text Available Introduction: Animations of biochemical processes and virtual laboratory environments lead to true molecular simulations. The use of interactive software’s in education can improve cognitive capacity, better learning and, mainly, it makes information acquisition easier. Material and Methods: This work presents the development of a biochemical hypermedia to understanding of the galactose metabolism. It was developed with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. Results and Discussion: A step by step animation process shows the enzymatic reactions of galactose conversion to glucose-1-phosphate (to glycogen synthesis, glucose-6-phosphate (glycolysis intermediary, UDP-galactose (substrate to mucopolysaccharides synthesis and collagen’s glycosylation. There are navigation guide that allow scrolling the mouse over the names of the components of enzymatic reactions of via the metabolism of galactose. Thus, explanatory text box, chemical structures and animation of the actions of enzymes appear to navigator. Upon completion of the module, the user’s response to the proposed exercise can be checked immediately through text box with interactive content of the answer. Conclusion: This hypermedia was presented for undergraduate students (UFSC who revealed that it was extremely effective in promoting the understanding of the theme.

  13. [Metabolic bone disease osteomalacia].

    Science.gov (United States)

    Reuss-Borst, M A

    2014-05-01

    Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

  14. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

    Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

    2009-01-01

    The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or

  15. Metabolic Adaptation to Muscle Ischemia

    Science.gov (United States)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  16. Gut Microbiota and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Kyu Yeon Hur

    2015-06-01

    Full Text Available Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

  17. Clinical update on metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Juan Diego Hernández-Camacho

    2017-12-01

    Full Text Available Metabolic syndrome has been defined as a global issue since it affects a lot of people. Numerous factors are involved in metabolic syndrome development. It has been described that metabolic syndrome has negative consequences on health. Consequently, a lot of treatments have been proposed to palliate it such as drugs, surgery or life style changes where nutritional habits have shown to be an important point in its management. The current study reviews the literature existing about the actual epidemiology of metabolic syndrome, the components involucrate in its appearance and progression, the clinical consequences of metabolic syndrome and the nutritional strategies reported in its remission. A bibliographic search in PubMed and Medline was performed to identify eligible studies. Authors obtained that metabolic syndrome is present in population from developed and undeveloped areas in a huge scale. Environmental and genetic elements are involucrate in metabolic syndrome development. Metabolic syndrome exponentially increased risk of cardiovascular disease, some types of cancers, diabetes mellitus type 2, sleep disturbances, etc. Nutritional treatments play a crucial role in metabolic syndrome prevention, treatment and recovery.

  18. Discovery and History of Amino Acid Fermentation.

    Science.gov (United States)

    Hashimoto, Shin-Ichi

    There has been a strong demand in Japan and East Asia for L-glutamic acid as a seasoning since monosodium glutamate was found to present umami taste in 1907. The discovery of glutamate fermentation by Corynebacterium glutamicum in 1956 enabled abundant and low-cost production of the amino acid, creating a large market. The discovery also prompted researchers to develop fermentative production processes for other L-amino acids, such as lysine. Currently, the amino acid fermentation industry is so huge that more than 5 million metric tons of amino acids are manufactured annually all over the world, and this number continues to grow. Research on amino acid fermentation fostered the notion and skills of metabolic engineering which has been applied for the production of other compounds from renewable resources. The discovery of glutamate fermentation has had revolutionary impacts on both the industry and science. In this chapter, the history and development of glutamate fermentation, including the very early stage of fermentation of other amino acids, are reviewed.

  19. De novo biosynthesis of vanillin in fission yeast (Schizosaccharomyces pombe) and baker's yeast (Saccharomyces cerevisiae).

    Science.gov (United States)

    Hansen, Esben H; Møller, Birger Lindberg; Kock, Gertrud R; Bünner, Camilla M; Kristensen, Charlotte; Jensen, Ole R; Okkels, Finn T; Olsen, Carl E; Motawia, Mohammed S; Hansen, Jørgen

    2009-05-01

    Vanillin is one of the world's most important flavor compounds, with a global market of 180 million dollars. Natural vanillin is derived from the cured seed pods of the vanilla orchid (Vanilla planifolia), but most of the world's vanillin is synthesized from petrochemicals or wood pulp lignins. We have established a true de novo biosynthetic pathway for vanillin production from glucose in Schizosaccharomyces pombe, also known as fission yeast or African beer yeast, as well as in baker's yeast, Saccharomyces cerevisiae. Productivities were 65 and 45 mg/liter, after introduction of three and four heterologous genes, respectively. The engineered pathways involve incorporation of 3-dehydroshikimate dehydratase from the dung mold Podospora pauciseta, an aromatic carboxylic acid reductase (ACAR) from a bacterium of the Nocardia genus, and an O-methyltransferase from Homo sapiens. In S. cerevisiae, the ACAR enzyme required activation by phosphopantetheinylation, and this was achieved by coexpression of a Corynebacterium glutamicum phosphopantetheinyl transferase. Prevention of reduction of vanillin to vanillyl alcohol was achieved by knockout of the host alcohol dehydrogenase ADH6. In S. pombe, the biosynthesis was further improved by introduction of an Arabidopsis thaliana family 1 UDP-glycosyltransferase, converting vanillin into vanillin beta-D-glucoside, which is not toxic to the yeast cells and thus may be accumulated in larger amounts. These de novo pathways represent the first examples of one-cell microbial generation of these valuable compounds from glucose. S. pombe yeast has not previously been metabolically engineered to produce any valuable, industrially scalable, white biotech commodity.

  20. Synthetic biology for manufacturing chemicals: constraints drive the use of non-conventional microbial platforms.

    Science.gov (United States)

    Czajka, Jeffrey; Wang, Qinhong; Wang, Yechun; Tang, Yinjie J

    2017-10-01

    Genetically modified microbes have had much industrial success producing protein-based products (such as antibodies and enzymes). However, engineering microbial workhorses for biomanufacturing of commodity compounds remains challenging. First, microbes cannot afford burdens with both overexpression of multiple enzymes and metabolite drainage for product synthesis. Second, synthetic circuits and introduced heterologous pathways are not yet as "robust and reliable" as native pathways due to hosts' innate regulations, especially under suboptimal fermentation conditions. Third, engineered enzymes may lack channeling capabilities for cascade-like transport of metabolites to overcome diffusion barriers or to avoid intermediate toxicity in the cytoplasmic environment. Fourth, moving engineered hosts from laboratory to industry is unreliable because genetic mutations and non-genetic cell-to-cell variations impair the large-scale fermentation outcomes. Therefore, synthetic biology strains often have unsatisfactory industrial performance (titer/yield/productivity). To overcome these problems, many different species are being explored for their metabolic strengths that can be leveraged to synthesize specific compounds. Here, we provide examples of non-conventional and genetically amenable species for industrial manufacturing, including the following: Corynebacterium glutamicum for its TCA cycle-derived biosynthesis, Yarrowia lipolytica for its biosynthesis of fatty acids and carotenoids, cyanobacteria for photosynthetic production from its sugar phosphate pathways, and Rhodococcus for its ability to biotransform recalcitrant feedstock. Finally, we discuss emerging technologies (e.g., genome-to-phenome mapping, single cell methods, and knowledge engineering) that may facilitate the development of novel cell factories.

  1. Enhanced production of 3-hydroxypropionic acid from glucose via malonyl-CoA pathway by engineered Escherichia coli.

    Science.gov (United States)

    Cheng, Zhuan; Jiang, Jiaqi; Wu, Hui; Li, Zhimin; Ye, Qin

    2016-01-01

    In this study, production of 3-HP via malonyl-CoA was investigated by using metabolically engineered Escherichia coli carrying heterogeneous acetyl-CoA carboxylase (Acc) from Corynebacterium glutamicum and codon-optimized malonyl-CoA reductase (MCR) from Chloroflexus aurantiacus. Three engineered E. coli strains with different host-vector systems were constructed and investigated. The results indicated that the combination of E. coli BL21(DE3) and pET28a was the most efficient host-vector system for 3-HP production, and the highest concentration of 3-HP attained in shake flask cultivation reached 1.80g/L by the strain BE-MDA with induction at 0.25mM IPTG and 25°C, and supplementation of NaHCO3 and biotin. In fed-batch fermentation performed in a 5-L reactor, the concentration of 3-HP achieved 10.08g/L in 36h. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Metabolic interrelationships software application: Interactive learning tool for intermediary metabolism

    NARCIS (Netherlands)

    A.J.M. Verhoeven (Adrie); M. Doets (Mathijs); J.M.J. Lamers (Jos); J.F. Koster (Johan)

    2005-01-01

    textabstractWe developed and implemented the software application titled Metabolic Interrelationships as a self-learning and -teaching tool for intermediary metabolism. It is used by undergraduate medical students in an integrated organ systems-based and disease-oriented core curriculum, which

  3. Metabolism during hypodynamia

    Science.gov (United States)

    Federov, I. V.

    1980-01-01

    Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

  4. Olfaction Under Metabolic Influences

    Science.gov (United States)

    2012-01-01

    Recently published work and emerging research efforts have suggested that the olfactory system is intimately linked with the endocrine systems that regulate or modify energy balance. Although much attention has been focused on the parallels between taste transduction and neuroendocrine controls of digestion due to the novel discovery of taste receptors and molecular components shared by the tongue and gut, the equivalent body of knowledge that has accumulated for the olfactory system, has largely been overlooked. During regular cycles of food intake or disorders of endocrine function, olfaction is modulated in response to changing levels of various molecules, such as ghrelin, orexins, neuropeptide Y, insulin, leptin, and cholecystokinin. In view of the worldwide health concern regarding the rising incidence of diabetes, obesity, and related metabolic disorders, we present a comprehensive review that addresses the current knowledge of hormonal modulation of olfactory perception and how disruption of hormonal signaling in the olfactory system can affect energy homeostasis. PMID:22832483

  5. Metabolic syndrome and asthma.

    Science.gov (United States)

    Garmendia, Jenny V; Moreno, Dolores; Garcia, Alexis H; De Sanctis, Juan B

    2014-01-01

    Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

  6. Early anaerobic metabolisms

    DEFF Research Database (Denmark)

    Canfield, Donald Eugene; Rosing, Minik T; Bjerrum, Christian

    2006-01-01

    probably driven by the cycling of H2 and Fe2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity......Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were...... of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent...

  7. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  8. Genome scale metabolic modeling of cancer

    DEFF Research Database (Denmark)

    Nilsson, Avlant; Nielsen, Jens

    2017-01-01

    of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome......Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...

  9. A CASE OF METABOLIC SYNDROME

    OpenAIRE

    Khoo Ee Ming; Rabia Khatoon

    2006-01-01

    This case report illustrates a 40-year-old woman who presented with chest discomfort that was subsequently diagnosed to have metabolic syndrome. Metabolic syndrome is a common condition associated with increased cardiovascular morbidity and mortality. As primary care providers, we should be detect this condition early, intervene and prevent appropriately before complications occur.

  10. Artificial Promoters for Metabolic Optimization

    DEFF Research Database (Denmark)

    Jensen, Peter Ruhdal; Hammer, Karin

    1998-01-01

    In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms...

  11. Metabolic alterations in dialysis patients

    NARCIS (Netherlands)

    Drechsler, Christiane

    2010-01-01

    Assessing metabolic risk in dialysis patients, three main aspects are important: a) the pathophysiologic effects of metabolic disturbances as known from the general population are unlikely to completely reverse once patients reach dialysis. b) Specific additional problems related to chronic kidney

  12. Selected Metabolic Responses to Skateboarding

    Science.gov (United States)

    Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

    2011-01-01

    Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

  13. Gait Dynamics and Locomotor Metabolism

    Science.gov (United States)

    2014-12-01

    26 47. Taylor CR, Heglund NC, Maloiy GMO . Energetics and mechanics of terrestrial locomotion. I. Metabolic energy consumption as a function of...San Diego, CA: Academic Press, 1994. 110 47. Taylor CR, Heglund NC, Maloiy GMO . Energetics and mechanics of terrestrial locomotion. I. Metabolic

  14. [Hypovitaminosis D and metabolic syndrome].

    Science.gov (United States)

    Miñambres, Inka; de Leiva, Alberto; Pérez, Antonio

    2014-12-23

    Metabolic syndrome and hypovitaminosis D are 2 diseases with high prevalence that share several risk factors, while epidemiological evidence shows they are associated. Although the mechanisms involved in this association are not well established, hypovitaminosis D is associated with insulin resistance, decreased insulin secretion and activation of the renin-angiotensin system, mechanisms involved in the pathophysiology of metabolic syndrome. However, the apparent ineffectiveness of vitamin D supplementation on metabolic syndrome components, as well as the limited information about the effect of improving metabolic syndrome components on vitamin D concentrations, does not clarify the direction and the mechanisms involved in the causal relationship between these 2 pathologies. Overall, because of the high prevalence and the epidemiological association between both diseases, hypovitaminosis D could be considered a component of the metabolic syndrome. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  15. Vitamin A Metabolism: An Update

    Directory of Open Access Journals (Sweden)

    William S. Blaner

    2011-01-01

    Full Text Available Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years.

  16. The metabolic switch of cancer

    Directory of Open Access Journals (Sweden)

    Yuting Ma

    2017-03-01

    Full Text Available Although remarkable progress has been made in oncology research, cancer is still a leading cause of death worldwide. It is well recognized that cancer is a genetic disease, yet metabolic alterations or reprogramming are the major phenotypes associated with the (epi-genetic modifications of cancer cells. Thus, understanding the metabolic changes of tumor cells will facilitate the diagnosis of cancer, alleviate drug resistance and provide novel druggable targets that can lead to cures for cancer. The first Sino-US Symposium on Cancer Metabolism was held in Chongqing on October 10th and 11th, with the theme of “cancer metabolism and precision cancer therapy”. The symposium brought about a dozen keynote speakers each from the US and mainland China, as well as one hundred delegates with an interest in cancer metabolism. This short article will briefly summarize the advances reported during this meeting.

  17. Metabolic Syndrome and Neuroprotection

    Directory of Open Access Journals (Sweden)

    Melisa Etchegoyen

    2018-04-01

    Full Text Available Introduction: Over the years the prevalence of metabolic syndrome (MetS has drastically increased in developing countries as a major byproduct of industrialization. Many factors, such as the consumption of high-calorie diets and a sedentary lifestyle, bolster the spread of this disorder. Undoubtedly, the massive and still increasing incidence of MetS places this epidemic as an important public health issue. Hereon we revisit another outlook of MetS beyond its classical association with cardiovascular disease (CVD and Diabetes Mellitus Type 2 (DM2, for MetS also poses a risk factor for the nervous tissue and threatens neuronal function. First, we revise a few essential concepts of MetS pathophysiology. Second, we explore some neuroprotective approaches in MetS pertaining brain hypoxia. The articles chosen for this review range from the years 1989 until 2017; the selection criteria was based on those providing data and exploratory information on MetS as well as those that studied innovative therapeutic approaches.Pathophysiology: The characteristically impaired metabolic pathways of MetS lead to hyperglycemia, insulin resistance (IR, inflammation, and hypoxia, all closely associated with an overall pro-oxidative status. Oxidative stress is well-known to cause the wreckage of cellular structures and tissue architecture. Alteration of the redox homeostasis and oxidative stress alter the macromolecular array of DNA, lipids, and proteins, in turn disrupting the biochemical pathways necessary for normal cell function.Neuroprotection: Different neuroprotective strategies are discussed involving lifestyle changes, medication aimed to mitigate MetS cardinal symptoms, and treatments targeted toward reducing oxidative stress. It is well-known that the routine practice of physical exercise, aerobic activity in particular, and a complete and well-balanced nutrition are key factors to prevent MetS. Nevertheless, pharmacological control of MetS as a whole and

  18. Marked Response in Microbial Community and Metabolism in the Ileum and Cecum of Suckling Piglets After Early Antibiotics Exposure

    Directory of Open Access Journals (Sweden)

    Miao Yu

    2018-05-01

    Full Text Available In modern swine husbandry systems, antibiotics have been used as growth promoters for piglets during suckling or weaning period. However, while early colonization of intestinal microbiota has been regarded crucial for the host’s later life performance and well-being, little is known about the impact of antibiotics on intestinal microbiota in suckling piglets. The present study aimed to investigate the effects of early antibiotics exposure on gut microbiota and microbial metabolism of suckling piglets. Sixteen litters of suckling piglets were fed a creep feed diet with (Antibiotic or without (Control antibiotics from postnatal days 7–23 (n = 8. The ileal and cecal digesta were obtained for microbial composition and microbial metabolites analysis. The results showed that the antibiotics significantly altered the bacterial community composition by decreasing (P < 0.05 the diversity and richness in the ileum. The antibiotics significantly reduced the abundance of Lactobacillus in both the ileum and cecum, increased the abundance of Streptococcus, unclassified Enterococcaceae, unclassified Fusobacteriales, and Corynebacterium in the ileum, and the abundance of unclassified Ruminococcaceae and unclassified Erysipelotrichaceae in the cecum. The antibiotics decreased (P < 0.05 ileal lactate concentration and cecal concentration of total short-chain fatty acids (SCFAs. But the antibiotics enhanced protein fermentation (P < 0.05 in the ileum and cecum, as ileal concentrations of putrescine and cadaverine, and cecal concentrations of isobutyrate, isovalerate, putrescine, cadaverine, spermine, and spermidine were significantly increased (P < 0.05. These results indicated that early antibiotics exposure significantly altered the microbial composition of suckling piglets toward a vulnerable and unhealthy gut environment. The findings provide a new insight on the antibiotics impact on neonates and may provide new framework for designing alternatives to the

  19. Metabolic reprogramming during neuronal differentiation.

    Science.gov (United States)

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

  20. Noise effect in metabolic networks

    International Nuclear Information System (INIS)

    Zheng-Yan, Li; Zheng-Wei, Xie; Tong, Chen; Qi, Ouyang

    2009-01-01

    Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states. (cross-disciplinary physics and related areas of science and technology)

  1. Xenobiotic Metabolism and Gut Microbiomes.

    Directory of Open Access Journals (Sweden)

    Anubhav Das

    Full Text Available Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs also indicate geographic as well as age specific trends.

  2. Nutrigenetics of the lipoprotein metabolism.

    Science.gov (United States)

    Garcia-Rios, Antonio; Perez-Martinez, Pablo; Delgado-Lista, Javier; Lopez-Miranda, Jose; Perez-Jimenez, Francisco

    2012-01-01

    It is well known that lipid metabolism is a cornerstone in the development of the commonest important chronic diseases worldwide, such as obesity, cardiovascular disease, or metabolic syndrome. In this regard, the area of lipid and lipoprotein metabolism is one of the areas in which the understanding of the development and progression of those metabolic disorders has been studied in greater depth. Thus, growing evidence has demonstrated that while universal recommendations might be appropriate for the general population, in this area there is great variability among individuals, related to a combination of environmental and genetic factors. Moreover, the interaction between genetic and dietary components has helped in understanding this variability. Therefore, with further study into the interaction between the most important genetic markers or single-nucleotide polymorphisms (SNPs) and diet, it may be possible to understand the variability in lipid metabolism, which could lead to an increase in the use of personalized nutrition as the best support to combat metabolic disorders. This review discusses some of the evidence in which candidate SNPs can affect the key players of lipid metabolism and how their phenotypic manifestations can be modified by dietary intake. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Inherited metabolic disorders in Thailand.

    Science.gov (United States)

    Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

    2002-08-01

    The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

  4. Acyl-Lipid Metabolism

    Science.gov (United States)

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  5. Sphingolipid metabolism diseases.

    Science.gov (United States)

    Kolter, Thomas; Sandhoff, Konrad

    2006-12-01

    Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

  6. Physics of metabolic organization

    Science.gov (United States)

    Jusup, Marko; Sousa, Tânia; Domingos, Tiago; Labinac, Velimir; Marn, Nina; Wang, Zhen; Klanjšček, Tin

    2017-03-01

    We review the most comprehensive metabolic theory of life existing to date. A special focus is given to the thermodynamic roots of this theory and to implications that the laws of physics-such as the conservation of mass and energy-have on all life. Both the theoretical foundations and biological applications are covered. Hitherto, the foundations were more accessible to physicists or mathematicians, and the applications to biologists, causing a dichotomy in what always should have been a single body of work. To bridge the gap between the two aspects of the same theory, we (i) adhere to the theoretical formalism, (ii) try to minimize the amount of information that a reader needs to process, but also (iii) invoke examples from biology to motivate the introduction of new concepts and to justify the assumptions made, and (iv) show how the careful formalism of the general theory enables modular, self-consistent extensions that capture important features of the species and the problem in question. Perhaps the most difficult among the introduced concepts, the utilization (or mobilization) energy flow, is given particular attention in the form of an original and considerably simplified derivation. Specific examples illustrate a range of possible applications-from energy budgets of individual organisms, to population dynamics, to ecotoxicology.

  7. The metabolism of biphenyl

    International Nuclear Information System (INIS)

    Meyer, T.; Aarbakke, J.; Scheline, R.R.

    1976-01-01

    The metabolic disposition of 14 C-biphenyl in the rat was studied by liquid scintillation counting. The rats were given an oral dose of 14 C-biphenyl (100 mg/kg, 0.7-1.0 μci) and the total excretion of radioactivity after 96 hrs was 92.2% of the dose. Urinary excretion accounted for 84.8% and faecal excretion for 7.3% of the dose. Most of this radioactivity, 75.8% and 5.8% respectively, was excreted within 24 hrs. Only trace amounts of 14 CO 2 were detected in the expired air and 0.6% of the dose was found to be still present in the rats 96 hrs after biphenyl administration. Extraction and fractionation of the 24 hrs urine samples showed that the largest fraction (nearly 30% of the dose) consisted of conjugated phenolic metabolites. Acidic metabolites accounted for a quarter of the dose and the low levels of expired 14 CO 2 indicated that these were not products resulting from extensive degradation and decarboxylation. (author)

  8. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  9. Carbohydrate metabolism in catfish

    International Nuclear Information System (INIS)

    Saad, C.R.; Lovell, R.T.

    2002-01-01

    Radiolabeled (U- 14 C)-glucose was incorporated in diets and forced-fed to channel catfish and was observed for a 24 hour period. About 95% of fed labeled (U- 14 C)-glucose was absorbed by catfish, showing a high digestibility of glucose. The amounts of 14 C excreted over 24 h as carbon dioxide were 49% and amounts excreted in urine were 3.5%. The amount retained as protein, fat glycogen and other organic compounds were 8.2, 1.2, 6.5 and 32.1 % respectively, for the 24 hour period. The blood concentration of 14 C reached a maximum 2.5 hour after feeding (U- 14 C)-glucose, then gradually decreased. Based on tissue concentrations of 14 C, glycogen was an immediate storage site for absorbed glucose, but 14 C- glycogen in liver decreased rapidly. Glucose was quickly and heavily converted into triglyceride, indicating that fat is an important intermediate in the metabolism of glucose in channel catfish. 14 C-fat in the serum and liver were transferred to the adipose tissue in the muscle and mesentery about 10 hours after feeding. (Author)

  10. Energy Metabolism in the Liver

    Science.gov (United States)

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  11. Mathematical modeling of cancer metabolism.

    Science.gov (United States)

    Medina, Miguel Ángel

    2018-04-01

    Systemic approaches are needed and useful for the study of the very complex issue of cancer. Modeling has a central position in these systemic approaches. Metabolic reprogramming is nowadays acknowledged as an essential hallmark of cancer. Mathematical modeling could contribute to a better understanding of cancer metabolic reprogramming and to identify new potential ways of therapeutic intervention. Herein, I review several alternative approaches to metabolic modeling and their current and future impact in oncology. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Plant metabolic modeling: achieving new insight into metabolism and metabolic engineering.

    Science.gov (United States)

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-10-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. © 2014 American Society of Plant Biologists. All rights reserved.

  13. Metabolic Syndrome in Nurses

    Directory of Open Access Journals (Sweden)

    María Escasany

    2014-01-01

    Full Text Available Objectives: To estimate the prevalence of metabolic syndrome (MS in female nurses in the Hospital Juan A. Fernandez (HJAF, Buenos Aires, Argentina, and to determine whether work, rest, diet, and health, are predictive of it.Materials and methods: For the first objective, a descriptive, observational and cross-sectional study was conducted, and for the second, a multivariate cross-sectional observational multivariate analysis was made comparing independent samples. A total of 192 nurses were studied between October 2008 and March 2009. They completed a questionnaire that include indicators that could be predictors of MS. Anthropometric measurements, including blood pressure were taken, was well as a blood sample to analyze fasting glucose, HDL-C and plasma triglycerides.Results: It was found that 35% and 41% of nurses were overweight and obese, respectively. A total of 92% had centro-abdominal obesity. The prevalence of MS found was 33.3% (95%CI, 26.7 to 40.5. Those who had this disease were between 53±9 years. Statistically significant differences were found in the bivariate analysis between MS and the variables, age, length of service, time worked during night shift, and academic studies.Conclusions: The prevalence of MS was 64/192 in HJAF nurses (33.3% I 95%CI, 26.7-40.5. There were no statistically significant differences with the indicators of, age, “time worked during night shift”, and “studies”. These results suggest that age is the most important variable in predicting the onset of MS in the population of nurses.

  14. Testosterone and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Glenn R Cunningham

    2015-04-01

    Full Text Available Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS. Many of the components are accepted risk factors for cardiovascular disease (CVD. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT and sex hormone binding globulin (SHBG levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  15. Topological analysis of metabolic control.

    Science.gov (United States)

    Sen, A K

    1990-12-01

    A topological approach is presented for the analysis of control and regulation in metabolic pathways. In this approach, the control structure of a metabolic pathway is represented by a weighted directed graph. From an inspection of the topology of the graph, the control coefficients of the enzymes are evaluated in a heuristic manner in terms of the enzyme elasticities. The major advantage of the topological approach is that it provides a visual framework for (1) calculating the control coefficients of the enzymes, (2) analyzing the cause-effect relationships of the individual enzymes, (3) assessing the relative importance of the enzymes in metabolic regulation, and (4) simplifying the structure of a given pathway, from a regulatory viewpoint. Results are obtained for (a) an unbranched pathway in the absence of feedback the feedforward regulation and (b) an unbranched pathway with feedback inhibition. Our formulation is based on the metabolic control theory of Kacser and Burns (1973) and Heinrich and Rapoport (1974).

  16. Neuroinflammatory basis of metabolic syndrome.

    Science.gov (United States)

    Purkayastha, Sudarshana; Cai, Dongsheng

    2013-10-05

    Inflammatory reaction is a fundamental defense mechanism against threat towards normal integrity and physiology. On the other hand, chronic diseases such as obesity, type 2 diabetes, hypertension and atherosclerosis, have been causally linked to chronic, low-grade inflammation in various metabolic tissues. Recent cross-disciplinary research has led to identification of hypothalamic inflammatory changes that are triggered by overnutrition, orchestrated by hypothalamic immune system, and sustained through metabolic syndrome-associated pathophysiology. While continuing research is actively trying to underpin the identity and mechanisms of these inflammatory stimuli and actions involved in metabolic syndrome disorders and related diseases, proinflammatory IκB kinase-β (IKKβ), the downstream nuclear transcription factor NF-κB and some related molecules in the hypothalamus were discovered to be pathogenically significant. This article is to summarize recent progresses in the field of neuroendocrine research addressing the central integrative role of neuroinflammation in metabolic syndrome components ranging from obesity, glucose intolerance to cardiovascular dysfunctions.

  17. Metabolic Resistance in Bed Bugs

    Directory of Open Access Journals (Sweden)

    Omprakash Mittapalli

    2011-03-01

    Full Text Available Blood-feeding insects have evolved resistance to various insecticides (organochlorines, pyrethroids, carbamates, etc. through gene mutations and increased metabolism. Bed bugs (Cimex lectularius are hematophagous ectoparasites that are poised to become one of the major pests in households throughout the United States. Currently, C. lectularius has attained a high global impact status due to its sudden and rampant resurgence. Resistance to pesticides is one factor implicated in this phenomenon. Although much emphasis has been placed on target sensitivity, little to no knowledge is available on the role of key metabolic players (e.g., cytochrome P450s and glutathione S-transferases towards pesticide resistance in C. lectularius. In this review, we discuss different modes of resistance (target sensitivity, penetration resistance, behavioral resistance, and metabolic resistance with more emphasis on metabolic resistance.

  18. Exercise training in metabolic myopathies

    DEFF Research Database (Denmark)

    Vissing, J

    2016-01-01

    metabolic adaptations, such as increased dependence on glycogen use and a reduced capacity for fatty acid oxidation, which is detrimental in GSDs. Training has not been studied systematically in any FAODs and in just a few GSDs. However, studies on single bouts of exercise in most metabolic myopathies show......Metabolic myopathies encompass muscle glycogenoses (GSD) and disorders of muscle fat oxidation (FAOD). FAODs and GSDs can be divided into two main clinical phenotypes; those with static symptoms related to fixed muscle weakness and atrophy, and those with dynamic, exercise-related symptoms...... that are brought about by a deficient supply of ATP. Together with mitochondrial myopathies, metabolic myopathies are unique among muscle diseases, as the limitation in exercise performance is not solely caused by structural damage of muscle, but also or exclusively related to energy deficiency. ATP consumption...

  19. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  20. Metabolic pancreatitis: Etiopathogenesis and management

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2013-01-01

    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  1. B-12 vitamin metabolism disorders

    International Nuclear Information System (INIS)

    Fabriciova, K.; Bzduch, V.; Behulova, D.; Skodova, J.; Holesova, D.; Ostrozlikova, M.; Schmidtova, K.; Kozich, V.

    2012-01-01

    Vitamin B-12 – cobalamin (Cbl) is a water soluble vitamin, which is synthesized by lower organisms. It cannot be synthesized by plants and higher organisms. Problem in the metabolic pathway of Cbl can be caused by its deficiency or by the deficiency of its last metabolites – adenosylcobalamin and methylcobalamin. Both reasons are presented by errors in the homocysteine and methylmalonyl-coenzyme A metabolism. Clinical symptoms of the Cbl metabolism disorders are: different neurological disorders, changes in haematological status (megaloblastic anemia, pancytopenia), symptoms of gastrointestinal tract (glossitis, loss of appetite, diarrhea) and changes in the immune system. In the article the authors describe the causes of Cbl metabolism disorders, its different diagnosis and treatment. They introduce the group of patients with these disorders, who were taken care of in the I st Paediatric Department of University Children Hospital for the last 5 years. (author)

  2. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    Human Drug Metabolism, An Introduction, Second Edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences...

  3. Metabolic Effects of Ketogenic Diets

    OpenAIRE

    J Gordon Millichap

    1989-01-01

    The results of 24 metabolic profiles performed on 55 epileptic children receiving the classical ketogenic diet, the MCT diet, a modified MCT diet, and normal diets are reported from the University Department of Paediatrics, John Radcliffe Hospital, Oxford, England.

  4. Comprehensive and accurate tracking of carbon origin of LC-tandem mass spectrometry collisional fragments for 13C-MFA.

    Science.gov (United States)

    Kappelmann, Jannick; Klein, Bianca; Geilenkirchen, Petra; Noack, Stephan

    2017-03-01

    In recent years the benefit of measuring positionally resolved 13 C-labeling enrichment from tandem mass spectrometry (MS/MS) collisional fragments for improved precision of 13 C-Metabolic Flux Analysis ( 13 C-MFA) has become evident. However, the usage of positional labeling information for 13 C-MFA faces two challenges: (1) The mass spectrometric acquisition of a large number of potentially interfering mass transitions may hamper accuracy and sensitivity. (2) The positional identity of carbon atoms of product ions needs to be known. The present contribution addresses the latter challenge by deducing the maximal positional labeling information contained in LC-ESI-MS/MS spectra of product anions of central metabolism as well as product cations of amino acids. For this purpose, we draw on accurate mass spectrometry, selectively labeled standards, and published fragmentation pathways to structurally annotate all dominant mass peaks of a large collection of metabolites, some of which with a complete fragmentation pathway. Compiling all available information, we arrive at the most detailed map of carbon atom fate of LC-ESI-MS/MS collisional fragments yet, comprising 170 intense and structurally annotated product ions with unique carbon origin from 76 precursor ions of 72 metabolites. Our 13 C-data proof that heuristic fragmentation rules often fail to yield correct fragment structures and we expose common pitfalls in the structural annotation of product ions. We show that the positionally resolved 13 C-label information contained in the product ions that we structurally annotated allows to infer the entire isotopomer distribution of several central metabolism intermediates, which is experimentally demonstrated for malate using quadrupole-time-of-flight MS technology. Finally, the inclusion of the label information from a subset of these fragments improves flux precision in a Corynebacterium glutamicum model of the central carbon metabolism.

  5. [Endocrinological diseases, metabolic diseases, sexuality].

    Science.gov (United States)

    Lemaire, Antoine

    2014-10-01

    Sexuality is regularly evaluated in media surveys. Relations between sexual problems and some chronic pathologies as diabetes or metabolic syndrome have been brought to light. Androgen deficiency in the aging male has become a topic of increasing interest. Hormones play an important role in sexual function and relation between hormonal status and metabolic data are now well established. Copyright © 2014. Published by Elsevier Masson SAS.

  6. Evolution of metabolic network organization

    Directory of Open Access Journals (Sweden)

    Bonchev Danail

    2010-05-01

    Full Text Available Abstract Background Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints. Results We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya, from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints. Conclusions Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules

  7. Energy metabolism in the liver.

    Science.gov (United States)

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

  8. Drug treatment of metabolic syndrome.

    Science.gov (United States)

    Altabas, Velimir

    2013-08-01

    The metabolic syndrome is a constellation of risk factors for cardiovascular diseases including: abdominal obesity, a decreased ability to metabolize glucose (increased blood glucose levels and/or presence of insulin resistance), dyslipidemia, and hypertension. Patients who have developed this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Genetic factors and the environment both are important in the development of the metabolic syndrome, influencing all single components of this syndrome. The goals of therapy are to treat the underlying cause of the syndrome, to reduce morbidity, and to prevent complications, including premature death. Lifestyle modification is the preferred first-step treatment of the metabolic syndrome. There is no single effective drug treatment affecting all components of the syndrome equally known yet. However, each component of metabolic syndrome has independent goals to be achieved, so miscellaneous types of drugs are used in the treatment of this syndrome, including weight losing drugs, antidiabetics, antihypertensives, antilipemic and anticlothing drugs etc. This article provides a brief insight into contemporary drug treatment of components the metabolic syndrome.

  9. Epilepsy and astrocyte energy metabolism.

    Science.gov (United States)

    Boison, Detlev; Steinhäuser, Christian

    2018-06-01

    Epilepsy is a complex neurological syndrome characterized by neuronal hyperexcitability and sudden, synchronized electrical discharges that can manifest as seizures. It is now increasingly recognized that impaired astrocyte function and energy homeostasis play key roles in the pathogenesis of epilepsy. Excessive neuronal discharges can only happen, if adequate energy sources are made available to neurons. Conversely, energy depletion during seizures is an endogenous mechanism of seizure termination. Astrocytes control neuronal energy homeostasis through neurometabolic coupling. In this review, we will discuss how astrocyte dysfunction in epilepsy leads to distortion of key metabolic and biochemical mechanisms. Dysfunctional glutamate metabolism in astrocytes can directly contribute to neuronal hyperexcitability. Closure of astrocyte intercellular gap junction coupling as observed early during epileptogenesis limits activity-dependent trafficking of energy metabolites, but also impairs clearance of the extracellular space from accumulation of K + and glutamate. Dysfunctional astrocytes also increase the metabolism of adenosine, a metabolic product of ATP degradation that broadly inhibits energy-consuming processes as an evolutionary adaptation to conserve energy. Due to the critical role of astroglial energy homeostasis in the control of neuronal excitability, metabolic therapeutic approaches that prevent the utilization of glucose might represent a potent antiepileptic strategy. In particular, high fat low carbohydrate "ketogenic diets" as well as inhibitors of glycolysis and lactate metabolism are of growing interest for the therapy of epilepsy. © 2017 Wiley Periodicals, Inc.

  10. Metabolic syndrome and cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Abdullah M Alshehri

    2010-01-01

    Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

  11. Metabolic syndrome and cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Abdullah M Alshehri

    2010-11-01

    Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

  12. Symptoms and Diagnosis of Metabolic Syndrome

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More Symptoms and Diagnosis of Metabolic Syndrome Updated:Apr 13,2017 What are the symptoms ... Syndrome? This content was last reviewed August 2016. Metabolic Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • ...

  13. Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics

    OpenAIRE

    Cha, Ji-Young; Lee, Ho-Jae

    2016-01-01

    Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells c...

  14. Engineered coryneform bacteria as a bio-tool for arsenic remediation.

    Science.gov (United States)

    Villadangos, Almudena F; Ordóñez, Efrén; Pedre, Brandán; Messens, Joris; Gil, Jose A; Mateos, Luis M

    2014-12-01

    Despite current remediation efforts, arsenic contamination in water sources is still a major health problem, highlighting the need for new approaches. In this work, strains of the nonpathogenic and highly arsenic-resistant bacterium Corynebacterium glutamicum were used as inexpensive tools to accumulate inorganic arsenic, either as arsenate (As(V)) or arsenite (As(III)) species. The assays made use of "resting cells" from these strains, which were assessed under well-established conditions and compared with C. glutamicum background controls. The two mutant As(V)-accumulating strains were those used in a previously published study: (i) ArsC1/C2, in which the gene/s encoding the mycothiol-dependent arsenate reductases is/are disrupted, and (ii) MshA/C mutants unable to produce mycothiol, the low molecular weight thiol essential for arsenate reduction. The As(III)-accumulating strains were either those lacking the arsenite permease activities (Acr3-1 and Acr3-2) needed in As(III) release or recombinant strains overexpressing the aquaglyceroporin genes (glpF) from Corynebacterium diphtheriae or Streptomyces coelicolor, to improve As(III) uptake. Both genetically modified strains accumulated 30-fold more As(V) and 15-fold more As(III) than the controls. The arsenic resistance of the modified strains was inversely proportional to their metal accumulation ability. Our results provide the basis for investigations into the use of these modified C. glutamicum strains as a new bio-tool in arsenic remediation efforts.

  15. Metabolic Profiles of Brain Metastases

    Directory of Open Access Journals (Sweden)

    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  16. Energy Metabolism Impairment in Migraine.

    Science.gov (United States)

    Cevoli, Sabina; Favoni, Valentina; Cortelli, Pietro

    2018-06-22

    Migraine is a common disabling neurological disorder which is characterised by recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold create metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Insights into Brain Glycogen Metabolism

    Science.gov (United States)

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  18. Autophagic pathways and metabolic stress.

    Science.gov (United States)

    Kaushik, S; Singh, R; Cuervo, A M

    2010-10-01

    Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress has gained considerable attention. In this review, we focus on the novel findings linking autophagic function with metabolic stress resulting either from proteins or lipids. Proper autophagic activity is required in the cellular defense against proteotoxicity arising in the cytosol and also in the endoplasmic reticulum, where a vast amount of proteins are synthesized and folded. In addition, autophagy contributes to mobilization of intracellular lipid stores and may be central to lipid metabolism in certain cellular conditions. In this review, we focus on the interrelation between autophagy and different types of metabolic stress, specifically the stress resulting from the presence of misbehaving proteins within the cytosol or in the endoplasmic reticulum and the stress following a lipogenic challenge. We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders. © 2010 Blackwell Publishing Ltd.

  19. Gut microbiota and metabolic syndrome.

    Science.gov (United States)

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-11-21

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

  20. DNA methylation in metabolic disorders

    DEFF Research Database (Denmark)

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

  1. Metabolism and dosimetry of tritium

    International Nuclear Information System (INIS)

    Hill, R.L.; Johnson, J.R.

    1993-01-01

    This document was prepared as a review of the current knowledge of tritium metabolism and dosimetry. The physical, chemical, and metabolic characteristics of various forms of tritium are presented as they pertain to performing dose assessments for occupational workers and for the general public. For occupational workers, the forms of tritium discussed include tritiated water, elemental tritium gas, skin absorption from elemental tritium gas-contaminated surfaces, organically bound tritium in pump oils, solvents and other organic compounds, metal tritides, and radioluminous paints. For the general public, age-dependent tritium metabolism is reviewed, as well as tritiated water, elemental tritium gas, organically bound tritium, organically bound tritium in food-stuffs, and tritiated methane. 106 refs

  2. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  3. Flux networks in metabolic graphs

    International Nuclear Information System (INIS)

    Warren, P B; Queiros, S M Duarte; Jones, J L

    2009-01-01

    A metabolic model can be represented as a bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualization of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for other organisms

  4. 'Biomoleculas': cellular metabolism didactic software

    International Nuclear Information System (INIS)

    Menghi, M L; Novella, L P; Siebenlist, M R

    2007-01-01

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  5. Serotonin metabolism in rat brain

    International Nuclear Information System (INIS)

    Schutte, H.H.

    1976-01-01

    The metabolism of serotonin in rat brain was studied by measuring specific activities of tryptophan in plasma and of serotonin, 5-hydroxyindole acetic acid and tryptophan in the brain after intravenous injection of tritiated tryptophan. For a detailed analysis of the specific activities, a computer simulation technique was used. It was found that only a minor part of serotonin in rat brain is synthesized from tryptophan rapidly transported from the blood. It is suggested that the brain tryptophan originates from brain proteins. It was also found that the serotonin in rat brain is divided into more than one metabolic compartment

  6. Incidence and Major Metabolic Risk Factors of Metabolic Syndrome ...

    African Journals Online (AJOL)

    The study involved 300 (92 males and 208 females) type 2 diabetic patients and was conducted at the Tamale Teaching/Regional Hospital from June 2006 to May 2007. Metabolic syndrome was diagnosed using the National Cholesterol Education Programme, Adult Treatment Panel III (2001) criteria. The incidence of the ...

  7. Substrate metabolism in the metabolic response to injury

    NARCIS (Netherlands)

    Romijn, J. A.

    2000-01-01

    In healthy subjects the metabolic response to starvation invokes regulatory mechanisms aimed at conservation of protein mass. This response is characterized by a decrease in energy expenditure and a progressive decrease in urinary N excretion. Many non-endocrine diseases induce anorexia and a

  8. Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

    Science.gov (United States)

    Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

    2007-04-01

    Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic

  9. Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Anja Karlstaedt

    2018-06-01

    Full Text Available Recent advances in cancer cell metabolism provide unprecedented opportunities for a new understanding of heart metabolism and may offer new approaches for the treatment of heart failure. Key questions driving the cancer field to understand how tumor cells reprogram metabolism and to benefit tumorigenesis are also applicable to the heart. Recent experimental and conceptual advances in cancer cell metabolism provide the cardiovascular field with the unique opportunity to target metabolism. This review compares cancer cell metabolism and cardiac metabolism with an emphasis on strategies of cellular adaptation, and how to exploit metabolic changes for therapeutic benefit.

  10. Metabolic engineering in methanotrophic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Kalyuzhnaya, MG; Puri, AW; Lidstrom, ME

    2015-05-01

    Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  11. Nutrition, Epigenetics, and Metabolic Syndrome

    OpenAIRE

    Wang, Junjun; Wu, Zhenlong; Li, Defa; Li, Ning; Dindot, Scott V.; Satterfield, M. Carey; Bazer, Fuller W.; Wu, Guoyao

    2012-01-01

    Significance: Epidemiological and animal studies have demonstrated a close link between maternal nutrition and chronic metabolic disease in children and adults. Compelling experimental results also indicate that adverse effects of intrauterine growth restriction on offspring can be carried forward to subsequent generations through covalent modifications of DNA and core histones. Recent Advances: DNA methylation is catalyzed by S-adenosylmethionine-dependent DNA methyltransferases. Methylation...

  12. Iodine metabolism and food needs

    International Nuclear Information System (INIS)

    Mornex, R.

    1992-01-01

    Iodine is an element that is necessary for the growth and mental development of a child and for the maintenance of the activity of all cells at all ages. In this article, the author recalls the iodine sources, its metabolism and the food needs and contributions

  13. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  14. Dithiobiuret metabolism in the rat

    International Nuclear Information System (INIS)

    Williams, K.D.; Porter, W.R.; Peterson, R.E.

    1982-01-01

    Our main objective was to describe the metabolism of dithiobiuret (DTB) in the adult, male rat. Based on the thin-layer chromatographic analysis of urine from animals treated with [ 14 C] or [ 35 S] labeled DTB, two pathways for metabolism are proposed. One pathway is reversible and involves the oxidation of DTB to thiuret and the reduction of thiuret back to DTB. The other pathway consists of the desulfurization of DTB to monothiobiuret. The liver appears to desulfurate DTB because DTB-derived [35S] was eliminated from the liver more rapidly than [ 14 C]. The liver was the only tissue where the elimination kinetics of [ 35 S] and [ 14 C] DTB were different. DTB-derived radioactivity in urine that co-chromatographed with DTB, monothiobiuret, thiuret and sulfate was quantitated along with that of three uncharacterized metabolites. The presence of these unknown metabolites suggests that DTB metabolism is complex. The present study is the first description of the metabolic fate of DTB in the rat and serves as a starting point for determining whether DTB neurotoxicity is caused by the parent compound or a metabolite

  15. Cancer Metabolism: A Modeling Perspective

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells...

  16. MicroRNAs in Metabolism

    DEFF Research Database (Denmark)

    Vienberg, Sara; Geiger, Julian; Madsen, Søren

    2017-01-01

    roles in cholesterol and lipid metabolism, whereas miR-103 and -107 regulates hepatic insulin sensitivity. In muscle tissue a defined number of miRNAs (miR-1, miR-133, mir-206) control myofiber type switch and induce myogenic differentiation programs. Similarly, in adipose tissue a defined number of mi...

  17. Bile Acid Metabolism and Signaling

    Science.gov (United States)

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  18. Absorption and Metabolism of Xanthophylls

    Directory of Open Access Journals (Sweden)

    Eiichi Kotake-Nara

    2011-06-01

    Full Text Available Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  19. Absorption and metabolism of xanthophylls.

    Science.gov (United States)

    Kotake-Nara, Eiichi; Nagao, Akihiko

    2011-01-01

    Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  20. Modifying factors for metabolic parameters

    International Nuclear Information System (INIS)

    Inaba, Jiro

    1990-01-01

    Studies on factors which influence the metabolic parameter for calculation of radiation doses from intakes of radionuclides are very important for estimation of the doses for the general public, because the present procedures recommended by the International Commission on Radiological Protection is for occupationally exposed workers and the underlying metabolic and dosimetric models have been developed from studies on adult man and experiments on adult animals and from observations on radionuclides in physico-chemically simple form. Many factors have been reported to influence the metabolic parameters. Among them, the food-chain involvement of radionuclides and the age-dependence in humans and animals are most significant as environmental and physiological factor, respectively. In connection with the age-dependence of dose calculation, the ICRP started a new programme. They organized a Task Group on Age-Dependent Dose-Factors where relevant information on metabolic and biokinetic parameters are presently being reviewed for development of a set of dose factors for the following age-groups: infant, 1-year-old, 5-year-old, 10-year-old, 15-year-old, and ICRP Reference Man. The first stage of the work is for age-dependent integrated organ and effective dose factors for radioisotopes of the following elements: hydrogen, carbon, iodine, cesium, strontium, plutonium and americium. (author)

  1. SIRT1 and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Katarzyna Mac-Marcjanek

    2011-04-01

    Full Text Available Both obesity and type 2 diabetes mellitus, two major components of metabolic syndrome, become healthepidemics in the world. Over the past decade, advances in understanding the role of some regulators participatingin lipid and carbohydrate homeostasis have been made.Of them, SIRT1, the mammalian orthologue of the yeast Sir2 protein has been identified. SIRT1 is a nuclearNAD+-dependent deacetylase that targets many transcriptional modulators, including PPAR-α and -γ (peroxisomeproliferator-activated receptors α and γ, PGC-1α (PPAR-γ coactivator-1α, FOXO (forkhead box O proteins,and nuclear factor κB (NF-κB, thereby this enzyme mediates a wide range of physiological processes like apoptosis,fat metabolism, glucose homeostasis, and neurodegeneration.In this article, we discuss how SIRT1 regulates lipid and carbohydrate metabolism, and insulin secretion indifferent metabolic organs/tissue, including liver, muscle, pancreas, and fat. Additionally, the role of this enzymein reduction of inflammatory signalling is highlighted.

  2. Metabolism of phthalates in humans

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Skakkebaek, Niels E; Andersson, Anna-Maria

    2007-01-01

    on the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to phthalates via maternal exposure is a matter of concern. The metabolic pathways of phthalate metabolites excreted in human urine are partly known for some...

  3. Bone scintigraphy and metabolic disorders

    International Nuclear Information System (INIS)

    Mari', C.; Catafau, A.; Carrio', I.

    1999-01-01

    The paper discusses the main clinical value of bone scan in metabolic bone disease: its detection of focal conditions or focal complications of such generalized disease, its most common use of being the detection of fractures in osteoporosis, pseudofractures in osteomalacia and the evaluation of Paget's disease

  4. Bone scintigraphy and metabolic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Mari' , C.; Catafau, A.; Carrio' , I. [Hospital de Sant Pau, Barcelone (Spain). Serv. of Nuclear Medicine

    1999-09-01

    The paper discusses the main clinical value of bone scan in metabolic bone disease: its detection of focal conditions or focal complications of such generalized disease, its most common use of being the detection of fractures in osteoporosis, pseudo fractures in osteomalacia and the evaluation of Paget's disease.

  5. Use of ionizing radiation in the regulation of amino acid synthesis of micro organisms. Part of a coordinated programme on radiation microbiology

    International Nuclear Information System (INIS)

    Hall, A.N.

    1976-05-01

    The effects of ionizing radiations on the production of glutamic acid (from glucose) by Corynebacterium glutamicum was investigated. Experiments were carried out with resting cell systems and with growing cultures of C. glutamicum. The growing cultures produced optimum yields of glutamic acid (25-30% of theoretical) in culture medium containing 1,0μg/l of biotin. The yield was virtually zero when 25μg/l of biotin was supplied. Resting cells from a medium containing growth-limiting concentrations of biotin (1μg/l) gave good yield of glutamic acid (approximately 27%), while cells harvested from a biotin-rich medium produced only traces of glutamate. Pre-irradiated cells of C. glutamicum produced less glutamic acid than unirradiated cells, and continuously irradiated (3,03 and 4,76 rad/h resting cells accumulated less glutamic acid than the corresponding unirradiated controls. Considerable increase in the glutamate produced by C. glutamicum during growth in the presence of 25μg/l of biotin was induced by continuously irradiating the cultures from the time of inoculation. The increases in the actual concentration of glutamate and in the precentage yield vary from approximately 2-fold to 4-fold. A dose rate of 4.0 krad/h was the most effective of the ones tested

  6. Quantification of patterns of regional cardiac metabolism

    International Nuclear Information System (INIS)

    Lear, J.L.; Ackermann, R.F.

    1990-01-01

    To quantitatively map and compare patterns of regional cardiac metabolism with greater spatial resolution than is possible with positron emission tomography (PET), the authors developed autoradiographic techniques for use with combinations of radiolabeled fluorodeoxyglucose (FDG), glucose (GLU), and acetate (ACE) and applied the techniques to normal rats. Kinetic models were developed to compare GLU-based oxidative glucose metabolism with FDG-based total glucose metabolism (oxidative plus anaerobic) and to compare ACE-based overall oxidative metabolism with FDG-based total glucose metabolism. GLU-based metabolism generally paralleled FDG-based metabolism, but divergence occurred in certain structures such as the papillary muscles, where FDG-based metabolism was much greater. ACE-based metabolism also generally paralleled FDG-based metabolism, but again, the papillary muscles had relatively greater FDG-based metabolism. These discrepancies between FDG-based metabolism and GLU- or ACE-based metabolism suggest the presence of high levels of anaerobic glycolysis. Thus, the study indicates that anaerobic glycolysis, in addition to occurring in ischemic or stunned myocardium (as has been shown in recent PET studies), occurs normally in specific cardiac regions, despite the presence of abundant oxygen

  7. Albumin metabolism in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Kirsch, R E; Saunders, S J; Brock, J F [Cape Town Univ. (South Africa). Dept. of Medicine

    1979-11-24

    Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed.

  8. Fifteen years experience: Egyptian metabolic lab

    African Journals Online (AJOL)

    Ekram M. Fateen

    2014-08-20

    Aug 20, 2014 ... defective enzymes or transport proteins which results in a block of the metabolic pathway and accumulation ... The detection of metabolic disorder is done ..... [42] Wood TC, Harvey K, Beck M, Burin MG, Chien YH, Church HJ,.

  9. Albumin metabolism in health and disease

    International Nuclear Information System (INIS)

    Kirsch, R.E.; Saunders, S.J.; Brock, J.F.

    1979-01-01

    Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed

  10. Modelling of the metabolism of Zymomonas mobilis

    Energy Technology Data Exchange (ETDEWEB)

    Posten, C; Thoma, M

    1986-01-01

    In order to optimize fermentations with respect to media, reactor configuration, and control a structured model of the metabolism of Zymononas mobilis has been developed. The model is based on structure of metabolism, rate limiting steps, energy balance and metabolic elemental balances. A three-fold effect of ethanol has been observed concerning substrate-turnover, ammonia uptake and energy consumption. In addition to the metabolic view a structured cell-membrane-model should be considered.

  11. Cancer Cell Metabolism: One Hallmark, Many Faces

    OpenAIRE

    Cantor, Jason R.; Sabatini, David M.

    2012-01-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such chang...

  12. Phosphoinositide metabolism and metabolism-contraction coupling in rabbit aorta

    International Nuclear Information System (INIS)

    Coburn, R.F.; Baron, C.; Papadopoulos, M.T.

    1988-01-01

    The authors tested a hypothesis that metabolism-contraction coupling in vascular smooth muscle is controlled by the rate of delivery of energy to ATP-dependent reactions in the inositol phospholipid transduction system that generate second messengers exerting control on smooth muscle force. Rabbit aorta was contracted by norepinephrine (NOR) under conditions of normoxia and hypoxia, and changes in inositol phospholipid pool sizes and metabolic flux rates (J F ) were determined. J F was determined by labeling free cytosolic myo-inositol by incubation of unstimulated muscle with myo-[ 3 H]inositol and then measuring rates of incorporation of this isotope into inositol phospholipids and inositol phosphates when the muscle was activated by NOR. J F measured during maintenance of NOR-induced force was markedly inhibited during hypoxia to 40-50% of that determined during normoxia; rates of increases in inositol phosphate radioactivities were similarly depressed during NOR activation under hypoxia. The hypoxia-induced decrease in J F was associated with four- to fivefold increase in phosphatidylinositol 4-phosphate (PIP) total pool size, suggesting PIP kinase was inhibited and rate limiting. These data suggest that activation of inositol phospholipid metabolism, which generates inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol, is blunted under conditions where aerobic energy production is inhibited. Data are consistent with rate-limiting effects of decreased ATP delivery, or decreased phosphate potential, on PIP kinase and reactions that control resynthesis of phosphatidylinositol

  13. It must be my metabolism: Metabolic control of mind

    Directory of Open Access Journals (Sweden)

    Dana M Small

    2014-07-01

    relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

  14. Metabolic markers in sports medicine.

    Science.gov (United States)

    Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

    2012-01-01

    Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should

  15. The metabolic syndrome among Danish seafarers

    DEFF Research Database (Denmark)

    Jepsen, Jørgen Riis; Rasmussen, Hanna Barbara

    2016-01-01

    Background: The metabolic syndrome (MS) represents a cluster of risk factors related to insulin resistance. Metabolic syndrome is a strong risk factor for chronic metabolic and cardiovascular diseases and is related to nutritional factors, sleep patterns, work-related stress, fatigue, and physical...

  16. Intestinal metabolism of sulfur amino acids

    Science.gov (United States)

    The gastrointestinal tract (GIT) is a metabolically significant site of sulfur amino acid (SAA) metabolism in the body and metabolizes approx. 20% of the dietary methionine intake that is mainly transmethylated to homocysteine and transsulfurated to cysteine. The GIT accounts for approx. 25% of the ...

  17. Understanding Regulation of Metabolism through Feasibility Analysis

    NARCIS (Netherlands)

    Nikerel, I.E.; Berkhout, J.; Hu, F.; Teusink, B.; Reinders, M.J.T.; De Ridder, D.

    2012-01-01

    Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but

  18. Urban metabolism: A review of research methodologies

    International Nuclear Information System (INIS)

    Zhang, Yan

    2013-01-01

    Urban metabolism analysis has become an important tool for the study of urban ecosystems. The problems of large metabolic throughput, low metabolic efficiency, and disordered metabolic processes are a major cause of unhealthy urban systems. In this paper, I summarize the international research on urban metabolism, and describe the progress that has been made in terms of research methodologies. I also review the methods used in accounting for and evaluating material and energy flows in urban metabolic processes, simulation of these flows using a network model, and practical applications of these methods. Based on this review of the literature, I propose directions for future research, and particularly the need to study the urban carbon metabolism because of the modern context of global climate change. Moreover, I recommend more research on the optimal regulation of urban metabolic systems. Highlights: •Urban metabolic processes can be analyzed by regarding cities as superorganisms. •Urban metabolism methods include accounting, assessment, modeling, and regulation. •Research methodologies have improved greatly since this field began in 1965. •Future research should focus on carbon metabolism and optimal regulation. -- The author reviews research progress in the field of urban metabolism, and based on her literature review, proposes directions for future research

  19. Use of sugar cane molasses and vinasse for proteic and lipidic biomass production by yeast and bacteria

    Directory of Open Access Journals (Sweden)

    Marcia Luciana Cazetta

    2005-02-01

    Full Text Available This work evaluated the lipid and protein growth and synthesis capacity by Saccharomyces cerevisiae, Rhodotoruda mucilaginosa, Candida lipolytica, a yeast isolated from vinasse lakes and Corynebacterium glutamicum in 10% molasses and sugar cane crude vinasse. All microorganisms grew both in molasses and vinasse. The highest growth in crude vinasse was performed by R. mucilaginosa (7.05 g/L, and in 10% molasses, by C. lipolytica, yielding 6,09 g/L. In vinasse, the highest protein content in the biomass was produced by S. cerevisiae (50.35% and in 10% molasses, by C. glutamicum (46,16%. C. lipolytica and R. mucilaginosa showed the best lipid production, above 20% and 18%, respectively, both in vinasse and in molasses.

  20. Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*

    Science.gov (United States)

    Xu, Jian-zhong; Zhang, Wei-guo

    2016-01-01

    With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID:26834010

  1. Metabolic Effects of Intermittent Fasting.

    Science.gov (United States)

    Patterson, Ruth E; Sears, Dorothy D

    2017-08-21

    The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

  2. Metabolism of phthalates in humans

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Skakkebaek, Niels E; Andersson, Anna-Maria

    2007-01-01

    on the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to phthalates via maternal exposure is a matter of concern. The metabolic pathways of phthalate metabolites excreted in human urine are partly known for some...... phthalates, but our knowledge about metabolic distribution in the body and other biological fluids, including breast milk, is limited. Compared to urine, human breast milk contains relatively more of the hydrophobic phthalates, such as di-n-butyl phthalate and the longer-branched, di(2-ethylhexyl) phthalate...... (DEHP) and di-iso-nonyl phthalate (DiNP); and their monoester metabolites. Urine, however, contains relatively more of the secondary metabolites of DEHP and DiNP, as well as the monoester phthalates of the more short-branched phthalates. This differential distribution is of special concern as...

  3. PET Metabolic Biomarkers for Cancer

    Directory of Open Access Journals (Sweden)

    Etienne Croteau

    2016-01-01

    Full Text Available The body's main fuel sources are fats, carbohydrates (glucose, proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET imaging using the glucose analog 18 F-fluorodeoxyglucose ( 18 F-FDG has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

  4. [FETAL PROGRAMMING OF METABOLIC DISORDERS].

    Science.gov (United States)

    Varadinova, M R; Metodieva, R; Boyadzhieva, N

    2015-01-01

    Our knowledge of fetal programming has developed notably over the years and recent data suggest that an unbalanced diet prior and during pregnancy can have early-onset and long-lasting consequences on the health of the offspring. Specific negative influences of high dietary glucose and lipid consumption, as well as undernutrition, are associated with development of metabolic syndrome, insulin resistance and diabetes in the offspring. The mechanisms underlying the effects of maternal hyperglycemia on the fetus may involve structural, metabolic and epigenetic changes. The aim of this review is to illustrate how adverse intrauterine environment may influence molecular modifications in the fetus and cause epigenetic alterations in particular. It has been demonstrated that prenatal epigenetic modifications may be linked to the pathogenesis and progression of the adult chronic disorders. Studies on epigenetic alterations will contribute to a better understanding of the long-term effects of in utero exposure and may open new perspectives for disease prevention and treatment.

  5. Carbohydrate metabolism in Bacillus subtilis

    International Nuclear Information System (INIS)

    Riedel, K.

    1980-01-01

    The glucose metabolism via the glycolytic pathway as well as via the oxidative and inoxidative hexose monophosphate pathways in Bacillus subtilis was studied applying 1- 14 C- and 6- 14 C-glucose, respectively, and determining labelled CO 2 and RNA. A method for calculating the catabolic pathways was developed. In nonproliferating cultures glucose is catabolized to 62% via the glycolytic pathway, to 20% via the oxidative, and to 18% via the inoxidative pathway

  6. Renal Ammonia Metabolism and Transport

    Science.gov (United States)

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  7. The Metabolic Basis of Cystinosis

    Science.gov (United States)

    1981-05-12

    glucose, amino acids and other organic acids appear. The present- ing symptoms of the disease— polyuria , polydipsia and recurrent unexplained fevers are... polyuria and polydypsia which results make children with the disease extremely susceptible to dehydration. This vulnerability to dehydration explains...on the relations between renal rickets (renal dwarfism) and renal diabetes . In: Stanbury J.Wyngaarden J.B., Frederickson D.S., eds. The Metabolic

  8. The cradle of metabolic disease

    OpenAIRE

    Galjaard, Sander

    2015-01-01

    Summary -Vascular development and FETAL body composition during pregnancy- The effects of maternal adiposity (high body mass index - high BMI -), nutrient intake and storage (gestational weight gain - GWG -) and (abnormal) glucose tolerance (gestational diabetes - GDM - ) are regarded important cornerstones in metabolic research in pregnancy. In Chapter 1, I explained, that they play an important role in the development of complications in the mother and the fetus, both short- and long-ter...

  9. Metabolic syndrome in Iranian elderly

    Directory of Open Access Journals (Sweden)

    Nizal Sarrafzadegan

    2012-01-01

    Full Text Available BACKGROUND: This study aimed to compare Iranian elderly with the youth and middle aged population in terms of the prevalence of metabolic syndrome and its components in Iranian elderly METHODS: This cross-sectional study was conducted using the information from the third phase of Isfahan Healthy Heart Program. Male and female residents of Isfahan who aged over 19 years were selected by multistage cluster random sampling. A questionnaire including demographic characteristics, health status, medical history, medications used, as well as waist circumference, weight, height and systolic and diastolic blood pressures was completed for all participants. Fasting blood samples were obtained from all subjects and examined for fasting blood sugar and lipid profile. RESULTS: The prevalence of metabolic syndrome in individuals aged over 60 years was significantly higher than those under 60 (49.5% vs. 17.5%, respectively; P < 0.001. It was also more prevalent among elderly females than in males (59.2% vs. 39.8%, respectively; P < 0.005. Some anthropometric measures such as height, body mass index, abdominal circumference, waist-hip ratio, and waist to height ratio were significantly different in men and women below 60 years in comparison with those over 60 years (P < 0.05. Moreover, there were significant differences in most studied parameters between the elderly and non-elderly women (P < 0.001. Based on the findings of this study, the risk factors for cardiovascular diseases were significantly more prevalent in men and women over 60 years. T-test and Mann-Whitney were used for quantitative data and the square-chi test is performed for qualitative data.    CONCLUSION: This study showed that metabolic syndrome has a relatively high prevalence in Iranian elderly people (especially in women. Therefore, early diagnosis and management of the complication are recommended among this high-risk group. Keywords: Metabolic Syndrome, Elderly, Iran

  10. The energy metabolism of megacities

    International Nuclear Information System (INIS)

    Facchini, Angelo; Kennedy, Chris; Stewart, Iain; Mele, Renata

    2017-01-01

    Highlights: • Energy metabolism leads to a better management of energy use in megacities. • Insights on strategies to improve energy efficiency and reduce resource consumption. • We find a regionalization of energy flows and sectoral energy use. • Scaling law for energy Vs density suggests strategies for compact cities planning. • Supports development of models to reduce GHG emissions and increase resilience. - Abstract: Due to their sheer size and complexity, megacities are extreme examples in which both negative and positive aspects of urbanization co-exist and are amplified. Especially in emerging countries they are becoming the dominant paradigm of the future urbanization, representing a sustainability challenge both from the point of view of energy and resource consumption, and from the point of view of climate change adaptation and mitigation. In this paper we compare the energy metabolism in 27 of the world’s megacities including details of mobile and stationary energy consumption patterns, fuels used, as well as end-use patterns and electricity generation mix. Our results show that per capita total energy consumption scales with urban population density according to a power law characterized by the universal −3/4 scaling, pointing out that compact cities are more energy efficient with respect to dispersed cities. By comparing energy sources and sectoral end use, also focusing on electricity use and generation source, we found a significant regionalization of energy metabolism, and we discuss the implication for resilience, infrastructure planning, GHG emissions, and policies for infrastructure decarbonization. The comparison of the energy metabolism can lead to a more appropriate management of energy use patterns and electricity generation mix in megacities, giving insights on strategies to improve urban energy efficiency and reducing environmental pressure of megacities.

  11. Bone Metabolism after Bariatric Surgery

    Science.gov (United States)

    Yu, Elaine W.

    2014-01-01

    Bariatric surgery is a popular and effective treatment for severe obesity, but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically-induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery. PMID:24677277

  12. Prisoner's dilemma in cancer metabolism.

    Directory of Open Access Journals (Sweden)

    Irina Kareva

    Full Text Available As tumors outgrow their blood supply and become oxygen deprived, they switch to less energetically efficient but oxygen-independent anaerobic glucose metabolism. However, cancer cells maintain glycolytic phenotype even in the areas of ample oxygen supply (Warburg effect. It has been hypothesized that the competitive advantage that glycolytic cells get over aerobic cells is achieved through secretion of lactic acid, which is a by-product of glycolysis. It creates acidic microenvironment around the tumor that can be toxic to normal somatic cells. This interaction can be seen as a prisoner's dilemma: from the point of view of metabolic payoffs, it is better for cells to cooperate and become better competitors but neither cell has an incentive to unilaterally change its metabolic strategy. In this paper a novel mathematical technique, which allows reducing an otherwise infinitely dimensional system to low dimensionality, is used to demonstrate that changing the environment can take the cells out of this equilibrium and that it is cooperation that can in fact lead to the cell population committing evolutionary suicide.

  13. Mitochondrial Metabolism in Aging Heart

    Science.gov (United States)

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  14. Genetic determinants of HDL metabolism.

    Science.gov (United States)

    Ossoli, A; Gomaraschi, M; Franceschini, G; Calabresi, L

    2014-01-01

    Plasma high density lipoproteins (HDL) comprise a highly heterogeneous family of lipoprotein particles, with subclasses that can be separated and identified according to density, size, surface charge as well as shape and protein composition. There is evidence that these subclasses may differ in their functional properties. The individual plasma HDL cholesterol (HDL-C) level is generally taken as a snapshot of the steady-state concentration of all circulating HDL subclasses together, but this is insufficient to capture the structural and functional variation in HDL particles. HDL are continuously remodeled and metabolized in plasma and interstitial fluids, through the interaction with a large number of factors, including structural proteins, membrane transporters, enzymes, transfer proteins and receptors. Genetic variation in these factors can lead to essential changes in plasma HDL levels, and to remarkable changes in HDL particle density, size, surface charge, shape, and composition in lipids and apolipoproteins. This review discusses the impact of rare mutations and common variants in genes encoding factors involved in HDL remodeling and metabolism on plasma HDL-C levels and particle distribution. The study of the effects of human genetic variation in major players in HDL metabolism provides important clues on how individual factors modulate the formation, maturation, remodeling and catabolism of HDL.

  15. Expression of a bacterial 3-dehydroshikimate dehydratase reduces lignin content and improves biomass saccharification efficiency.

    Science.gov (United States)

    Eudes, Aymerick; Sathitsuksanoh, Noppadon; Baidoo, Edward E K; George, Anthe; Liang, Yan; Yang, Fan; Singh, Seema; Keasling, Jay D; Simmons, Blake A; Loqué, Dominique

    2015-12-01

    Lignin confers recalcitrance to plant biomass used as feedstocks in agro-processing industries or as source of renewable sugars for the production of bioproducts. The metabolic steps for the synthesis of lignin building blocks belong to the shikimate and phenylpropanoid pathways. Genetic engineering efforts to reduce lignin content typically employ gene knockout or gene silencing techniques to constitutively repress one of these metabolic pathways. Recently, new strategies have emerged offering better spatiotemporal control of lignin deposition, including the expression of enzymes that interfere with the normal process for cell wall lignification. In this study, we report that expression of a 3-dehydroshikimate dehydratase (QsuB from Corynebacterium glutamicum) reduces lignin deposition in Arabidopsis cell walls. QsuB was targeted to the plastids to convert 3-dehydroshikimate - an intermediate of the shikimate pathway - into protocatechuate. Compared to wild-type plants, lines expressing QsuB contain higher amounts of protocatechuate, p-coumarate, p-coumaraldehyde and p-coumaryl alcohol, and lower amounts of coniferaldehyde, coniferyl alcohol, sinapaldehyde and sinapyl alcohol. 2D-NMR spectroscopy and pyrolysis-gas chromatography/mass spectrometry (pyro-GC/MS) reveal an increase of p-hydroxyphenyl units and a reduction of guaiacyl units in the lignin of QsuB lines. Size-exclusion chromatography indicates a lower degree of lignin polymerization in the transgenic lines. Therefore, our data show that the expression of QsuB primarily affects the lignin biosynthetic pathway. Finally, biomass from these lines exhibits more than a twofold improvement in saccharification efficiency. We conclude that the expression of QsuB in plants, in combination with specific promoters, is a promising gain-of-function strategy for spatiotemporal reduction of lignin in plant biomass. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The

  16. DNA Damage, Repair, and Cancer Metabolism

    Science.gov (United States)

    Turgeon, Marc-Olivier; Perry, Nicholas J. S.; Poulogiannis, George

    2018-01-01

    Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part