WorldWideScience

Sample records for natural products biosynthesis

  1. Benchmarking of Processes for the Biosynthesis of Natural Products

    DEFF Research Database (Denmark)

    Seita, Catarina Sanches

    putida GS1. (R)-perillic acid is a monoterpenoic acid with antimicrobial properties. It has a strong inhibitory effect on bacteria and fungus, which makes it an attractive compound to be used as a preservative for instance in cosmetic industry, but on the other hand makes the biosynthesis a complicated....... These biological activities can be of interest for use in different sectors of chemical industry, in particular pharmaceutical industry where several drugs are derived or inspired by natural products structure. However, the large scale production of natural products is hindered by its relatively poor abundance...... of the process in comparison with other sweeteners. The main benefit of this early-stage evaluation is putting the biosynthesis of natural products into context in relation to demands of an industrially feasible chemical process. Moreover, it can give very meaningful insight into process development and provides...

  2. Biosynthesis of therapeutic natural products using synthetic biology.

    Science.gov (United States)

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Rational synthetic pathway refactoring of natural products biosynthesis in actinobacteria.

    Science.gov (United States)

    Tan, Gao-Yi; Liu, Tiangang

    2017-01-01

    Natural products (NPs) and their derivatives are widely used as frontline treatments for many diseases. Actinobacteria spp. are used to produce most of NP antibiotics and have also been intensively investigated for NP production, derivatization, and discovery. However, due to the complicated transcriptional and metabolic regulation of NP biosynthesis in Actinobacteria, especially in the cases of genome mining and heterologous expression, it is often difficult to rationally and systematically engineer synthetic pathways to maximize biosynthetic efficiency. With the emergence of new tools and methods in metabolic engineering, the synthetic pathways of many chemicals, such as fatty acids and biofuels, in model organisms (e.g. Escherichia coli ), have been refactored to realize precise and flexible control of production. These studies also offer a promising approach for synthetic pathway refactoring in Actinobacteria. In this review, the great potential of Actinobacteria as a microbial cell factory for biosynthesis of NPs is discussed. To this end, recent progress in metabolic engineering of NP synthetic pathways in Actinobacteria are summarized and strategies and perspectives to rationally and systematically refactor synthetic pathways in Actinobacteria are highlighted. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Recent advances in the elucidation of enzymatic function in natural product biosynthesis [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Gao-Yi Tan

    2016-02-01

    Full Text Available With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.

  5. Recent advances in the elucidation of enzymatic function in natural product biosynthesis [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Tan Gao-Yi

    2015-12-01

    Full Text Available With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.

  6. Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis.

    Science.gov (United States)

    Wong, Fong T; Hotta, Kinya; Chen, Xi; Fang, Minyi; Watanabe, Kenji; Kim, Chu-Young

    2015-01-14

    Biosynthesis of some polyether natural products involves a kinetically disfavored epoxide-opening cyclic ether formation, a reaction termed anti-Baldwin cyclization. One such example is the biosynthesis of lasalocid A, an ionophore antibiotic polyether. During lasalocid A biosynthesis, an epoxide hydrolase, Lsd19, converts the bisepoxy polyketide intermediate into the tetrahydrofuranyl-tetrahydropyran product. We report the crystal structure of Lsd19 in complex with lasalocid A. The structure unambiguously shows that the C-terminal domain of Lsd19 catalyzes the intriguing anti-Baldwin cyclization. We propose a general mechanism for epoxide selection by ionophore polyether epoxide hydrolases.

  7. Flavin-catalyzed redox tailoring reactions in natural product biosynthesis.

    Science.gov (United States)

    Teufel, Robin

    2017-10-15

    Natural products are distinct and often highly complex organic molecules that constitute not only an important drug source, but have also pushed the field of organic chemistry by providing intricate targets for total synthesis. How the astonishing structural diversity of natural products is enzymatically generated in biosynthetic pathways remains a challenging research area, which requires detailed and sophisticated approaches to elucidate the underlying catalytic mechanisms. Commonly, the diversification of precursor molecules into distinct natural products relies on the action of pathway-specific tailoring enzymes that catalyze, e.g., acylations, glycosylations, or redox reactions. This review highlights a selection of tailoring enzymes that employ riboflavin (vitamin B2)-derived cofactors (FAD and FMN) to facilitate unusual redox catalysis and steer the formation of complex natural product pharmacophores. Remarkably, several such recently reported flavin-dependent tailoring enzymes expand the classical paradigms of flavin biochemistry leading, e.g., to the discovery of the flavin-N5-oxide - a novel flavin redox state and oxygenating species. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Rieske non-heme iron-dependent oxygenases catalyse diverse reactions in natural product biosynthesis.

    Science.gov (United States)

    Perry, Christopher; de Los Santos, Emmanuel L C; Alkhalaf, Lona M; Challis, Gregory L

    2018-04-13

    Covering: up to the end of 2017The roles played by Rieske non-heme iron-dependent oxygenases in natural product biosynthesis are reviewed, with particular focus on experimentally characterised examples. Enzymes belonging to this class are known to catalyse a range of transformations, including oxidative carbocyclisation, N-oxygenation, C-hydroxylation and C-C desaturation. Examples of such enzymes that have yet to be experimentally investigated are also briefly described and their likely functions are discussed.

  9. Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function.

    Science.gov (United States)

    Rudolf, Jeffrey D; Chang, Chin-Yuan; Ma, Ming; Shen, Ben

    2017-08-30

    Covering: up to January 2017Cytochrome P450 enzymes (P450s) are some of the most exquisite and versatile biocatalysts found in nature. In addition to their well-known roles in steroid biosynthesis and drug metabolism in humans, P450s are key players in natural product biosynthetic pathways. Natural products, the most chemically and structurally diverse small molecules known, require an extensive collection of P450s to accept and functionalize their unique scaffolds. In this review, we survey the current catalytic landscape of P450s within the Streptomyces genus, one of the most prolific producers of natural products, and comprehensively summarize the functionally characterized P450s from Streptomyces. A sequence similarity network of >8500 P450s revealed insights into the sequence-function relationships of these oxygen-dependent metalloenzymes. Although only ∼2.4% and structurally characterized, respectively, the study of streptomycete P450s involved in the biosynthesis of natural products has revealed their diverse roles in nature, expanded their catalytic repertoire, created structural and mechanistic paradigms, and exposed their potential for biomedical and biotechnological applications. Continued study of these remarkable enzymes will undoubtedly expose their true complement of chemical and biological capabilities.

  10. The Catalytic Diversity of Multimodular Polyketide Synthases: Natural Product Biosynthesis Beyond Textbook Assembly Rules.

    Science.gov (United States)

    Gulder, Tobias A M; Freeman, Michael F; Piel, Jörn

    2011-03-01

    Bacterial multimodular polyketide synthases (PKSs) are responsible for the biosynthesis of a wide range of pharmacologically active natural products. These megaenzymes contain numerous catalytic and structural domains and act as biochemical templates to generate complex polyketides in an assembly line-like fashion. While the prototypical PKS is composed of only a few different domain types that are fused together in a combinatorial fashion, an increasing number of enzymes is being found that contain additional components. These domains can introduce remarkably diverse modifications into polyketides. This review discusses our current understanding of such noncanonical domains and their role in expanding the biosynthetic versatility of bacterial PKSs.

  11. Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology.

    Science.gov (United States)

    Gogineni, Vedanjali; Hamann, Mark T

    2018-01-01

    The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources.

    Science.gov (United States)

    Ni, Jun; Tao, Fei; Du, Huaiqing; Xu, Ping

    2015-09-02

    Plant secondary metabolites have been attracting people's attention for centuries, due to their potentials; however, their production is still difficult and costly. The rich diversity of microbes and microbial genome sequence data provide unprecedented gene resources that enable to develop efficient artificial pathways in microorganisms. Here, by mimicking a natural pathway of plants using microbial genes, a new metabolic route was developed in E. coli for the synthesis of vanillin, the most widely used flavoring agent. A series of factors were systematically investigated for raising production, including efficiency and suitability of genes, gene dosage, and culture media. The metabolically engineered strain produced 97.2 mg/L vanillin from l-tyrosine, 19.3 mg/L from glucose, 13.3 mg/L from xylose and 24.7 mg/L from glycerol. These results show that the metabolic route enables production of natural vanillin from low-cost substrates, suggesting that it is a good strategy to mimick natural pathways for artificial pathway design.

  13. Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources

    Science.gov (United States)

    Ni, Jun; Tao, Fei; Du, Huaiqing; Xu, Ping

    2015-01-01

    Plant secondary metabolites have been attracting people’s attention for centuries, due to their potentials; however, their production is still difficult and costly. The rich diversity of microbes and microbial genome sequence data provide unprecedented gene resources that enable to develop efficient artificial pathways in microorganisms. Here, by mimicking a natural pathway of plants using microbial genes, a new metabolic route was developed in E. coli for the synthesis of vanillin, the most widely used flavoring agent. A series of factors were systematically investigated for raising production, including efficiency and suitability of genes, gene dosage, and culture media. The metabolically engineered strain produced 97.2 mg/L vanillin from l-tyrosine, 19.3 mg/L from glucose, 13.3 mg/L from xylose and 24.7 mg/L from glycerol. These results show that the metabolic route enables production of natural vanillin from low-cost substrates, suggesting that it is a good strategy to mimick natural pathways for artificial pathway design. PMID:26329726

  14. Substrate Scope of O-Methyltransferase from Streptomyces peucetius for Biosynthesis of Diverse Natural Products Methoxides.

    Science.gov (United States)

    Parajuli, Prakash; Pandey, Ramesh Prasad; Nguyen, Thi Huyen Trang; Dhakal, Dipesh; Sohng, Jae Kyung

    2018-04-01

    Methylation is a common post-modification reaction that is observed during the biosynthesis of secondary metabolites produced by plants and microorganisms. Based on the sequence information from Streptomyces peucetius ATCC27952, a putative O-methyltransferase (OMT) gene SpOMT7740 was polymerase chain reaction amplified and cloned into E. coli BL21 (DE3) host to test the substrate promiscuity and conduct functional characterization. In vitro and in vivo reaction assays were carried out over various classes of substrates: flavonoids (flavonol, flavones, and isoflavonoid), chalcones, anthraquinones, anthracyclines, and sterol molecules, and the applications in synthesizing diverse classes of O-methoxy natural products were also illustrated. SpOMT7740 catalyzed the O-methylation reaction to form various natural and non-natural O-methoxides, includes 7-hydroxy-8-O-methoxy flavone, 3-O-methoxy flavone, three mono-, di-, and tri-O-methoxy genistein, mono-O-methoxy phloretin, mono-O-methoxy luteolin, 3-O-methoxy β-sitosterol, and O-methoxy anthraquinones (emodin and aloe emodin) and O-methoxy anthracycline (daunorubicin) exhibiting diverse substrate flexibility. Daunorubicin is a native secondary metabolite of S. peucetius. Among the compounds tested, 7,8-dihydroxyflavone was the best substrate for bioconversion to 7-hydroxy-8-O-methoxy flavone, and it was structurally elucidated. This enzyme showed a flexible catalysis over the given ranges of temperature, pH, and divalent cationic conditions for O-methylation.

  15. Insights into natural products biosynthesis from analysis of 490 polyketide synthases from Fusarium.

    Science.gov (United States)

    Brown, Daren W; Proctor, Robert H

    2016-04-01

    Species of the fungus Fusarium collectively cause disease on almost all crop plants and produce numerous natural products (NPs), including some of the mycotoxins of greatest concern to agriculture. Many Fusarium NPs are derived from polyketide synthases (PKSs), large multi-domain enzymes that catalyze sequential condensation of simple carboxylic acids to form polyketides. To gain insight into the biosynthesis of polyketide-derived NPs in Fusarium, we retrieved 488 PKS gene sequences from genome sequences of 31 species of the fungus. In addition to these apparently functional PKS genes, the genomes collectively included 81 pseudogenized PKS genes. Phylogenetic analysis resolved the PKS genes into 67 clades, and based on multiple lines of evidence, we propose that homologs in each clade are responsible for synthesis of a polyketide that is distinct from those synthesized by PKSs in other clades. The presence and absence of PKS genes among the species examined indicated marked differences in distribution of PKS homologs. Comparisons of Fusarium PKS genes and genes flanking them to those from other Ascomycetes provided evidence that Fusarium has the genetic potential to synthesize multiple NPs that are the same or similar to those reported in other fungi, but that have not yet been reported in Fusarium. The results also highlight ways in which such analyses can help guide identification of novel Fusarium NPs and differences in NP biosynthetic capabilities that exist among fungi. Published by Elsevier Inc.

  16. Aspergillus nidulans Natural Product Biosynthesis Is Regulated by MpkB, a Putative Pheromone Response Mitogen-Activated Protein Kinase

    International Nuclear Information System (INIS)

    Atoui, A.; Bao, D.; Kaur, N.; Grayburn, W.S.; Calvo, A.M.

    2008-01-01

    The Aspergillus nidulans putative mitogen-activated protein kinase encoded by mpkB has a role in natural product biosynthesis. An mpkB mutant exhibited a decrease in sterigmatocystin gene expression and low mycotoxin levels. The mutation also affected the expression of genes involved in penicillin and terrequinone A synthesis. mpkB was necessary for normal expression of laeA, which has been found to regulate secondary metabolism gene clusters. (author)

  17. [Elaboration of Pseudo-natural Products Using Artificial In Vitro Biosynthesis Systems].

    Science.gov (United States)

    Goto, Yuki

    2018-01-01

     Peptidic natural products often consist of not only proteinogenic building blocks but also unique non-proteinogenic structures such as macrocyclic scaffolds and N-methylated backbones. Since such non-proteinogenic structures are important structural motifs that contribute to diverse bioactivity, we have proposed that peptides with non-proteinogenic structures should be attractive candidates as artificial bioactive peptides mimicking natural products, or so-called pseudo-natural products. We previously devised an engineered translation system for pseudo-natural peptides, referred to as the flexible in vitro translation (FIT) system. This system enabled "one-pot" synthesis of highly diverse pseudo-natural peptide libraries, which can be rapidly screened by mRNA display technology for the discovery of pseudo-natural peptides with diverse bioactivities.

  18. Direct capture and heterologous expression of Salinispora natural product genes for the biosynthesis of enterocin.

    Science.gov (United States)

    Bonet, Bailey; Teufel, Robin; Crüsemann, Max; Ziemert, Nadine; Moore, Bradley S

    2015-03-27

    Heterologous expression of secondary metabolic pathways is a promising approach for the discovery and characterization of bioactive natural products. Herein we report the first heterologous expression of a natural product from the model marine actinomycete genus Salinispora. Using the recently developed method of yeast-mediated transformation-associated recombination for natural product gene clusters, we captured a type II polyketide synthase pathway from Salinispora pacifica with high homology to the enterocin pathway from Streptomyces maritimus and successfully produced enterocin in two different Streptomyces host strains. This result paves the way for the systematic interrogation of Salinispora's promising secondary metabolome.

  19. Nuclear magnetic resonance spectroscopy in the structure elucidation and biosynthesis of natural products

    International Nuclear Information System (INIS)

    Meksuriyen, D.

    1988-01-01

    Examination of a chloroform extract of Dracaena loureiri Gagnep (Agavaceae), a Thia medicinal plant possessing antibacterial activity, has led to the isolation of fifteen flavenoids. The biogenic relationships among these flavenoids isolated were briefly discussed. Definition of the skeleton and the unambiguous assignment of all of the protons of the isolates was achieved through extensive 2D-homonuclear chemical shift correlation, nuclear Overhauser effect (NOE) difference spectroscopy and 2D-NOE experiments. The 1 H and 13 C NMR spectra of staurosporine, a potent biologically active agent from Streptomyces staurosporeus, were unambiguously assigned by using 2D homonuclear chemical shift correlation, NOE, 1 H-detected heteronuclear multiple-quantum coherence via direct coupling and via multiple-bond coupling for resonance assignments of protonated and nonprotonated carbons, respectively. S. Staurosporeus was found to utilize endogenous and exogenous D- and L-isomers of trytophan in the production of staurosporine. The biosynthesis of staurosporine was examined by employing carbon-14, tritium, and carbon-13 labeled precursors

  20. Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

    Directory of Open Access Journals (Sweden)

    Jens Schmidt

    2014-05-01

    Full Text Available The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423 in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products.

  1. SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis

    Science.gov (United States)

    Ohashi, Masao; Liu, Fang; Hai, Yang; Chen, Mengbin; Tang, Man-Cheng; Yang, Zhongyue; Sato, Michio; Watanabe, Kenji; Houk, K. N.; Tang, Yi

    2017-09-01

    Pericyclic reactions—which proceed in a concerted fashion through a cyclic transition state—are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-L-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme ‘toolboxes’. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

  2. Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

    Science.gov (United States)

    Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S.; Qian, Pei-Yuan

    2015-03-01

    Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning ``plug-and-play'' approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

  3. Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

    KAUST Repository

    Li, Yongxin

    2015-03-24

    Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning plug-and-playa approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

  4. The logic, experimental steps, and potential of heterologous natural product biosynthesis featuring the complex antibiotic erythromycin A produced through E. coli.

    Science.gov (United States)

    Jiang, Ming; Zhang, Haoran; Pfeifer, Blaine A

    2013-01-13

    The heterologous production of complex natural products is an approach designed to address current limitations and future possibilities. It is particularly useful for those compounds which possess therapeutic value but cannot be sufficiently produced or would benefit from an improved form of production. The experimental procedures involved can be subdivided into three components: 1) genetic transfer; 2) heterologous reconstitution; and 3) product analysis. Each experimental component is under continual optimization to meet the challenges and anticipate the opportunities associated with this emerging approach. Heterologous biosynthesis begins with the identification of a genetic sequence responsible for a valuable natural product. Transferring this sequence to a heterologous host is complicated by the biosynthetic pathway complexity responsible for product formation. The antibiotic erythromycin A is a good example. Twenty genes (totaling >50 kb) are required for eventual biosynthesis. In addition, three of these genes encode megasynthases, multi-domain enzymes each ~300 kDa in size. This genetic material must be designed and transferred to E. coli for reconstituted biosynthesis. The use of PCR isolation, operon construction, multi-cystronic plasmids, and electro-transformation will be described in transferring the erythromycin A genetic cluster to E. coli. Once transferred, the E. coli cell must support eventual biosynthesis. This process is also challenging given the substantial differences between E. coli and most original hosts responsible for complex natural product formation. The cell must provide necessary substrates to support biosynthesis and coordinately express the transferred genetic cluster to produce active enzymes. In the case of erythromycin A, the E. coli cell had to be engineered to provide the two precursors (propionyl-CoA and (2S)-methylmalonyl-CoA) required for biosynthesis. In addition, gene sequence modifications, plasmid copy number

  5. Engineering Microbial Cells for the Biosynthesis of Natural Compounds of Pharmaceutical Significance

    Directory of Open Access Journals (Sweden)

    Philippe Jeandet

    2013-01-01

    Full Text Available Microbes constitute important platforms for the biosynthesis of numerous molecules of pharmaceutical interest such as antitumor, anticancer, antiviral, antihypertensive, antiparasitic, antioxidant, immunological agents, and antibiotics as well as hormones, belonging to various chemical families, for instance, terpenoids, alkaloids, polyphenols, polyketides, amines, and proteins. Engineering microbial factories offers rich opportunities for the production of natural products that are too complex for cost-effective chemical synthesis and whose extraction from their originating plants needs the use of many solvents. Recent progresses that have been made since the millennium beginning with metabolic engineering of microorganisms for the biosynthesis of natural products of pharmaceutical significance will be reviewed.

  6. Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jiajia [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Yuan, Yun [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Lu, Danfeng; Du, Baowen [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Xiong, Liang; Shi, Jiangong [State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Yang, Lijuan [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Liu, Wanli [MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Yuan, Xiaohong [School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Zhang, Guolin, E-mail: zhanggl@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China); Wang, Fei, E-mail: wangfei@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China)

    2014-08-15

    Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds—trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol (SA-48)—were found to potently inhibit estrogen biosynthesis (IC{sub 50}: 1 μM and 0.5 μM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers. - Highlights: • Two natural products inhibited estrogen biosynthesis in human ovarian granulosa cells. • They

  7. Natural product inhibitors of fatty acid biosynthesis: synthesis of the marine microbial metabolites pseudopyronines A and B and evaluation of their anti-infective activities

    DEFF Research Database (Denmark)

    Giddens, Anna C.; Nielsen, Lone; Boshoff, Helena I.

    2007-01-01

    of pathogenic microorganisms and were found to exhibit good potency (IC50≥0.46 μg/mL) and selectivity towards Leishmania donovani. Several of the compounds inhibited recombinant fatty acid biosynthesis enzymes from both Plasmodium falciparum and Mycobacterium tuberculosis, validating these targets in the search...

  8. De novo Biosynthesis of "Non-Natural" Thaxtomin Phytotoxins.

    Science.gov (United States)

    Winn, Michael; Francis, Daniel; Micklefield, Jason

    2018-03-30

    Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to "non-natural" product target compounds. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Ribosomally Synthesized and Post-translationally Modified Peptide Natural Products: New Insights Into the Role of Leader and Core Peptides During Biosynthesis

    Science.gov (United States)

    Yang, Xiao; van der Donk, Wilfred A.

    2013-01-01

    Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with a high degree of structural diversity and a wide variety of bioactivities. Understanding the biosynthetic machinery of these RiPPs will benefit the discovery and development of new molecules with potential pharmaceutical applications. In this review, we discuss the features of the biosynthetic pathways to different RiPP classes, and propose mechanisms regarding recognition of the precursor peptide by the posttranslational modification enzymes. We propose that the leader peptides function as allosteric regulators that bind the active form of the biosynthetic enzymes in a conformational selection process. We also speculate how enzymes that generate polycyclic products of defined topologies may have been selected for during evolution. PMID:23666908

  10. Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

    Science.gov (United States)

    Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

    2017-02-22

    Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

  11. Genus Cistus: a model for exploring labdane-type diterpenes' biosynthesis and a natural source of high value products with biological, aromatic and pharmacological properties

    Science.gov (United States)

    Papaefthimiou, Dimitra; Papanikolaou, Antigoni; Falara, Vasiliki; Givanoudi, Stella; Kostas, Stefanos; Kanellis, Angelos

    2014-06-01

    The family Cistaceae (Angiosperm, Malvales) consists of 8 genera and 180 species, with 5 genera native of the Mediterranean area (Cistus, Fumara, Halimium, Helianthemum and Tuberaria). Traditionally, a number of Cistus specie have been used in Mediterranean folk medicine as herbal tea infusions for healing, digestive problems and colds, as extracts for the treatment of diseases, and as fragrances. The resin, ladano, secreted by the glandular trichomes of certain Cistus species contains a number of phytochemicals with antioxidant, antibacterial, antifungal and anticancer properties. Furthermore, total leaf aqueous extracts possess anti-influenza virus activity. All these properties have been attributed to phytochemicals such as terpenoids, including diterpenes, labdane-type diterpenes and clerodanes, phenylpropanoids, including flavonoids and ellagitannins, several groups of alkaloids and other types of secondary metabolites. In the past 20 years, research on Cistus involved chemical, biological and phylogenetic analysis but recent investigations have involved genomic and molecular approaches. Our lab is exploring the biosynthetic machinery that generates terpenoids and phenylpropanoids, with a goal to harness their numerous properties that have applications in the pharmaceutical, chemical and aromatic industries. This review focuses on the systematics, botanical characteristics, geographic distribution, chemical analyses, biological function and biosynthesis of major compounds, as well as genomic analyses and biotechnological approaches of the main Cistus species found in the Mediterranean basin, namely C. albidus, C. creticus, C. crispus, C. parviflorus, C. monspeliensis, C. populifolius, C. salviifolius, C. ladanifer, C. laurifolius and C. clusii.

  12. Pseudopterosin Biosynthesis: Aromatization of the Diterpene Cyclase Product, Elisabethatriene

    Directory of Open Access Journals (Sweden)

    Amber C. Kohl

    2003-11-01

    Full Text Available Abstract: Putative precursors in pseudopterosin biosynthesis, the hydrocarbons isoelisabethatriene (10 and erogorgiaene (11, have been identified from an extract of Pseudopterogorgia elisabethae collected in the Florida Keys. Biosynthetic experiments designed to test the utilization of these compounds in pseudopterosin production revealed that erogorgiaene is transformed to pseudopterosins A-D. Together with our previous data, it is now apparent that early steps in pseudopterosin biosynthesis involve the cyclization of geranylgeranyl diphosphate to elisabethatriene followed by the dehydrogenation and aromatization to erogorgiaene.

  13. Laser-assisted biosynthesis for noble nanoparticles production

    Science.gov (United States)

    Kukhtarev, Tatiana; Edwards, Vernessa; Kukhtareva, Nickolai; Moses, Sherita

    2014-08-01

    Extracellular Biosynthesis technique (EBS) for nanoparticles production has attracted a lot of attention as an environmentally friendly and an inexpensive methodology. Our recent research was focused on the rapid approach of the green synthesis method and the reduction of the homogeneous size distribution of nanoparticles using pulse laser application. Noble nanoparticles (NNPs) were produced using various ethanol and water plant extracts. The plants were chosen based on their biomedical applications. The plants we used were Magnolia grandiflora, Geranium, Aloe `tingtinkie', Aloe barbadensis (Aloe Vera), Eucalyptus angophoroides, Sansevieria trifasciata, Impatiens scapiflora. Water and ethanol extract, were used as reducing agents to produce the nanoparticles. The reaction process was monitored using a UV-Visible spectroscopy. NNPs were characterized by Fourier Transfer Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), and the Dynamic Light Scattering technique (DLS). During the pulse laser Nd-YAG illumination (λ=1064nm, 532nm, PE= 450mJ, 200mJ, 10 min) the blue shift of the surface plasmon resonance absorption peak was observed from ~424nm to 403nm for silver NP; and from ~530nm to 520 nm for gold NPs. In addition, NNPs solution after Nd-YAG illumination was characterized by the narrowing of the surface plasmon absorption resonance band, which corresponds to monodispersed NNPS distribution. FTIR, TEM, DLS, Zeta potential results demonstrated that NNPs were surrounded by biological molecules, which naturally stabilized nanosolutions for months. Cytotoxicity investigation of biosynthesized NNPs is in progress.

  14. 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)

  15. Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids.

    Science.gov (United States)

    El-Seedi, Hesham R; El-Said, Asmaa M A; Khalifa, Shaden A M; Göransson, Ulf; Bohlin, Lars; Borg-Karlson, Anna-Karin; Verpoorte, Rob

    2012-11-07

    Hydroxycinnamic acids are the most widely distributed phenolic acids in plants. Broadly speaking, they can be defined as compounds derived from cinnamic acid. They are present at high concentrations in many food products, including fruits, vegetables, tea, cocoa, and wine. A diet rich in hydroxycinnamic acids is thought to be associated with beneficial health effects such as a reduced risk of cardiovascular disease. The impact of hydroxycinnamic acids on health depends on their intake and pharmacokinetic properties. This review discusses their chemistry, biosynthesis, natural sources, dietary intake, and pharmacokinetic properties.

  16. Natural rubber (NR) biosynthesis: perspectives from polymer chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Barkakaty, Balaka [ORNL

    2014-01-01

    Natural rubber is an important strategic raw material for manufacturing a wide variety of industrial products. There are at least 2,500 different latex-producing plant species; however, only Hevea brasiliensis (the Brazilian rubber tree) is a commercial source. The chemical structure of natural rubber is cis-1,4-polyisoprene, but the exact structure of the head and end groups remains unknown. Since synthetic cis-1,4-polyisoprenes cannot match the superior properties of natural rubber, understanding the chemistry behind the biosynthetic process is key to finding a possible replacement. T his chapter summarizes our current understandings from the perspective of a polymer scientist by comparing synthetic polyisoprenes to natural rubber. The chapter also highlights biomimetic polymerization, research towards a synthetic match of natural rubber and the role of natural rubber in health care.

  17. Nephrotoxicity of Natural Products.

    Science.gov (United States)

    Nauffal, Mary; Gabardi, Steven

    2016-01-01

    The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education. © 2016 S. Karger AG, Basel.

  18. Bacterial cellulose biosynthesis: diversity of operons, subunits, products and functions

    Science.gov (United States)

    Römling, Ute; Galperin, Michael Y.

    2015-01-01

    Summary Recent studies of bacterial cellulose biosynthesis, including structural characterization of a functional cellulose synthase complex, provided the first mechanistic insight into this fascinating process. In most studied bacteria, just two subunits, BcsA and BcsB, are necessary and sufficient for the formation of the polysaccharide chain in vitro. Other subunits – which differ among various taxa – affect the enzymatic activity and product yield in vivo by modulating expression of biosynthesis apparatus, export of the nascent β-D-glucan polymer to the cell surface, and the organization of cellulose fibers into a higher-order structure. These auxiliary subunits play key roles in determining the quantity and structure of the resulting biofilm, which is particularly important for interactions of bacteria with higher organisms that lead to rhizosphere colonization and modulate virulence of cellulose-producing bacterial pathogens inside and outside of host cells. Here we review the organization of four principal types of cellulose synthase operons found in various bacterial genomes, identify additional bcs genes that encode likely components of the cellulose biosynthesis and secretion machinery, and propose a unified nomenclature for these genes and subunits. We also discuss the role of cellulose as a key component of biofilms formed by a variety of free-living and pathogenic bacteria and, for the latter, in the choice between acute infection and persistence in the host. PMID:26077867

  19. Antiplasmodial Natural Products

    Directory of Open Access Journals (Sweden)

    Cláudio R. Nogueira

    2011-03-01

    Full Text Available Malaria is a human infectious disease that is caused by four species of Plasmodium. It is responsible for more than 1 million deaths per year. Natural products contain a great variety of chemical structures and have been screened for antiplasmodial activity as potential sources of new antimalarial drugs. This review highlights studies on natural products with antimalarial and antiplasmodial activity reported in the literature from January 2009 to November 2010. A total of 360 antiplasmodial natural products comprised of terpenes, including iridoids, sesquiterpenes, diterpenes, terpenoid benzoquinones, steroids, quassinoids, limonoids, curcubitacins, and lanostanes; flavonoids; alkaloids; peptides; phenylalkanoids; xanthones; naphthopyrones; polyketides, including halenaquinones, peroxides, polyacetylenes, and resorcylic acids; depsidones; benzophenones; macrolides; and miscellaneous compounds, including halogenated compounds and chromenes are listed in this review.

  20. Natural products as photoprotection.

    Science.gov (United States)

    Saewan, Nisakorn; Jimtaisong, Ampa

    2015-03-01

    The rise in solar ultraviolet radiation on the earth's surface has led to a depletion of stratospheric ozone over recent decades, thus accelerating the need to protect human skin against the harmful effects of UV radiation such as erythema, edema, hyperpigmentation, photoaging, and skin cancer. There are many different ways to protect skin against UV radiation's harmful effects. The most popular way to reduce the amount of UV radiation penetrating the skin is topical application of sunscreen products that contain UV absorbing or reflecting active molecules. Based on their protection mechanism, the active molecules in sunscreens are broadly divided into inorganic and organic agents. Inorganic sunscreens reflect and scatter UV and visible radiation, while organic sunscreens absorb UV radiation and then re-emit energy as heat or light. These synthetic molecules have limited concentration according to regulation concern. Several natural compounds with UV absorption property have been used to substitute for or to reduce the quantity of synthetic sunscreen agents. In addition to UV absorption property, most natural compounds were found to act as antioxidants, anti-inflammatory, and immunomodulatory agents, which provide further protection against the damaging effects of UV radiation exposure. Compounds derived from natural sources have gained considerable attention for use in sunscreen products and have bolstered the market trend toward natural cosmetics. This adds to the importance of there being a wide selection of active molecules in sunscreen formulations. This paper summarizes a number of natural products derived from propolis, plants, algae, and lichens that have shown potential photoprotection properties against UV radiation exposure-induced skin damage. © 2015 Wiley Periodicals, Inc.

  1. Flavonoid biosynthesis controls fiber color in naturally colored cotton

    Directory of Open Access Journals (Sweden)

    Hai-Feng Liu

    2018-04-01

    Full Text Available The existence of only natural brown and green cotton fibers (BCF and GCF, respectively, as well as poor fiber quality, limits the use of naturally colored cotton (Gossypium hirsutum L.. A better understanding of fiber pigment regulation is needed to surmount these obstacles. In this work, transcriptome analysis and quantitative reverse transcription PCR revealed that 13 and 9 phenylpropanoid (metabolic pathway genes were enriched during pigment synthesis, while the differential expression of phenylpropanoid (metabolic and flavonoid metabolic pathway genes occurred among BCF, GCF, and white cotton fibers (WCF. Silencing the chalcone flavanone isomerase gene in a BCF line resulted in three fiber phenotypes among offspring of the RNAi lines: BCF, almost WCF, and GCF. The lines with almost WCF suppressed chalcone flavanone isomerase, while the lines with GCF highly expressed the glucosyl transferase (3GT gene. Overexpression of the Gh3GT or Arabidopsis thaliana 3GT gene in BCF lines resulted in GCF. Additionally, the phenylpropanoid and flavonoid metabolites of BCF and GCF were significantly higher than those of WCF as assessed by a metabolomics analysis. Thus, the flavonoid biosynthetic pathway controls both brown and green pigmentation processes. Like natural colored fibers, the transgenic colored fibers were weaker and shorter than WCF. This study shows the potential of flavonoid pathway modifications to alter cotton fibers’ color and quality.

  2. Harnessing natural product assembly lines: structure, promiscuity, and engineering.

    Science.gov (United States)

    Ladner, Christopher C; Williams, Gavin J

    2016-03-01

    Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies has been developed that enables the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and non-ribosomal peptide analogues.

  3. Natural Product Biosynthetic Diversity and Comparative Genomics of the Cyanobacteria.

    Science.gov (United States)

    Dittmann, Elke; Gugger, Muriel; Sivonen, Kaarina; Fewer, David P

    2015-10-01

    Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with intricate chemical structures and potent biological activities. The bulk of these natural products are known from just a handful of genera. Recent efforts have elucidated the mechanisms underpinning the biosynthesis of a diverse array of natural products from cyanobacteria. Many of the biosynthetic mechanisms are unique to cyanobacteria or rarely described from other organisms. Advances in genome sequence technology have precipitated a deluge of genome sequences for cyanobacteria. This makes it possible to link known natural products to biosynthetic gene clusters but also accelerates the discovery of new natural products through genome mining. These studies demonstrate that cyanobacteria encode a huge variety of cryptic gene clusters for the production of natural products, and the known chemical diversity is likely to be just a fraction of the true biosynthetic capabilities of this fascinating and ancient group of organisms. Copyright © 2015. Published by Elsevier Ltd.

  4. Natural abundance deuterium nuclear magnetic resonance spectroscopy: Study of the biosynthesis of monoterpenes

    International Nuclear Information System (INIS)

    Leopold, M.F.

    1990-01-01

    Deuterium NMR spectroscopy at natural abundance (D NMR-na) is a new technique for exploring the biosynthesis of small molecules such as monoterpenes. The analysis of relative site-specific deuterium integration values is an effective means of measuring isotope effects, and examining the regio- and stereochemistry of biosynthetic reactions. The deuterium integration values of linalyl acetate and limonene isolated from the same source were consistent and showed that proton abstraction from the postulated α-terpinyl cation intermediate to form limonene is regioselective from the methyl derived from the Cs methyl of the precursor, geranyl diphosphate. This regiochemistry was observed in limonene samples from different sources and the measured primary kinetic isotope effect ranged from 0.25 to in excess of 100 (no deuterium was removed within experimental error). Various α- and β-pinene samples were isolated and D NMR-na analysis showed evidence of isotopically sensitive partitioning of the pinylcation in the formation of these products. This spectral analysis supported published radiolabeling studies but did not require synthesis of substrates or enzyme purification. The formation of 3-carene occurs without isomerization of the double bond which was previously postulated. The olefinic deuterium of the bicyclic compound was traced to the depleted deuterium at C 2 of isopentyl diphosphate by D NMR-na data and this supported unpublished radiolabeling studies. Study of irregular monoterpenes, chrysanthemyl acetate and lyratyl acetate, showed partitioning of dimethylallyl diphosphate (DMAPP) by chrysanthemyl cyclase. The α-secondary kinetic isotope effect of 1.06-1.12, obtained from relative deuterium integration values, suggested that S N 1 ionization of one molecule of DMAPP is the first step in the condensation reaction

  5. A Natural Love of Natural Products

    OpenAIRE

    Kingston, David G. I.

    2008-01-01

    Recent research on the chemistry of natural products from the author?s group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies wit...

  6. Combinatorial synthesis of natural products

    DEFF Research Database (Denmark)

    Nielsen, John

    2002-01-01

    Combinatorial syntheses allow production of compound libraries in an expeditious and organized manner immediately applicable for high-throughput screening. Natural products possess a pedigree to justify quality and appreciation in drug discovery and development. Currently, we are seeing a rapid...... increase in application of natural products in combinatorial chemistry and vice versa. The therapeutic areas of infectious disease and oncology still dominate but many new areas are emerging. Several complex natural products have now been synthesised by solid-phase methods and have created the foundation...... for preparation of combinatorial libraries. In other examples, natural products or intermediates have served as building blocks or scaffolds in the synthesis of complex natural products, bioactive analogues or designed hybrid molecules. Finally, structural motifs from the biologically active parent molecule have...

  7. Discovery of the leinamycin family of natural products by mining actinobacterial genomes.

    Science.gov (United States)

    Pan, Guohui; Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Yang, Dong; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen; Shen, Ben

    2017-12-26

    Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm -type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.

  8. Characterization of the role of para-aminobenzoic acid biosynthesis in folate production by Lactococcus lactis

    NARCIS (Netherlands)

    Wegkamp, H.B.A.; Oorschot, van A.; Vos, de W.M.; Smid, E.J.

    2007-01-01

    The pab genes for para-aminobenzoic acid (pABA) biosynthesis in Lactococcus lactis were identified and characterized. In L. lactis NZ9000, only two of the three genes needed for pABA production were initially found. No gene coding for 4-amino-4-deoxychorismate lyase (pabC) was initially annotated,

  9. Natural products used for diabetes.

    Science.gov (United States)

    Shapiro, Karen; Gong, William C

    2002-01-01

    To review the efficacy and safety of natural products commonly used for diabetes. English and Spanish-language journals retrieved through a MEDLINE search of articles published between 1960 and December 2001 using these index terms: Opuntia, karela, gymnema, tecoma, alpha lipoic acid, thioctic acid, ginseng, panaxans, and diabetes. Natural products have long been used in traditional systems of medicine for diabetes. Products in common use include nopal (prickly pear cactus), fenu-greek, karela (bitter melon), gymnema, ginseng, tronadora, chromium, and alpha-lipoic acid. The popularity of these products varies among people of different ethnicities. Nopal is the most commonly used herbal hypoglycemic among persons of Mexican descent. Karela is more commonly used by persons from Asian countries. Some of these agents have gained universal appeal. For a select number of products, studies have revealed single or multiple mechanisms of action. For several of these, high soluble fiber content is a contributing factor. Based on the available evidence, several natural products in common use can lower blood glucose in patients with diabetes. Commonly used natural products often have a long history of traditional use, and pharmacists who have a stronger understanding of these products are better positioned to counsel patients on their appropriate use.

  10. Novel Artificial Natural Products Against Breast Cancer Through Combinatorial Biosynthesis

    Science.gov (United States)

    2002-07-01

    P.O. Box 250140, Charleston, South Carolina 29425, Departamento de Biologfa Funcional e Instituto Universitario de Oncologfa del Principado de Asturias...Biologia Funcional e Instituto Universitario de Oncologia del Principado de Asturias (I. U.O.P.A.), Universidad de Oviedo, 33006 Oviedo, Spain, and...which allow modifications to be made in regions of the molecule gastrointestinal, hepatic, renal , and bone marrow toxicity identified as crucial for

  11. Synthesis of Polycyclic Natural Products

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Tuan Hoang [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    With the continuous advancements in molecular biology and modern medicine, organic synthesis has become vital to the support and extension of those discoveries. The isolations of new natural products allow for the understanding of their biological activities and therapeutic value. Organic synthesis is employed to aid in the determination of the relationship between structure and function of these natural products. The development of synthetic methodologies in the course of total syntheses is imperative for the expansion of this highly interdisciplinary field of science. In addition to the practical applications of total syntheses, the structural complexity of natural products represents a worthwhile challenge in itself. The pursuit of concise and efficient syntheses of complex molecules is both gratifying and enjoyable.

  12. Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product.

    Science.gov (United States)

    Dailey, Harry A; Dailey, Tamara A; Gerdes, Svetlana; Jahn, Dieter; Jahn, Martina; O'Brian, Mark R; Warren, Martin J

    2017-03-01

    The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzyme-step process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gram-negative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized. Copyright © 2017 American Society for Microbiology.

  13. Natural Products from Mangrove Actinomycetes

    Directory of Open Access Journals (Sweden)

    Dong-Bo Xu

    2014-05-01

    Full Text Available Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery.

  14. Natural Products from Mangrove Actinomycetes

    Science.gov (United States)

    Xu, Dong-Bo; Ye, Wan-Wan; Han, Ying; Deng, Zi-Xin; Hong, Kui

    2014-01-01

    Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery. PMID:24798926

  15. Aminobenzoates as building blocks for natural product assembly lines.

    Science.gov (United States)

    Walsh, Christopher T; Haynes, Stuart W; Ames, Brian D

    2012-01-01

    The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate pathway metabolite chorismate while the meta-isomer is not available by that route and starts from UDP-3-aminoglucose. PABA is largely funnelled into folate biosynthesis while anthranilate is the scaffold for biosynthetic elaboration into many natural heterocycles, most notably with its role in indole formation for tryptophan biosynthesis. Anthranilate is also converted to benzodiazepinones, fumiquinazolines, quinoxalines, phenoxazines, benzoxazolinates, quinolones, and phenazines, often with redox enzyme participation. The 5-hydroxy form of 3-aminobenzaote is the starter unit for ansa-bridged rifamycins, ansamitocins, and geldanamycins, whereas regioisomers 2-hydroxy, 4-hydroxy and 2,4-dihydroxy-3-aminobenzoate are key components of antimycin, grixazone, and platencin and platensimycin biosynthesis, respectively. The enzymatic mechanisms for generation of the aminobenzoate regioisomers and their subsequent utilization for diverse heterocycle and macrocycle construction are examined.

  16. Engineering plastid fatty acid biosynthesis to improve food quality and biofuel production in higher plants.

    Science.gov (United States)

    Rogalski, Marcelo; Carrer, Helaine

    2011-06-01

    The ability to manipulate plant fatty acid biosynthesis by using new biotechnological approaches has allowed the production of transgenic plants with unusual fatty acid profile and increased oil content. This review focuses on the production of very long chain polyunsaturated fatty acids (VLCPUFAs) and the increase in oil content in plants using molecular biology tools. Evidences suggest that regular consumption of food rich in VLCPUFAs has multiple positive health benefits. Alternative sources of these nutritional fatty acids are found in cold-water fishes. However, fish stocks are in severe decline because of decades of overfishing, and also fish oils can be contaminated by the accumulation of toxic compounds. Recently, there is also an increase in oilseed use for the production of biofuels. This tendency is partly associated with the rapidly rising costs of petroleum, increased concern about the environmental impact of fossil oil and the attractive need to develop renewable sources of fuel. In contrast to this scenario, oil derived from crop plants is normally contaminant free and less environmentally aggressive. Genetic engineering of the plastid genome (plastome) offers a number of attractive advantages, including high-level foreign protein expression, marker-gene excision and transgene containment because of maternal inheritance of plastid genome in most crops. Here, we describe the possibility to improve fatty acid biosynthesis in plastids, production of new fatty acids and increase their content in plants by genetic engineering of plastid fatty acid biosynthesis via plastid transformation. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  17. Silencing the lettuce homologs of small rubber particle protein does not influence natural rubber biosynthesis in lettuce (Lactuca sativa).

    Science.gov (United States)

    Chakrabarty, Romit; Qu, Yang; Ro, Dae-Kyun

    2015-05-01

    Natural rubber, cis-1,4-polyisoprene, is an important raw material in chemical industries, but its biosynthetic mechanism remains elusive. Natural rubber is known to be synthesized in rubber particles suspended in laticifer cells in the Brazilian rubber tree (Hevea brasiliensis). In the rubber tree, rubber elongation factor (REF) and its homolog, small rubber particle protein (SRPP), were found to be the most abundant proteins in rubber particles, and they have been implicated in natural rubber biosynthesis. As lettuce (Lactuca sativa) can synthesize natural rubber, we utilized this annual, transformable plant to examine in planta roles of the lettuce REF/SRPP homologs by RNA interference. Among eight lettuce REF/SRPP homologs identified, transcripts of two genes (LsSRPP4 and LsSRPP8) accounted for more than 90% of total transcripts of REF/SRPP homologs in lettuce latex. LsSRPP4 displays a typical primary protein sequence as other REF/SRPP, while LsSRPP8 is twice as long as LsSRPP4. These two major LsSRPP transcripts were individually and simultaneously silenced by RNA interference, and relative abundance, polymer molecular weight, and polydispersity of natural rubber were analyzed from the LsSRPP4- and LsSRPP8-silenced transgenic lettuce. Despite previous data suggesting the implications of REF/SRPP in natural rubber biosynthesis, qualitative and quantitative alterations of natural rubber could not be observed in transgenic lettuce lines. It is concluded that lettuce REF/SRPP homologs are not critically important proteins in natural rubber biosynthesis in lettuce. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Combinatorial biosynthesis of medicinal plant secondary metabolites

    NARCIS (Netherlands)

    Julsing, Mattijs K.; Koulman, Albert; Woerdenbag, Herman J.; Quax, Wim J.; Kayser, Oliver

    2006-01-01

    Combinatorial biosynthesis is a new tool in the generation of novel natural products and for the production of rare and expensive natural products. The basic concept is combining metabolic pathways in different organisms on a genetic level. As a consequence heterologous organisms provide precursors

  19. In silico Design of "Un-Natural" Natural Products

    Directory of Open Access Journals (Sweden)

    Zucko; J. ...(et al.

    2008-05-01

    Full Text Available Polyketides and non-ribosomal peptides represent a large class of structurally diverse natural products much studied over recent years because the enzymes that synthesise them, the modular polyketide synthases (PKSs and the non-ribosomal peptide synthetases (NRPSs, share striking architectural similarities that can be exploited to generate "un-natural" natural products. PKS and NRPS proteins are multifunctional, composed of a co-linear arrangement of discrete protein domains representing each enzymic activity needed for chain elongation using either carboxylic acid or amino acid building blocks. Each domain is housed within larger modules which form the complex. Polyketide and peptide antibiotics, antifungals, antivirals, cytostatics, immunosuppressants, antihypertensives, antidiabetics, antimalarials and anticholesterolemics are in clinical use. Of commercial importance are also polyketide and peptide antiparasitics, coccidiostatics,animal growth promoters and natural insecticides.Polyketides are assembled through serial condensations of activated coenzyme-A thioester monomers derived from simple organic acids such as acetate, propionate and butyrate. The choice of organic acid allows the introduction of different chiral centres into the polyketide backbone. The active sites required for condensation include an acyltransferase (AT, an acyl carrier protein (ACP and a ß-ketoacylsynthase (KS. Each condensation results in a ß-keto group that undergoes all, some or none of a series of processing steps. Active sites that perform these reactions are contained within the following domains; ketoreductase (KR, dehydratase (DH and an enoylreductase (ER. The absence of any ß-keto processing results in the incorporation of a ketone group into the growing polyketide chain, a KR alone gives rise to a hydroxyl moiety, a KR and DH produce an alkene, while the combination of KR, DH and ER domains lead to complete reduction to an alkane. Most often, the last

  20. A Lettuce (Lactuca sativa) Homolog of Human Nogo-B Receptor Interacts with cis-Prenyltransferase and Is Necessary for Natural Rubber Biosynthesis*

    Science.gov (United States)

    Qu, Yang; Chakrabarty, Romit; Tran, Hue T.; Kwon, Eun-Joo G.; Kwon, Moonhyuk; Nguyen, Trinh-Don; Ro, Dae-Kyun

    2015-01-01

    Natural rubber (cis-1,4-polyisoprene) is an indispensable biopolymer used to manufacture diverse consumer products. Although a major source of natural rubber is the rubber tree (Hevea brasiliensis), lettuce (Lactuca sativa) is also known to synthesize natural rubber. Here, we report that an unusual cis-prenyltransferase-like 2 (CPTL2) that lacks the conserved motifs of conventional cis-prenyltransferase is required for natural rubber biosynthesis in lettuce. CPTL2, identified from the lettuce rubber particle proteome, displays homology to a human NogoB receptor and is predominantly expressed in latex. Multiple transgenic lettuces expressing CPTL2-RNAi constructs showed that a decrease of CPTL2 transcripts (3–15% CPTL2 expression relative to controls) coincided with the reduction of natural rubber as low as 5%. We also identified a conventional cis-prenyltransferase 3 (CPT3), exclusively expressed in latex. In subcellular localization studies using fluorescent proteins, cytosolic CPT3 was relocalized to endoplasmic reticulum by co-occurrence of CPTL2 in tobacco and yeast at the log phase. Furthermore, yeast two-hybrid data showed that CPTL2 and CPT3 interact. Yeast microsomes containing CPTL2/CPT3 showed enhanced synthesis of short cis-polyisoprenes, but natural rubber could not be synthesized in vitro. Intriguingly, a homologous pair CPTL1/CPT1, which displays ubiquitous expressions in lettuce, showed a potent dolichol biosynthetic activity in vitro. Taken together, our data suggest that CPTL2 is a scaffolding protein that tethers CPT3 on endoplasmic reticulum and is necessary for natural rubber biosynthesis in planta, but yeast-expressed CPTL2 and CPT3 alone could not synthesize high molecular weight natural rubber in vitro. PMID:25477521

  1. A lettuce (Lactuca sativa) homolog of human Nogo-B receptor interacts with cis-prenyltransferase and is necessary for natural rubber biosynthesis.

    Science.gov (United States)

    Qu, Yang; Chakrabarty, Romit; Tran, Hue T; Kwon, Eun-Joo G; Kwon, Moonhyuk; Nguyen, Trinh-Don; Ro, Dae-Kyun

    2015-01-23

    Natural rubber (cis-1,4-polyisoprene) is an indispensable biopolymer used to manufacture diverse consumer products. Although a major source of natural rubber is the rubber tree (Hevea brasiliensis), lettuce (Lactuca sativa) is also known to synthesize natural rubber. Here, we report that an unusual cis-prenyltransferase-like 2 (CPTL2) that lacks the conserved motifs of conventional cis-prenyltransferase is required for natural rubber biosynthesis in lettuce. CPTL2, identified from the lettuce rubber particle proteome, displays homology to a human NogoB receptor and is predominantly expressed in latex. Multiple transgenic lettuces expressing CPTL2-RNAi constructs showed that a decrease of CPTL2 transcripts (3-15% CPTL2 expression relative to controls) coincided with the reduction of natural rubber as low as 5%. We also identified a conventional cis-prenyltransferase 3 (CPT3), exclusively expressed in latex. In subcellular localization studies using fluorescent proteins, cytosolic CPT3 was relocalized to endoplasmic reticulum by co-occurrence of CPTL2 in tobacco and yeast at the log phase. Furthermore, yeast two-hybrid data showed that CPTL2 and CPT3 interact. Yeast microsomes containing CPTL2/CPT3 showed enhanced synthesis of short cis-polyisoprenes, but natural rubber could not be synthesized in vitro. Intriguingly, a homologous pair CPTL1/CPT1, which displays ubiquitous expressions in lettuce, showed a potent dolichol biosynthetic activity in vitro. Taken together, our data suggest that CPTL2 is a scaffolding protein that tethers CPT3 on endoplasmic reticulum and is necessary for natural rubber biosynthesis in planta, but yeast-expressed CPTL2 and CPT3 alone could not synthesize high molecular weight natural rubber in vitro. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Molecular cloning and characterization of (+)-epi-α-bisabolol synthase, catalyzing the first step in the biosynthesis of the natural sweetener, hernandulcin, in Lippia dulcis.

    Science.gov (United States)

    Attia, Mohamed; Kim, Soo-Un; Ro, Dae-Kyun

    2012-11-01

    Hernandulcin, a C15 sesquiterpene ketone, is a natural sweetener isolated from the leaves of Lippia dulcis. It is a promising sugar substitute due to its safety and low caloric potential. However, the biosynthesis of hernandulcin in L. dulcis remains unknown. The first biochemical step of hernandulcin is the synthesis of (+)-epi-α-bisabolol from farnesyl diphosphate, which is presumed to be catalyzed by a unique sesquiterpene synthase in L. dulcis. In order to decipher hernandulcin biosynthesis, deep transcript sequencings (454 and Illumina) were performed, which facilitated the molecular cloning of five new sesquiterpene synthase cDNAs from L. dulcis. In vivo activity evaluation of these cDNAs in yeast identified them as the sesquiterpene synthases for α-copaene/δ-cadinene, bicyclogermacrene, β-caryophyllene, trans-α-bergamotene, and α-bisabolol. The engineered yeast could synthesize a significant amount (~0.3 mg per mL) of α-bisabolol in shake-flask cultivation. This efficient in vivo production was congruent with the competent kinetic properties of recombinant α-bisabolol synthase (K(m) 4.8 μM and k(cat) 0.04 s(-1)). Detailed chemical analyses of the biosynthesized α-bisabolol confirmed its configuration to be (+)-epi-α-bisabolol, the core skeleton of hernandulcin. These results demonstrated that enzymatic, stereoselective synthesis of (+)-epi-α-bisabolol can be achieved, promising the heterologous production of a natural sweetener, hernandulcin. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Leveraging ecological theory to guide natural product discovery.

    Science.gov (United States)

    Smanski, Michael J; Schlatter, Daniel C; Kinkel, Linda L

    2016-03-01

    Technological improvements have accelerated natural product (NP) discovery and engineering to the point that systematic genome mining for new molecules is on the horizon. NP biosynthetic potential is not equally distributed across organisms, environments, or microbial life histories, but instead is enriched in a number of prolific clades. Also, NPs are not equally abundant in nature; some are quite common and others markedly rare. Armed with this knowledge, random 'fishing expeditions' for new NPs are increasingly harder to justify. Understanding the ecological and evolutionary pressures that drive the non-uniform distribution of NP biosynthesis provides a rational framework for the targeted isolation of strains enriched in new NP potential. Additionally, ecological theory leads to testable hypotheses regarding the roles of NPs in shaping ecosystems. Here we review several recent strain prioritization practices and discuss the ecological and evolutionary underpinnings for each. Finally, we offer perspectives on leveraging microbial ecology and evolutionary biology for future NP discovery.

  4. Natural Products and HIV/AIDS.

    Science.gov (United States)

    Cary, Daniele C; Peterlin, B Matija

    2018-01-01

    The study of natural products in biomedical research is not a modern concept. Many of the most successful medical therapeutics are derived from natural products, including those studied in the field of HIV/AIDS. Biomedical research has a rich history of discovery based on screens of medicinal herbs and traditional medicine practices. Compounds derived from natural products, which repress HIV and those that activate latent HIV, have been reported. It is important to remember the tradition in medical research to derive therapies based on these natural products and to overcome the negative perception of natural products as an "alternative medicine."

  5. Biocombinatorial Engineering of Fungal PKS-NRPS Hybrids for Production of Novel Synthetic Natural Products

    DEFF Research Database (Denmark)

    Nielsen, Maria Lund

    encoding a PKS-NRPS hybrid responsible for the production of a medically relevant compound in Talaromyces atroroseus. To the best of my knowledge, this study represents the first example of reverse engineering of a Talaromyces species. In the fourth study (chapter 5), I used the CRISPR-Cas9 system...... structure optimization. Within the last decade, an alternative approach for expanding natural product chemodiversity has been applied. This strategy, known as combinatorial biosynthesis, involves the re-engineering of biosynthetic pathways and ultimately the rational engineering of new natural product...... analogs. This field, however, has proved very challenging and many engineering efforts have resulted in enzymatic loss-of-function or reduced yields. Thus, the future success in combinatorial biosynthetic studies requires a thorough understanding of the structure and function of biosynthetic enzymes...

  6. Methionine sulfoximine supplementation enhances productivity in GS-CHOK1SV cell lines through glutathione biosynthesis.

    Science.gov (United States)

    Feary, Marc; Racher, Andrew J; Young, Robert J; Smales, C Mark

    2017-01-01

    In Lonza Biologics' GS Gene Expression System™, recombinant protein-producing GS-CHOK1SV cell lines are generated by transfection with an expression vector encoding both GS and the protein product genes followed by selection in MSX and glutamine-free medium. MSX is required to inhibit endogenous CHOK1SV GS, and in effect create a glutamine auxotrophy in the host that can be complemented by the expression vector encoded GS in selected cell lines. However, MSX is not a specific inhibitor of GS as it also inhibits the activity of GCL (a key enzyme in the glutathione biosynthesis pathway) to a similar extent. Glutathione species (GSH and GSSG) have been shown to provide both oxidizing and reducing equivalents to ER-resident oxidoreductases, raising the possibility that selection for transfectants with increased GCL expression could result in the isolation of GS-CHOKISV cell lines with improved capacity for recombinant protein production. In this study we have begun to address the relationship between MSX supplementation, the amount of intracellular GCL subunit and mAb production from a panel of GS-CHOK1SV cell lines. We then evaluated the influence of reduced GCL activity on batch culture of an industrially relevant mAb-producing GS-CHOK1SV cell line. To the best of our knowledge, this paper describes for the first time the change in expression of GCL subunits and recombinant mAb production in these cell lines with the degree of MSX supplementation in routine subculture. Our data also shows that partial inhibition of GCL activity in medium containing 75 µM MSX increases mAb productivity, and its more specific inhibitor BSO used at a concentration of 80 µM in medium increases the specific rate of mAb production eight-fold and the concentration in harvest medium by two-fold. These findings support a link between the inhibition of glutathione biosynthesis and recombinant protein production in industrially relevant systems and provide a process-driven method for

  7. Teaching 'natural product chemistry' in Tanzania | Buchanan ...

    African Journals Online (AJOL)

    Natural products 'historically' and 'today' have vast importance. This article describes the course 'Natural Product Chemistry', a new course in the 2011/2012 academic year in the Faculty of Natural and Applied Sciences at St. John's University of Tanzania. It reveals how the course has been applied to the African and ...

  8. Learning Organic Chemistry Through Natural Products

    Indian Academy of Sciences (India)

    Higher Learning. ... The Series on "learning Organic Chemistry Through Natural Products". Nature is a remarkable ... skeletal structure to the interior electronic configu- ration ... Among the advantages of this approach are the fact that unlike the.

  9. Green biosynthesis of silver nanoparticles using pomegranate peel and inhibitory effects of the nanoparticles on aflatoxin production

    International Nuclear Information System (INIS)

    Monira, A.O.; Mohammad, M.A.; Ashraf, H.A.

    2017-01-01

    In this work, pomegranate peel has been used as a natural and safe method for biosynthesis of silver nanoparticles. The synthesis of silver nanoparticles was confirmed using UV spectroscopy, which showed a peak around a wavelength of 437 nm. The morphology showed spherical and monodispersed nanoparticles with a size range between 5-50 nm. Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), X-ray diffraction (XRD) experiments revealed their crystalline nature. Active functional groups in the synthesized silver nanoparticles were determined using Fourier transform infrared (FTIR) spectrometers contained four bands at 3281.21 cm/sup -1/, possibly indicating the participationof O-H functional group. The peak take place at 1,636.22 cm/sup -1/ may be pointed to C = N bending in the amide group or C = O stretching in carboxyl. Transfer in this peak (from 1,641 to 1,643 cm/sup -1/) shown the possible role of amino groups or carboxyl in nanoparticle synthesis. The peaks at 431.95 and 421.28 cm/sup -1/ be related to AgNPs bonding with oxygen from hydroxyl groups which confirm the role of pomegranate peel as a reducing agent. Furthermore, we investigated effects of these nanoparticles on aflatoxin B1 production by the fungus Aspergillus flavus, isolated from hazelnut. The results found that aflatoxin production in all A. flavus isolates decreased with an increase in the concentration of silver nanoparticles. Maximum suppression of aflatoxin production was recorded at a nanoparticle concentration of 150 ppm. (author)

  10. Fatty acid biosynthesis is involved in the production of hepatitis B virus particles

    International Nuclear Information System (INIS)

    Okamura, Hitomi; Nio, Yasunori; Akahori, Yuichi; Kim, Sulyi; Watashi, Koichi; Wakita, Takaji; Hijikata, Makoto

    2016-01-01

    Hepatitis B virus (HBV) proliferates in hepatocytes after infection, but the host factors that contribute to the HBV lifecycle are poorly understood at the molecular level. We investigated whether fatty acid biosynthesis (FABS), which was recently reported to contribute to the genomic replication of hepatitis C virus, plays a role in HBV proliferation. We examined the effects of inhibitors of the enzymes in the FABS pathway on the HBV lifecycle by using recombinant HBV-producing cultured cells and found that the extracellular HBV DNA level, reflecting HBV particle production, was decreased by treatment with inhibitors suppressed the synthesis of long-chain saturated fatty acids with little cytotoxicity. The reduced HBV DNA level was reversed when palmitic acid, which is the product of fatty acid synthase (FAS) during FABS, was used simultaneously with the inhibitor. We also observed that the amount of intracellular HBV DNA in the cells was increased by FAS inhibitor treatment, suggesting that FABS is associated with HBV particle production but not its genome replication. This suggests that FABS might be a potent target for anti-HBV drug with a mode of action different from current HBV therapy. -- Highlights: •Inhibitors of ACC1 and FAS but not SCD1 decreased production of extracellular HBV DNA. •Products of FABS, long chain fatty acids, increased production of extracellular HBV DNA. •FAS inhibitor increased intracellular levels of HBV DNA and HBcAg. •FABS was suggested to contribute to HBV particle production without significant relation with secretory pathway of the cells.

  11. Fatty acid biosynthesis is involved in the production of hepatitis B virus particles

    Energy Technology Data Exchange (ETDEWEB)

    Okamura, Hitomi [Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyoku, Kyoto 606-8501 (Japan); Nio, Yasunori, E-mail: yasunori.nio@takeda.com [Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555 (Japan); Akahori, Yuichi [Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyoku, Kyoto 606-8501 (Japan); Kim, Sulyi [Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Watashi, Koichi [Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640 (Japan); Department of Applied Biological Science, Tokyo University of Sciences, Noda 278-8510 (Japan); CREST, Japan Science and Technology Agency (JST), Saitama 332-0012 (Japan); Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640 (Japan); Hijikata, Makoto, E-mail: mhijikat@virus.kyoto-u.ac.jp [Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyoku, Kyoto 606-8501 (Japan)

    2016-06-17

    Hepatitis B virus (HBV) proliferates in hepatocytes after infection, but the host factors that contribute to the HBV lifecycle are poorly understood at the molecular level. We investigated whether fatty acid biosynthesis (FABS), which was recently reported to contribute to the genomic replication of hepatitis C virus, plays a role in HBV proliferation. We examined the effects of inhibitors of the enzymes in the FABS pathway on the HBV lifecycle by using recombinant HBV-producing cultured cells and found that the extracellular HBV DNA level, reflecting HBV particle production, was decreased by treatment with inhibitors suppressed the synthesis of long-chain saturated fatty acids with little cytotoxicity. The reduced HBV DNA level was reversed when palmitic acid, which is the product of fatty acid synthase (FAS) during FABS, was used simultaneously with the inhibitor. We also observed that the amount of intracellular HBV DNA in the cells was increased by FAS inhibitor treatment, suggesting that FABS is associated with HBV particle production but not its genome replication. This suggests that FABS might be a potent target for anti-HBV drug with a mode of action different from current HBV therapy. -- Highlights: •Inhibitors of ACC1 and FAS but not SCD1 decreased production of extracellular HBV DNA. •Products of FABS, long chain fatty acids, increased production of extracellular HBV DNA. •FAS inhibitor increased intracellular levels of HBV DNA and HBcAg. •FABS was suggested to contribute to HBV particle production without significant relation with secretory pathway of the cells.

  12. Super Natural II--a database of natural products.

    Science.gov (United States)

    Banerjee, Priyanka; Erehman, Jevgeni; Gohlke, Björn-Oliver; Wilhelm, Thomas; Preissner, Robert; Dunkel, Mathias

    2015-01-01

    Natural products play a significant role in drug discovery and development. Many topological pharmacophore patterns are common between natural products and commercial drugs. A better understanding of the specific physicochemical and structural features of natural products is important for corresponding drug development. Several encyclopedias of natural compounds have been composed, but the information remains scattered or not freely available. The first version of the Supernatural database containing ∼ 50,000 compounds was published in 2006 to face these challenges. Here we present a new, updated and expanded version of natural product database, Super Natural II (http://bioinformatics.charite.de/supernatural), comprising ∼ 326,000 molecules. It provides all corresponding 2D structures, the most important structural and physicochemical properties, the predicted toxicity class for ∼ 170,000 compounds and the vendor information for the vast majority of compounds. The new version allows a template-based search for similar compounds as well as a search for compound names, vendors, specific physical properties or any substructures. Super Natural II also provides information about the pathways associated with synthesis and degradation of the natural products, as well as their mechanism of action with respect to structurally similar drugs and their target proteins. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. An Overview of Some Natural Products with Two A-Level Science Club Natural Products Experiments

    Science.gov (United States)

    Sosabowski, Michael Hal; Olivier, George W. J.; Jawad, Hala; Maatta, Sieja

    2017-01-01

    Natural products are ubiquitous in nature but do not form a large proportion of the A-level syllabuses in the UK. In this article we briefly discuss a small selection of natural products, focusing on alcohols, aldehydes and ketones, and alkaloids. We then outline two natural product experiments that are suitable for A-level chemistry clubs or…

  14. Food production and nature conservation

    NARCIS (Netherlands)

    Gordon, Iain J.; Squire, Geoff R.; Prins, Herbert H.T.

    2016-01-01

    Feeding the world's growing human population is increasingly challenging, especially as more people adopt a western diet and lifestyle. Doing so without causing damage to nature poses an even greater challenge. This book argues that in order to create a sustainable food supply whilst conserving

  15. Natural Connections on Riemannian Product Manifolds

    OpenAIRE

    Gribacheva, Dobrinka

    2011-01-01

    A Riemannian almost product manifold with integrable almost product structure is called a Riemannian product manifold. In the present paper the natural connections on such manifolds are studied, i.e. the linear connections preserving the almost product structure and the Riemannian metric.

  16. A root specific induction of carotenoid biosynthesis contributes to ABA production upon salt stress in arabidopsis.

    Directory of Open Access Journals (Sweden)

    M Águila Ruiz-Sola

    Full Text Available Abscisic acid (ABA is a hormone that plays a vital role in mediating abiotic stress responses in plants. Salt exposure induces the synthesis of ABA through the cleavage of carotenoid precursors (xanthophylls, which are found at very low levels in roots. Here we show that de novo ABA biosynthesis in salt-treated Arabidopsis thaliana roots involves an organ-specific induction of the carotenoid biosynthetic pathway. Upregulation of the genes encoding phytoene synthase (PSY and other enzymes of the pathway producing ABA precursors was observed in roots but not in shoots after salt exposure. A pharmacological block of the carotenoid pathway substantially reduced ABA levels in stressed roots, confirming that an increase in carotenoid accumulation contributes to fuel hormone production after salt exposure. Treatment with exogenous ABA was also found to upregulate PSY expression only in roots, suggesting an organ-specific feedback regulation of the carotenoid pathway by ABA. Taken together, our results show that the presence of high concentrations of salt in the growth medium rapidly triggers a root-specific activation of the carotenoid pathway, probably to ensure a proper supply of ABA precursors required for a sustained production of the hormone.

  17. Suppression of phospholipid biosynthesis by cerulenin in the condensed Single-Protein-Production (cSPP) system

    International Nuclear Information System (INIS)

    Mao, Lili; Inoue, Koichi; Tao, Yisong; Montelione, Gaetano T.; McDermott, Ann E.; Inouye, Masayori

    2011-01-01

    Using the single-protein-production (SPP) system, a protein of interest can be exclusively produced in high yield from its ACA-less gene in Escherichia coli expressing MazF, an ACA-specific mRNA interferase. It is thus feasible to study a membrane protein by solid-state NMR (SSNMR) directly in natural membrane fractions. In developing isotope-enrichment methods, we observed that 13 C was also incorporated into phospholipids, generating spurious signals in SSNMR spectra. Notable, with the SPP system a protein can be produced in total absence of cell growth caused by antibiotics. Here, we demonstrate that cerulenin, an inhibitor of phospholipid biosynthesis, can suppress isotope incorporation in the lipids without affecting membrane protein yield in the SPP system. SSNMR analysis of ATP synthase subunit c, an E. coli inner membrane protein, produced by the SPP method using cerulenin revealed that 13 C resonance signals from phospholipid were markedly reduced, while signals for the isotope-enriched protein were clearly present.

  18. Learning Organic Chemistry Through Natural Products

    Indian Academy of Sciences (India)

    SERIES I ARTICLE. Learning Organic Chemistry. Through Natural Products. 2. Determination of Absolute Stereochemistry. N R Krishnaswamy was initiated into the world of natural products by T R. Seshadri at University of. Delhi and has carried on the glorious traditions of his mentor. He has taught at Bangalore University,.

  19. Nigerian Journal of Natural Products and Medicine

    African Journals Online (AJOL)

    Nigerian Journal of Natural Products and Medicine is published by the Nigerian Society of Pharmacognosy, a non profit organisation established in 1982 dedicated to the promotion of Pharmacognosy, Natural Products and Traditional Medicine. It has a current circulation of about 500 to scientists in Nigeria and abroad.

  20. Procurement of exogenous ammonia by the swallowtail butterfly, Papilio polytes, for protein biosynthesis and sperm production

    Science.gov (United States)

    Honda, Keiichi; Takase, Hiroyuki; Ômura, Hisashi; Honda, Hiroshi

    2012-09-01

    How to acquire sufficient quantity of nitrogen is a pivotal issue for herbivores, particularly for lepidopterans (butterflies and moths) of which diet quality greatly differs among their life stages. Male Lepidoptera often feed from mud puddles, dung, and carrion, a behavior known as puddling, which is thought to be supplementary feeding targeted chiefly at sodium. During copulation, males transfer a spermatophore to females that contains, besides sperm, nutrients (nuptial gifts) rich in sodium, proteins, and amino acids. However, it is still poorly understood how adults, mostly nectarivores, extract nitrogen from the environment. We examined the availability of two ubiquitous inorganic nitrogenous ions in nature, viz. ammonium (or ammonia) and nitrate ions, as nutrients in a butterfly, and show that exogenous ammonia ingested by adult males of the swallowtail, Papilio polytes, can serve as a resource for protein biosynthesis. Feeding experiments with 15N-labeled ammonium chloride revealed that nitrogen was incorporated into eupyrene spermatozoa, seminal protein, and thoracic muscle. Ammonia uptake by males significantly increased the number of eupyrene sperms in the reproductive tract tissues. The females also had the capacity to assimilate ammonia into egg protein. Consequently, it is evident that acquired ammonia is utilized for the replenishment of proteins allocable for reproduction and somatic maintenance. The active exploitation of exogenous ammonia as a nutrient by a butterfly would foster better understanding of the foraging and reproductive strategies in insects.

  1. Triterpene biosynthesis in plants.

    Science.gov (United States)

    Thimmappa, Ramesha; Geisler, Katrin; Louveau, Thomas; O'Maille, Paul; Osbourn, Anne

    2014-01-01

    The triterpenes are one of the most numerous and diverse groups of plant natural products. They are complex molecules that are, for the most part, beyond the reach of chemical synthesis. Simple triterpenes are components of surface waxes and specialized membranes and may potentially act as signaling molecules, whereas complex glycosylated triterpenes (saponins) provide protection against pathogens and pests. Simple and conjugated triterpenes have a wide range of applications in the food, health, and industrial biotechnology sectors. Here, we review recent developments in the field of triterpene biosynthesis, give an overview of the genes and enzymes that have been identified to date, and discuss strategies for discovering new triterpene biosynthetic pathways.

  2. Bioactive natural products from novel microbial sources.

    Science.gov (United States)

    Challinor, Victoria L; Bode, Helge B

    2015-09-01

    Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics. © 2015 New York Academy of Sciences.

  3. Biosynthesis and metabolic engineering of palmitoleate production, an important contributor to human health and sustainable industry.

    Science.gov (United States)

    Wu, Yongmei; Li, Runzhi; Hildebrand, David F

    2012-10-01

    Palmitoleate (cis-Δ9-16:1) shows numerous health benefits such as increased cell membrane fluidity, reduced inflammation, protection of the cardiovascular system, and inhibition of oncogenesis. Plant oils containing this unusual fatty acid can also be sustainable feedstocks for producing industrially important and high-demand 1-octene. Vegetable oils rich in palmitoleate are the ideal candidates for biodiesel production. Several wild plants are known that can synthesize high levels of palmitoleate in seeds. However, low yields and poor agronomic characteristics of these plants limit their commercialization. Metabolic engineering has been developed to create oilseed crops that accumulate high levels of palmitoleate or other unusual fatty acids, and significant advances have been made recently in this field, particularly using the model plant Arabidopsis as the host. The engineered targets for enhancing palmitoleate synthesis include overexpression of Δ9 desaturase from mammals, yeast, fungi, and plants, down-regulating KASII, coexpression of an ACP-Δ9 desaturase in plastids and CoA-Δ9 desaturase in endoplasmic reticulum (ER), and optimizing the metabolic flux into triacylglycerols (TAGs). This review will mainly describe the recent progress towards producing palmitoleate in transgenic plants by metabolic engineering along with our current understanding of palmitoleate biosynthesis and its regulation, as well as highlighting the bottlenecks that require additional investigation by combining lipidomics, transgenics and other "-omics" tools. A brief review of reported health benefits and non-food uses of palmitoleate will also be covered. Copyright © 2012. Published by Elsevier Ltd.

  4. Plant storage proteins – the main nourisching products – from biosynthesis to cellular storage depots

    Directory of Open Access Journals (Sweden)

    Agnieszka Chmielnicka

    2017-06-01

    Full Text Available Storage proteins of legumes are one of the main components of the human and animal diet. The substances collected in their seeds have the pro-health values, supporting the prevention of many civilization diseases. However, there are still many uncertainties about the mechanisms leading to the production of nutritious seeds. It is also difficult to identify which of their constituents and in what final form are responsible for the observed protective effects in vivo. In this work, on the background of different types of storage proteins, these deposited mainly in legumes were in the focus of interest. They were characterized on the example of pea (Pisum sativum proteins. Mechanisms associated with their biosynthesis and transport to specific cellular compartments was presented. Ways of their post-translational processing, segregation and storage in the specific vacuoles were also discussed. Therefore, the paper presents the state-of-the-art knowledge concerning the processes making the accumulated protein deposits ready to use by plants, animals and humans.

  5. Natural gas production verification tests

    International Nuclear Information System (INIS)

    1992-02-01

    This Environmental Assessment (EA) has been prepared by the Department of Energy (DOE) in compliance with the requirements of the National Environmental Policy Act of 1969. The Department of Energy (DOE) proposes to fund, through a contract with Petroleum Consulting Services, Inc. of Canton, Ohio, the testing of the effectiveness of a non-water based hydraulic fracturing treatment to increase gas recovery from low-pressure, tight, fractured Devonian Shale formations. Although Devonian Shales are found in the Appalachian, Michigan, and Illinois Basins, testing will be done only in the dominant, historical five state area of established production. The objective of this proposed project is to assess the benefits of liquid carbon dioxide (CO 2 )/sand stimulations in the Devonian Shale. In addition, this project would evaluate the potential nondamaging (to the formation) properties of this unique fracturing treatment relative to the clogging or chocking of pores and fractures that act as gas flow paths to the wellbore in the target gas-producing zones of the formation. This liquid CO 2 /sand fracturing process is water-free and is expected to facilitate gas well cleanup, reduce the time required for post-stimulation cleanup, and result in improved production levels in a much shorter time than is currently experienced

  6. New Synthetic Methods for Hypericum Natural Products

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Insik [Iowa State Univ., Ames, IA (United States)

    2006-01-01

    Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.

  7. Chlorogenic Acid Biosynthesis Appears Linked with Suberin Production in Potato Tuber (Solanum tuberosum).

    Science.gov (United States)

    Valiñas, Matías Ariel; Lanteri, María Luciana; ten Have, Arjen; Andreu, Adriana Balbina

    2015-05-20

    Potato (Solanum tuberosum L.) is a good source of dietary antioxidants. Chlorogenic acid (CGA) and caffeic acid (CA) are the most abundant phenolic acid antioxidants in potato and are formed by the phenylpropanoid pathway. A number of CGA biosynthetic routes that involve hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase (HQT) and/or hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT) have been proposed, but little is known about their path in potato. CA production requires a caffeoyl shikimate esterase (CSE), and CA serves as a substrate of lignin precursor ferulic acid via the action of caffeic/5-hydroxyferulic acid O-methyltransferase (COMT I). CGA is precursor of caffeoyl-CoA and, via caffeoyl-CoA O-methyltransferase (CCoAOMT), of feruloyl-CoA. Feruloyl-CoA is required for lignin and suberin biosynthesis, crucial for tuber development. Here, metabolite and transcript levels of the mentioned and related enzymes, such as cinnamate 4-hydroxylase (C4H), were determined in the flesh and skin of fresh and stored tubers. Metabolite and transcript levels were higher in skin than in flesh, irrespective of storage. CGA and CA production appear to occur via p-coumaroyl-CoA, using HQT and CSE, respectively. HCT is likely involved in CGA remobilization toward suberin. The strong correlation between CGA and CA, the correspondence with C4H, HQT, CCoAOMT2, and CSE, and the negative correlation of HCT and COMT I in potato tubers suggest a major flux toward suberin.

  8. Learning Organic Chemistry Through Natural Products

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 10. Learning Organic Chemistry Through Natural Products Architectural Designs in Molecular Constructions. N R Krishnaswamy. Series Article Volume 1 Issue 10 October 1996 pp 37-43 ...

  9. Learning Organic Chemistry Through Natural Products

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 2. Learning Organic Chemistry Through Natural Products Determination of Absolute Stereochemistry. N R Krishnaswamy. Series Article Volume 1 Issue 2 February 1996 pp 40-46 ...

  10. Learning Organic Chemistry Through Natural Products

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 7. Learning Organic Chemistry Through Natural engine Products - Structure and Biological Functions. N R Krishnaswamy. Series Article Volume 1 Issue 7 July 1996 pp 23-30 ...

  11. Antifouling Activity of Marine Natural Products

    KAUST Repository

    Qian, Pei-Yuan; Xu, Sharon Ying

    2012-01-01

    for marine industries. Marine natural products have been considered as one of the most promising sources of antifouling compounds in recent years. In antifouling compound screening processes, bioassay systems often play most critical/vital roles in screening

  12. Learning Organic Chemistry Through Natural Products

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 12. Learning Organic Chemistry Through Natural Products - Architectural Designs in Molecular Constructions. N R Krishnaswamy. Volume 16 Issue 12 December 2011 pp 1287-1293 ...

  13. Synthesis of natural products of therapeutic significance

    Indian Academy of Sciences (India)

    system

    2015-11-07

    Nov 7, 2015 ... potential activity, while more natural products await the ... Treaty that prohibits commercial exploitation of Antarctic resources, the development of a synthetic strategy that allows the synthesis of palmerolide A and an array of its.

  14. Biotin in microbes, the genes involved in its biosynthesis, its biochemical role and perspectives for biotechnological production.

    Science.gov (United States)

    Streit, W R; Entcheva, P

    2003-03-01

    Biotin (vitamin H) is one of the most fascinating cofactors involved in central pathways in pro- and eukaryotic cell metabolism. Since its original discovery in 1901, research has led to the discovery of the complete biotin biosynthesis pathways in many different microbes and much work has been done on the highly intriguing and complex biochemistry of biotin biosynthesis. While humans and animals require several hundred micrograms of biotin per day, most microbes, plants and fungi appear to be able to synthesize the cofactor themselves. Biotin is added to many food, feed and cosmetic products, creating a world market of 10-30 t/year. However, the majority of the biotin sold is synthesized in a chemical process. Since the chemical synthesis is linked with a high environmental burden, much effort has been put into the development of biotin-overproducing microbes. A summary of biotin biosynthesis and its biological role is presented; and current strategies for the improvement of microbial biotin production using modern biotechnological techniques are discussed.

  15. Natural Products in the Discovery of Agrochemicals.

    Science.gov (United States)

    Loiseleur, Olivier

    2017-12-01

    Natural products have a long history of being used as, or serving as inspiration for, novel crop protection agents. Many of the discoveries in agrochemical research in the last decades have their origin in a wide range of natural products from a variety of sources. In light of the continuing need for new tools to address an ever-changing array of fungal, weed and insect pests, new agricultural practices and evolving regulatory requirements, the needs for new agrochemical tools remains as critical as ever. In that respect, nature continues to be an important source for novel chemical structures and biological mechanisms to be applied for the development of pest control agents. Here we review several of the natural products and their derivatives which contributed to shape crop protection research in past and present.

  16. Using Genomics for Natural Product Structure Elucidation.

    Science.gov (United States)

    Tietz, Jonathan I; Mitchell, Douglas A

    2016-01-01

    Natural products (NPs) are the most historically bountiful source of chemical matter for drug development-especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.

  17. Naturally Efficient Emitters: Luminescent Organometallic Complexes Derived from Natural Products

    Science.gov (United States)

    Zhang, Wen-Hua; Young, David J.

    2013-08-01

    Naturally occurring molecules offer intricate structures and functionality that are the basis of modern medicinal chemistry, but are under-represented in materials science. Herein, we review recent literature describing the use of abundant and relatively inexpensive, natural products for the synthesis of ligands for luminescent organometallic complexes used for organic light emitting diodes (OLEDs) and related technologies. These ligands are prepared from the renewable starting materials caffeine, camphor, pinene and cinchonine and, with the exception of caffeine, impart performance improvements to the emissive metal complexes and resulting OLED devices, with emission wavelengths that span the visible spectrum from blue to red. The advantages of these biologically-derived molecules include improved solution processibility and phase homogeneity, brighter luminescence, higher quantum efficiencies and lower turn-on voltages. While nature has evolved these carbon-skeletons for specific purposes, they also offer some intriguing benefits in materials science and technology.

  18. Psychoactive natural products: overview of recent developments

    Directory of Open Access Journals (Sweden)

    István Ujváry

    2014-03-01

    Full Text Available Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural products are also mentioned.

  19. Nature tourism: a sustainable tourism product

    Directory of Open Access Journals (Sweden)

    Violante Martínez Quintana

    2017-11-01

    Full Text Available Nature tourism has emerged in the tourism field as a result of a logical evolution in line with public policies and academic research. After negative outcomes from traditional models first raised the alarm, the entire sector has tried to foster local development based on models of responsibility and sustainability. This article revises key concepts of nature – based tourism and shows new tendencies and the perception of cultural landscapes that are seen as tourism products. Finally, it concludes by analysing new tendencies to foster alternative nature – based tourism. It also presents a planning proposal based on a responsible and sustainable tourism model to guarantee a sustainable tourism product within the natural and cultural heritage context.

  20. Review: Natural products from Genus Selaginella (Selaginellaceae

    Directory of Open Access Journals (Sweden)

    AHMAD DWI SETYAWAN

    2011-01-01

    Full Text Available Setyawan AD. 2011. Natural products from Genus Selaginella (Selaginellaceae. Nusantara Bioscience 3: 44-58. Selaginella is a potent medicinal-stuff, which contains diverse of natural products such as alkaloid, phenolic (flavonoid, and terpenoid. This species is traditionally used to cure several diseases especially for wound, after childbirth, and menstrual disorder. Biflavonoid, a dimeric form of flavonoids, is the most valuable natural products of Selaginella, which constituted at least 13 compounds, namely amentoflavone, 2',8''-biapigenin, delicaflavone, ginkgetin, heveaflavone, hinokiflavone, isocryptomerin, kayaflavone, ochnaflavone, podocarpusflavone A, robustaflavone, sumaflavone, and taiwaniaflavone. Ecologically, plants use biflavonoid to response environmental condition such as defense against pests, diseases, herbivory, and competitions; while human medically use biflavonoid especially for antioxidant, anti-inflammatory, and anti carcinogenic. Selaginella also contains valuable disaccharide, namely trehalose that has long been known for protecting from desiccation and allows surviving severe environmental stress. The compound has very prospects as molecular stabilizer in the industries based bioresources.

  1. Natural gas and production of electricity

    International Nuclear Information System (INIS)

    Defago, E.

    2005-01-01

    The forthcoming power supply shortage in Switzerland due to increasing consumption is discussed, as are the possibilities for securing the future supply. Today, the main sources are hydroelectric (roughly 55 %) and nuclear (40 %) power. The share of electricity from natural gas amounts to only 1.4 %. The possibilities of further economic production of hydropower are practically exhausted. Therefore, further electric power has to be either imported or generated from other energy sources (renewable, nuclear, fossil) in the country itself. Due to the low acceptance of nuclear energy and the limited potential of renewable energy sources, natural gas is the most favoured candidate. The advantages of distributed production in cogeneration plants are compared with the centralized production in larger plants using combined cycles. Finally, a project currently under development is presented: an existing thermal power plant fueled with heavy fuel oil shall be refurbished and converted to natural gas as the new fuel

  2. Biosynthesis of gold and silver nanoparticles by natural precursor clove and their functionalization with amine group

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Ashwani Kumar; Talat, Mahe [Banaras Hindu University, Nanoscience and Nanotechnology Unit, Department of Physics (India); Singh, D. P. [Southern Illinois University Carbondale, Department of Physics (United States); Srivastava, O. N., E-mail: hepons@yahoo.co [Banaras Hindu University, Nanoscience and Nanotechnology Unit, Department of Physics (India)

    2010-06-15

    We report a simple and cost effective way for synthesis of metallic nanoparticles (Au and Ag) using natural precursor clove. Au and Ag nanoparticles have been synthesized by reducing the aqueous solution of AuCl{sub 4} and AgNO{sub 3} with clove extract. One interesting aspect here is that reduction time is quite small (few minutes instead of hours as compared to other natural precursors). We synthesized gold and silver nanoparticles of different shape and size by varying the ratio of AuCl{sub 4} and AgNO{sub 3} with respect to clove extract, where the dominant component is eugenol. The evolution of Au and Ag nanoparticles from the reduction of different ratios of AuCl{sub 4} and AgNO{sub 3} with optimised concentration of the clove extract has been evaluated through monitoring of surface plasmon behaviour as a function of time. The reduction of AuCl{sub 4} and AgNO{sub 3} by eugenol is because of the inductive effect of methoxy and allyl groups which are present at ortho and para positions of proton releasing -OH group as two electrons are released from one molecule of eugenol. This is followed by the formation of resonating structure of the anionic form of eugenol. The presence of methoxy and allyl groups has been confirmed by FTIR. To the best of our knowledge, use of clove as reducing agent, the consequent very short time (minutes instead of hours and without any scavenger) and the elucidation of mechanism of reduction based on FTIR analysis has not been attempted earlier.

  3. Releasing intracellular product to prepare whole cell biocatalyst for biosynthesis of Monascus pigments in water-edible oil two-phase system.

    Science.gov (United States)

    Hu, Minglue; Zhang, Xuehong; Wang, Zhilong

    2016-11-01

    Selective releasing intracellular product in Triton X-100 micelle aqueous solution to prepare whole cell biocatalyst is a novel strategy for biosynthesis of Monascus pigments, in which cell suspension culture exhibits some advantages comparing with the corresponding growing cell submerged culture. In the present work, the nonionic surfactant Triton X-100 was successfully replaced by edible plant oils for releasing intracellular Monascus pigments. High concentration of Monascus pigments (with absorbance nearly 710 AU at 470 nm in the oil phase, normalized to the aqueous phase volume approximately 142 AU) was achieved by cell suspension culture in peanut oil-water two-phase system. Furthermore, the utilization of edible oil as extractant also fulfills the demand for application of Monascus pigments as natural food colorant.

  4. Natural gas product and strategic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Layne, A.W.; Duda, J.R.; Zammerilli, A.M.

    1993-12-31

    Product and strategic analysis at the Department of Energy (DOE)/Morgantown Energy Technology Center (METC) crosscuts all sectors of the natural gas industry. This includes the supply, transportation, and end-use sectors of the natural-gas market. Projects in the Natural Gas Resource and Extraction supply program have been integrated into a new product focus. Product development facilitates commercialization and technology transfer through DOE/industry cost-shared research, development, and demonstration (RD&D). Four products under the Resource and Extraction program include Resource and Reserves; Low Permeability Formations; Drilling, Completion, and Stimulation: and Natural Gas Upgrading. Engineering process analyses have been performed for the Slant Hole Completion Test project. These analyses focused on evaluation of horizontal-well recovery potential and applications of slant-hole technology. Figures 2 and 3 depict slant-well in situ stress conditions and hydraulic fracture configurations. Figure 4 presents Paludal Formation coal-gas production curves used to optimize the hydraulic fracture design for the slant well. Economic analyses have utilized data generated from vertical test wells to evaluate the profitability of horizontal technology for low-permeability formations in Yuma County, Colorado, and Maverick County, Texas.

  5. Simple biosynthesis of zinc oxide nanoparticles using nature's source, and it's in vitro bio-activity

    Science.gov (United States)

    Zare, Elham; Pourseyedi, Shahram; Khatami, Mehrdad; Darezereshki, Esmaeel

    2017-10-01

    Nanoparticles with antimicrobial activity, especially as a new class of biomedical materials for use in increasing the level of public health in daily life have emerged. In this study, green synthesis of zinc oxide) ZnO(nanoparticles was studied by Cuminum cyminum (cumin) as novel natural source and zinc nitrate [Zn(NO3)2] as Zn2+ source. The results showed that parameters such as concentration, time, temperature and pH have a direct impact on the synthesis of zinc nanoparticles and change in any of the factors causing the change in the process of synthesis. The properties of synthesized nanoparticles were examined by UV-visible Spectrophotometer, X-ray diffraction spectroscopy and transmission electron microscopy (TEM). The UV-visible spectroscopy presented the absorption peak in the range of 370 nm. Transmission electron microscopy images of synthesized nanoparticles are mainly spherical or oval with an average size of about 7 nm. The effect of antimicrobial nanoparticles calculated using disk diffusion method and broth MIC and MBC in different strains of bacteria, which showed that gram positive and negative were sensitive to zinc oxide nanoparticles. The sensitivity of gram-negative bacteria was more.

  6. Natural products from microbes associated with insects

    DEFF Research Database (Denmark)

    Beemelmanns, Christine; Guo, Huijuan; Rischer, Maja

    2016-01-01

    Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We...

  7. Natural products – learning chemistry from plants

    NARCIS (Netherlands)

    Staniek, A.; Bouwmeester, H.J.; Fraser, P.D.; Kayser, O.; Martens, S.; Tissier, A.; Krol, van der A.R.; Wessjohann, L.; Warzecha, H.

    2014-01-01

    Plant natural products (PNPs) are unique in that they represent a vast array of different structural features, ranging from relatively simple molecules to very complex ones. Given the fact that many plant secondary metabolites exhibit profound biological activity, they are frequently used as

  8. Learning Organic Chemistry Through Natural Products -12 ...

    Indian Academy of Sciences (India)

    Higher Learning. Generations of students would vouch for the fact that he has the uncanny ability to present the chemistry of natural products logically and with feeling. The most interesting chemical aspect of a molecule is its. reactivHy pattern. NR Krishnaswamy. In this part of the series, dynamic organic chemistry and.

  9. Learning Organic Chemistry Through Natural Products

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 5. Learning Organic Chemistry Through Natural Products From Molecular and Electronic Structures to Reactivity. N R Krishnaswamy. Series Article Volume 1 Issue 5 May 1996 pp 12-18 ...

  10. Flow chemistry syntheses of natural products.

    Science.gov (United States)

    Pastre, Julio C; Browne, Duncan L; Ley, Steven V

    2013-12-07

    The development and application of continuous flow chemistry methods for synthesis is a rapidly growing area of research. In particular, natural products provide demanding challenges to this developing technology. This review highlights successes in the area with an emphasis on new opportunities and technological advances.

  11. Marine Natural Products as Prototype Agrochemical Agents

    Science.gov (United States)

    Peng, Jiangnan; Shen, Xiaoyu; El Sayed, Khalid A.; Dunbar, D. C Harles; Perry, Tony L.; Wilkins, Scott P.; Hamann, Mark T.; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A.

    2016-01-01

    In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents. PMID:12670165

  12. Plants as natural antioxidants for meat products

    Science.gov (United States)

    Tomović, V.; Jokanović, M.; Šojić, B.; Škaljac, S.; Ivić, M.

    2017-09-01

    The meat industry is demanding antioxidants from natural sources to replace synthetic antioxidants because of the negative health consequences or beliefs regarding some synthetic ones. Plants materials provide good alternatives. Spices and herbs, generally used for their flavouring characteristics, can be added to meat products in various forms: whole, ground, or as isolates from their extracts. These natural antioxidants contain some active compounds, which exert antioxidative potential in meat products. This antioxidant activity is most often due to phenolic acids, phenolic diterpenes, flavonoids and volatile oils. Each of these compounds often has strong H-donating activity, thus making them extremely effective antioxidants; some compounds can chelate metals and donate H to oxygen radicals, thus slowing oxidation via two mechanisms. Numerous studies have demonstrated the efficacy of natural antioxidants when used in meat products. Based on this literature review, it can be concluded that natural antioxidants are added to fresh and processed meat and meat products to delay, retard, or prevent lipid oxidation, retard development of off-flavours (rancidity), improve colour stability, improve microbiological quality and extend shelf-life, without any damage to the sensory or nutritional properties.

  13. The Rakicidin Family of Anticancer Natural Products

    DEFF Research Database (Denmark)

    Tsakos, Michail; Jacobsen, Kristian Mark; Yu, Wanwan

    2016-01-01

    Rakicidin A is a prominent member of a small class of macrocyclic lipodepsipeptide natural products that contain an electrophilic 4- amido-2,4-pentadienoate (APD) functionality. Rakicidin A displays selective growth inhibitory activity against hypoxic cancer cells as well as imatinib...

  14. Chocolate: A Marvelous Natural Product of Chemistry

    Science.gov (United States)

    Tannenbaum, Ginger

    2004-01-01

    The study of chocolate, a natural product, can be beneficial for the chemistry students as they ask frequently about the relevancy of their chemistry classes. The history of chocolate, its chemical and physical changes during processing, its composition, different crystalline forms, tempering and its viscosity are discussed.

  15. Alternative solvents for natural products extraction

    CERN Document Server

    Chemat, Farid

    2014-01-01

    This book presents a complete picture of the current state-of-the-art in alternative and green solvents used for laboratory and industrial natural product extraction in terms of the latest innovations, original methods and safe products. It provides the necessary theoretical background and details on extraction, techniques, mechanisms, protocols, industrial applications, safety precautions and environmental impacts. This book is aimed at professionals from industry, academicians engaged in extraction engineering or natural product chemistry research, and graduate level students. The individual chapters complement one another, were written by respected international researchers and recognized professionals from the industry, and address the latest efforts in the field. It is also the first sourcebook to focus on the rapid developments in this field.

  16. Chapter 7. Cloning and analysis of natural product pathways.

    Science.gov (United States)

    Gust, Bertolt

    2009-01-01

    The identification of gene clusters of natural products has lead to an enormous wealth of information about their biosynthesis and its regulation, and about self-resistance mechanisms. Well-established routine techniques are now available for the cloning and sequencing of gene clusters. The subsequent functional analysis of the complex biosynthetic machinery requires efficient genetic tools for manipulation. Until recently, techniques for the introduction of defined changes into Streptomyces chromosomes were very time-consuming. In particular, manipulation of large DNA fragments has been challenging due to the absence of suitable restriction sites for restriction- and ligation-based techniques. The homologous recombination approach called recombineering (referred to as Red/ET-mediated recombination in this chapter) has greatly facilitated targeted genetic modifications of complex biosynthetic pathways from actinomycetes by eliminating many of the time-consuming and labor-intensive steps. This chapter describes techniques for the cloning and identification of biosynthetic gene clusters, for the generation of gene replacements within such clusters, for the construction of integrative library clones and their expression in heterologous hosts, and for the assembly of entire biosynthetic gene clusters from the inserts of individual library clones. A systematic approach toward insertional mutation of a complete Streptomyces genome is shown by the use of an in vitro transposon mutagenesis procedure.

  17. [Sugar Chain Construction of Functional Natural Products Using Plant Glucosyltransferases].

    Science.gov (United States)

    Mizukami, Hajime

    2015-01-01

    Plant secondary product glycosyltransferases belong to family 1 of the glycosyltransferase superfamily and mediate the transfer of a glycosyl residue from activated nucleotide sugars to lipophilic small molecules, thus affecting the solubility, stability and pharmacological activities of the sugar-accepting compounds. The biotechnological application of plant glycosyltransferases in glycoside synthesis has attracted attention because enzymatic glycosylation offers several advantages over chemical methods, including (1) avoiding the use of harsh conditions and toxic catalysts, (2) providing strict control of regio-and stereo-selectivity and (3) high efficiency. This review describes the in vivo and in vitro glycosylation of natural organic compounds using glycosyltransferases, focusing on our investigation of enzymatic synthesis of curcumin glycosides. Our current efforts toward functional characterization of some glycosyltransferases involved in the biosynthesis of iridoids and crocin, as well as in the sugar chain elongation of quercetin glucosides, are described. Finally, I describe the relationship of the structure of sugar chains and the intestinal absorption which was investigated using chemoenzymatically synthesized quercetin glycosides.

  18. Unraveling the mystery of natural rubber biosynthesis. Part II. Composition and growth of in vitro natural rubber using high-resolution size exclusion chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Cheng Ching K. [Univ. of Akron, OH (United States); Barkakaty, Balaka [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Puskas, Judit E. [Univ. of Akron, OH (United States); Xie, Wenshuang [The Ohio State Univ., Wooster, OH (United States); Cornish, Katrina [The Ohio State Univ., Wooster, OH (United States); Peruch, Federic [Univ. of Bordeaux, Pessac Cedex (France); Deffieux, Alain [Univ. of Bordeaux, Pessac Cedex (France)

    2014-09-01

    The superior properties of natural rubber (cis-1,4-polyisoprene [NR]) are a function of its structure and composition, properties that still remain a mystery and that are irreplaceable by any synthetic rubber. NR from guayule (Parthenium argentatum) has been gaining special interest for its hypoallergenic properties while maintaining superior mechanical properties that are commonly associated with the Brazilian rubber tree (Hevea brasiliensis), the most common source of NR. Techniques exist to isolate washed rubber particles (WRPs) that contain enzymatically active rubber transferase, to study NR biosynthesis, and previous work on the in vitroNRgrowth in Hevea has demonstrated the presence of around 50wt%of a low molecular weight ([MW], Mn <10 000 g/mol) fraction. Structural and compositional analyses of this low MW fraction in Hevea are challenging due to the high protein content. Here, we discuss the analysis and composition of guayule latex and WRPs using high-resolution Size Exclusion Chromatography. We also discuss the composition of the soluble fraction of inactive guayule latex using matrix-assisted laser desorption ionization/time of flight mass spectrometry.

  19. Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.

    Science.gov (United States)

    Niu, Guoqing; Tan, Huarong

    2015-02-01

    The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics. Copyright © 2014. Published by Elsevier Ltd.

  20. The expanding universe of alkaloid biosynthesis.

    Science.gov (United States)

    De Luca, V; Laflamme, P

    2001-06-01

    Characterization of many of the major gene families responsible for the generation of central intermediates and for their decoration, together with the development of large genomics and proteomics databases, has revolutionized our capability to identify exotic and interesting natural-product pathways. Over the next few years, these tools will facilitate dramatic advances in our knowledge of the biosynthesis of alkaloids, which will far surpass that which we have learned in the past 50 years. These tools will also be exploited for the rapid characterization of regulatory genes, which control the development of specialized cell factories for alkaloid biosynthesis.

  1. Regulation of natural health products in Canada.

    Science.gov (United States)

    Smith, Alysyn; Jogalekar, Sumedha; Gibson, Adam

    2014-12-02

    In Canada, all natural health products (NHPs) are regulated by Health Canada (HC) under the Food and Drugs Act and the Natural Health Product Regulations. All authorized products undergo pre-market assessment for safety, efficacy and quality and the degree of pre-market oversight varies depending on the risk of the product. In Canada, over 70,000 products have been authorized for sale and over 2000 sites have been licensed to produce NHPs. In the management of NHPs on the Canadian market, HC employs a number of active and collaborative methods to address the most common issues such as contamination, adulteration and deceptive or misleading advertising practices. HC is currently evolving its approaches to NHPs to recognize them as part of the larger group of health products available without a prescription. As such, the regulatory responsibility for all over-the-counter (OTC) drugs, including non-prescription drugs and NHPs, has been transferred to a single federal division. As a result of this transition a number of benefits are being realized with respect to government efficiency, clarity for industry, support for new innovations and consolidated government interactions with the Canadian market. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Recent advances in combinatorial biosynthesis for drug discovery

    Directory of Open Access Journals (Sweden)

    Sun H

    2015-02-01

    Full Text Available Huihua Sun,1,* Zihe Liu,1,* Huimin Zhao,1,2 Ee Lui Ang1 1Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, Singapore; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA *These authors contributed equally to this work Abstract: Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1 precursor-directed biosynthesis; 2 enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3 pathway-level recombination. Recent examples of combinatorial biosynthesis employing these

  3. Heme biosynthesis and its regulation : Toward understanding and improvement of heme biosynthesis in filamentous fungi.

    NARCIS (Netherlands)

    S. de Weert; P.J. Punt; Christien Lokman; C.A. van den Hondel; A.C. Franken; A.F. Ram

    2011-01-01

    Heme biosynthesis in fungal host strains has acquired considerable interest in relation to the production of secreted heme-containing peroxidases. Class II peroxidase enzymes have been suggested as eco-friendly replacements of polluting chemical processes in industry. These peroxidases are naturally

  4. Heme biosynthesis and its regulation: Towards understanding and improvement of heme biosynthesis in filamentous fungi

    NARCIS (Netherlands)

    Franken, A.C.W.; Lokman, B.C.; Ram, A.F.J.; Punt, P.J.; Hondel, C.A.M.J.J. van den; Weert, S. de

    2011-01-01

    Heme biosynthesis in fungal host strains has acquired considerable interest in relation to the production of secreted heme-containing peroxidases. Class II peroxidase enzymes have been suggested as eco-friendly replacements of polluting chemical processes in industry. These peroxidases are naturally

  5. The enzymology of polyether biosynthesis.

    Science.gov (United States)

    Liu, Tiangang; Cane, David E; Deng, Zixin

    2009-01-01

    Polyether ionophore antibiotics are a special class of polyketides widely used in veterinary medicine, and as food additives in animal husbandry. In this article, we review current knowledge about the mechanism of polyether biosynthesis, and the genetic and biochemical strategies used for its study. Several clear differences distinguish it from traditional type I modular polyketide biosynthesis: polyether backbones are assembled by modular polyketide synthases but are modified by two key enzymes, epoxidase and epoxide hydrolase, to generate the product. All double bonds involved in the oxidative cyclization in the polyketide backbone are of E geometry. Chain release in the polyether biosynthetic pathway requires a special type II thioesterase which specifically hydrolyzes the polyether thioester. All these discoveries should be very helpful for a deep understanding of the biosynthetic mechanism of this class of important natural compounds, and for the targeted engineering of polyether derivatives.

  6. Chemical Biology of Microbial Anticancer Natural Products

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Gotfredsen, Charlotte Held

    than 100 years. New natural products (NPs) are continually discovered and with the increase in selective biological assays, previously described compounds often also display novel bioactivities, justifying their presence in novel screening efforts. Screening and discovery of compounds with activity...... towards chronic lymphocytic leukemia (CLL) cells is crucial since CLL is considered as an incurable disease. To discover novel agents that targets CLL cells is complicated. CLL cells rapidly undergo apoptosis in vitro when they are removed from their natural microenvironment, even though they are long...

  7. Manipulation Of Lignin Biosynthesis To Maximize Ethanol Production From Populus Feedstocks

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Clint Chapple; Dr. Rick Lindroth; Dr. Burce Dien; Dr. Glen Stanosz; Dr. Alex Wiedenhoeft; Dr. Fu Zhao; Dr. Duane Wegener; Dr. Janice Kelly; Dr. Leigh Raymond; Dr. Wallace Tyner

    2012-05-15

    Our research focuses on transgenic strategies for modifying lignification to improve biomass quality, without leading to deleterious effects on plant performance. In order to accomplish this objective, we designed molecular strategies and selected appropriate transgenes for manipulating the expression of lignification-associated genes; we generated poplar engineered for altered lignin content and/or monomer composition, and field-tested them for fitness; we analyzed the impact of these transgenic strategies on metabolism in general and lignin biosynthesis in particular; and evaluated the ease with which cell wall deconstruction can be accomplished using both chemical and enzymatic means using wild-type and high syringyl poplar.

  8. Utilization of Natural Products as Functional Feed

    Directory of Open Access Journals (Sweden)

    Stella Magdalena

    2013-03-01

    Full Text Available The use of antibiotics as feed additive improves performance in livestock. However, scientific data related to the use of antibiotics in feed merge spreading of bacterial resistance in animal and human bodies, therefore the usage of antibiotics in animal production is restricted. This condition raise the utilization of natural antibiotic as functional feed such as phytogenics (essential oil, flavonoid, saponin, and tannin, enzyme, probiotic, and prebiotic to improve the livestock’s performance, quality, and health. Functional feeds increase profitability in animal husbandry production and its use is feeds are expected to be functional foods that may have positive effects in human nutrition.

  9. Natural Products Combating Neurodegeneration: Parkinson's Disease.

    Science.gov (United States)

    Solayman, Md; Islam, Md Asiful; Alam, Fahmida; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua

    2017-01-01

    Parkinson's disease (PD) is characterized by neurodegeneration and a progressive functional impairment of the midbrain nigral dopaminergic neurons. The cause remains unknown; however, several pathological processes and central factors, such as protein aggregation, mitochondrial dysfunction, iron accumulation, neuroinflammation and oxidative stress, have been reported. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors and anticholinergics to replace DA. When drug therapy is not satisfactory, surgical treatments are recommended. Unfortunately, the existing conventional strategies that target PD are associated with numerous side effects and possess an economic burden. Therefore, novel therapeutic approaches that regulate the pathways leading to neuronal death and dysfunction are necessary. For many years, nature has provided the primary resource for the discovery of potential therapeutic agents. Remarkably, many natural products from medicinal plants, fruits and vegetables have been demonstrated to be efficacious anti-Parkinson agents. These products possess neuroprotective properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding iron accumulation, protein misfolding and the maintenance of proteasomal degradation, as well as mitochondrial homeostasis. The aim of this review is to report the available anti-Parkinson agents based on natural products and delineate their therapeutic actions, which act on various pathways. Overall, this review emphasizes the types of natural products that are potential future resources in the treatment of PD as novel regimens or supplementary agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. The chemistry of isoindole natural products

    OpenAIRE

    Speck, Klaus; Magauer, Thomas

    2013-01-01

    Summary This review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples...

  11. Utilization of Natural Products as Functional Feed

    OpenAIRE

    Stella Magdalena; Natadiputri G H; Nailufar; Purwadaria T

    2013-01-01

    The use of antibiotics as feed additive improves performance in livestock. However, scientific data related to the use of antibiotics in feed merge spreading of bacterial resistance in animal and human bodies, therefore the usage of antibiotics in animal production is restricted. This condition raise the utilization of natural antibiotic as functional feed such as phytogenics (essential oil, flavonoid, saponin, and tannin), enzyme, probiotic, and prebiotic to improve the livestock’s performan...

  12. Natural cold pressed oils as cosmetic products

    Directory of Open Access Journals (Sweden)

    Małgorzata Ligęza

    2016-12-01

    Full Text Available Background. It seems that patients may ask general practitioners about natural cosmetics applied on the skin regarding their safety and suitability. Objectives. The aim of the study was to analyze natural cold pressed oils as potential cosmetic products. Material and methods. Cold pressed oils obtained from selected seeds and fruit stones were analyzed, including: chokeberry seed oil, blackcurrant seed oil, elderberry seed oil, raspberry seed oil, apricot seed oil, tomato seed oil, strawberry seed oil, broccoli seed oil, Nigella sativa seed oil, hemp oil, safflower seed oil, Silybum marianum seed oil and coconut oil. 80 adult volunteers assessed the cosmetic properties of the analyzed oils. Each of the volunteers tested 2 to 4 different oils, by applying them on the skin. In addition, patch tests with all analyzed oils were performed on 23 individuals. Results. The majority of tested oils were positively evaluated by the participants: in the opinion of the participants, oil extracted from safflower had the best appearance (100% positive opinions, coconut oil had the best smell (70% positive opinions, while black currant seed oil showed the best absorbency (85% positive opinions. No irritation was observed within the analyzed product group, albeit one allergic reaction to apricot seed oil was observed with patch testing. Conclusions . Based on the achieved results, it could be suggested that natural cold pressed oils can be applied to the skin as cosmetics. Our observations may be helpful for general practitioners when choosing natural cosmetics.

  13. Genome engineering for microbial natural product discovery.

    Science.gov (United States)

    Choi, Si-Sun; Katsuyama, Yohei; Bai, Linquan; Deng, Zixin; Ohnishi, Yasuo; Kim, Eung-Soo

    2018-03-03

    The discovery and development of microbial natural products (MNPs) have played pivotal roles in the fields of human medicine and its related biotechnology sectors over the past several decades. The post-genomic era has witnessed the development of microbial genome mining approaches to isolate previously unsuspected MNP biosynthetic gene clusters (BGCs) hidden in the genome, followed by various BGC awakening techniques to visualize compound production. Additional microbial genome engineering techniques have allowed higher MNP production titers, which could complement a traditional culture-based MNP chasing approach. Here, we describe recent developments in the MNP research paradigm, including microbial genome mining, NP BGC activation, and NP overproducing cell factory design. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Alternative Fuels Data Center: Conventional Natural Gas Production

    Science.gov (United States)

    Conventional Natural Gas Production to someone by E-mail Share Alternative Fuels Data Center : Conventional Natural Gas Production on Facebook Tweet about Alternative Fuels Data Center: Conventional Natural Gas Production on Twitter Bookmark Alternative Fuels Data Center: Conventional Natural Gas Production

  15. Natural gas production from underground nuclear explosions

    Energy Technology Data Exchange (ETDEWEB)

    1965-01-01

    A remote location in Rio Arriba County, NW. New Mexico, is being considered as the site for an experiment in the use of a nuclear explosive to increase production from a natural gas field. A feasibility study has been conducted by the El Paso Natural Gas Co., the U.S. Atomic Energy commission, and the U.S. Bureau of Mines. As presently conceived, a nuclear explosive would be set in an emplacement hole and detonated. The explosion would create a cylinder or ''chimney'' of collapsed rock, and a network of fractures extending beyond the chimney. The fractures are the key effect. These would consist of new fractures, enlargement of existing ones, and movement along planes where strata overlap. In addition, there are a number of intangible but important benefits that could accrue from the stimulating effect. Among these are the great increase in recoverable reserves and the deliverability of large volumes of gas during the periods of high demand. It is believed that this type of well stimulation may increase the total gas production of these low permeability natural gas fields by about 7 times the amounts now attainable.

  16. Natural products as potential anticonvulsants: caffeoylquinic acids.

    Science.gov (United States)

    Kim, Hyo Geun; Oh, Myung Sook

    2012-03-01

    Current anticonvulsant therapies are generally directed at symptomatic treatment by suppressing excitability within the brain. Consequently, they have adverse effects such as cognitive impairment, dependence, and abuse. The need for more effective and less toxic anticonvulsants has generated renewed interest in natural products for the treatment of convulsions. Caffeoylquinic acids (CQs) are naturally occurring phenolic acids that are distributed widely in plants. There has been increasing interest in the biological activities of CQs in diseases of the central nervous system. In this issue, Nugroho et al. give evidence for the anticonvulsive effect of a CQ-rich extract from Aster glehni Franchet et Sckmidt. They optimized the extract solvent conditions, resulting in high levels of CQs and peroxynitrite-scavenging activity. Then, they investigated the sedative and anticonvulsive effects in pentobarbital- and pentylenetetrazole-induced models in mice. The CQ-rich extract significantly inhibited tonic convulsions as assessed by onset time, tonic extent, and mortality. They suggested that the CQ-rich extract from A. glehni has potential for treating convulsions. This report provides preclinical data which may be used for the development of anticonvulsants from natural products.

  17. Ornithine Decarboxylase-Mediated Production of Putrescine Influences Ganoderic Acid Biosynthesis by Regulating Reactive Oxygen Species in Ganoderma lucidum.

    Science.gov (United States)

    Wu, Chen-Gao; Tian, Jia-Long; Liu, Rui; Cao, Peng-Fei; Zhang, Tian-Jun; Ren, Ang; Shi, Liang; Zhao, Ming-Wen

    2017-10-15

    Putrescine is an important polyamine that participates in a variety of stress responses. Ornithine decarboxylase (ODC) is a key enzyme that catalyzes the biosynthesis of putrescine. A homolog of the gene encoding ODC was cloned from Ganoderma lucidum In the ODC -silenced strains, the transcript levels of the ODC gene and the putrescine content were significantly decreased. The ODC -silenced strains were more sensitive to oxidative stress. The content of ganoderic acid was increased by approximately 43 to 46% in the ODC -silenced strains. The content of ganoderic acid could be recovered after the addition of exogenous putrescine. Additionally, the content of reactive oxygen species (ROS) was significantly increased by approximately 1.3-fold in the ODC -silenced strains. The ROS content was significantly reduced after the addition of exogenous putrescine. The gene transcript levels and the activities of four major antioxidant enzymes were measured to further explore the effect of putrescine on the intracellular ROS levels. Further studies showed that the effect of the ODC-mediated production of putrescine on ROS might be a factor influencing the biosynthesis of ganoderic acid. Our study reports the role of putrescine in large basidiomycetes, providing a basis for future studies of the physiological functions of putrescine in microbes. IMPORTANCE It is well known that ODC and the ODC-mediated production of putrescine play an important role in resisting various environmental stresses, but there are few reports regarding the mechanisms underlying the effect of putrescine on secondary metabolism in microorganisms, particularly in fungi. G. lucidum is gradually becoming a model organism for studying environmental regulation and metabolism. In this study, a homolog of the gene encoding ODC was cloned in Ganoderma lucidum We found that the transcript level of the ODC gene and the content of putrescine were significantly decreased in the ODC -silenced strains. The content of

  18. DasR is a pleiotropic regulator required for antibiotic production, pigment biosynthesis, and morphological development in Saccharopolyspora erythraea.

    Science.gov (United States)

    Liao, Cheng-Heng; Xu, Ya; Rigali, Sébastien; Ye, Bang-Ce

    2015-12-01

    The GntR-family transcription regulator, DasR, was previously identified as pleiotropic, controlling the primary amino sugar N-acetylglucosamine (GlcNAc) and chitin metabolism in Saccharopolyspora erythraea and Streptomyces coelicolor. Due to the remarkable regulatory impact of DasR on antibiotic production and development in the model strain of S. coelicolor, we here identified and characterized the role of DasR to secondary metabolite production and morphological development in industrial erythromycin-producing S. erythraea. The physiological studies have shown that a constructed deletion of dasR in S. erythraea resulted in antibiotic, pigment, and aerial hyphae production deficit in a nutrient-rich condition. DNA microarray assay, combined with quantitative real-time reverse transcription PCR (qRT-PCR), confirmed these results by showing the downregulation of the genes relating to secondary metabolite production in the dasR null mutant. Notably, electrophoretic mobility shift assays (EMSA) showed DasR as being the first identified regulator that directly regulates the pigment biosynthesis rpp gene cluster. In addition, further studies indicated that GlcNAc, the major nutrient signal of DasR-responsed regulation, blocked secondary metabolite production and morphological development. The effects of GlcNAc were shown to be caused by DasR mediation. These findings demonstrated that DasR is an important pleiotropic regulator for both secondary metabolism and morphological development in S. erythraea, providing new insights for the genetic engineering of S. erythraea with increased erythromycin production.

  19. Structure elucidation of secondary natural products

    International Nuclear Information System (INIS)

    Seger, C.

    2001-06-01

    The presented thesis deals with the structure elucidation of secondary natural products. Most of the compounds under investigation were terpenes, especially triterpenes, alkaloids and stilbenoids. Besides characterizing a multitude of already known and also new compounds, it was possible to detect and correct wrongly assigned literature data. The methodological aspect of this thesis lies - beside in the utilization of modern 2D NMR spectroscopy - in the evaluation of computer assisted structure elucidation (CASE) techniques in the course of spectroscopy supported structure elucidation processes. (author)

  20. Appreciation of symmetry in natural product synthesis.

    Science.gov (United States)

    Bai, Wen-Ju; Wang, Xiqing

    2017-12-13

    Covering: 2012 to June 2017This review aims to show that complex natural product synthesis can be streamlined by taking advantage of molecular symmetry. Various strategies to construct molecules with either evident or hidden symmetry are illustrated. Insights regarding the origins and adjustments of these strategies as well as inspiring new methodological developments are deliberated. When a symmetric strategy fails, the corresponding reason is analysed and an alternative approach is briefly provided. Finally, the importance of exploiting molecular symmetry and future research directions are discussed.

  1. Natural gas: reserves keep ahead of production

    Energy Technology Data Exchange (ETDEWEB)

    Hough, G V

    1983-08-01

    World production of natural gas in 1982 fell only 1.6% below 1981 levels, while proven recoverable reserves were up by 3.6% for a total of 3.279 quadrillion CF, which is 32.4% higher than had been estimated in 1978. Gas consumption, however, has experienced greater changes, with most of the industrialized countries (except for Japan) reporting declines in gas demand resulting from falling oil prices, reduced energy demand, and a slack world economy. Although gas seems to be holding its own in energy markets, further progress will not be easy to achieve.

  2. Natural products as radiation response modifiers

    International Nuclear Information System (INIS)

    Colin Seymour; Carmel Mothersill

    2007-01-01

    Complete text of publication follows. Protection of cells and organisms against low doses of radiation is a complex issue which must be considered at the level of cells, tissues and organisms. 'Protection' at one level, for example, prevention of cell death, may be adverse at another level, if it allows a damaged cell to survive and form a malignant tumour. Conversely, death of a cell carrying damage can be protective for the organism if it eliminates a damaged cell. Thus, it is important to understand the mechanisms involved in protection against radiation damage at several hierarchical levels. The use of natural products as radiation response modifiers is very attractive. Many of these compounds are readily available and their function and pharmacology is well understood. Some derive from venoms or natural defenses and are currently used in medicine, others include vitamins, antioxidants or cofactors, which are tried and tested nutritional supplements. Radiation effects may be targeted or untargeted. Radiation may interact directly within a cell causing a direct DNA lesion or it may elicit a bystander response from the irradiated cell. A bystander effect is produced when the irradiated cell apparently exhibits no damage from the radiation, but passes on a biochemical signal which induces neighbouring cells to apoptose or undergo a number of other responses usually associated with irradiation such as mutation induction, transformation, induction of ROS responses etc.. Effects induced in progeny of non-targeted cells in receipt of bystander signals include genetic instability, mini and microsatellite mutations and carcinogenesis. A key characteristic of these non targeted effects is that they occur at very low acute doses (of the order of 5mGy) and saturate so that effective prevention requires an agent which can effectively shut off the mechanism. While the mechanism is not fully known, it is thought to involve signals from irradiated cells communicating via

  3. Amorfrutins are potent antidiabetic dietary natural products

    Science.gov (United States)

    Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

    2012-01-01

    Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006

  4. Yoghurt enrichment with natural bee farming products

    Directory of Open Access Journals (Sweden)

    N. Lomova

    2015-05-01

    Full Text Available Introduction. Bee pollen is a unique and unparalleled natural bioactive substances source. Using it in conjunction with the popular functional fermented milk product -yogurt will expand its product range and increase the biological value. Materials and Methods. Dried bee pollen’s moisture determination was made by gravimetry methods, based on the sample weight loss due to desiccation, until constant weight was reached.Test and control yogurt samples were studied by applying standard techniques for milk and milk products set forth in the regulations of Ukraine. Results and discussion. It is found that bee pollen pellet drying to a moisture content of 2 -4%, increases the flow rate of powder almost by 90%. The sample having moisture content of 2% will have a bulk density exceeding 12.5% compared to the sample having moisture content of 10%. Raw output will also increase by 3.7%. By contrast, apparent density and weight fraction of losses decreases, which has a positive impact on pollen efficiency of use and distribution in bulk yogurt. Moreover, the weight fraction of losses decreases by fourfold (4.6% vs. 1%. It was experimentally determined that pollen can deteriorate microbiological characteristics of yogurt. It was proved that treatment of crushed bee pollen pellet sample with ultraviolet allows improving yogurt microbiological safety indicators. Namely, to reduce the presence of coli-forms to 0, mould –to 10 CFU/cm³. Conclusions. The proposed bee pollen pellet treatment method will improve the technological and microbiological characteristics of pollen powder. This provides for yoghurt production biotechnology using bee farming products.

  5. Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents.

    Science.gov (United States)

    Ma, Junying; Huang, Hongbo; Xie, Yunchang; Liu, Zhiyong; Zhao, Jin; Zhang, Chunyan; Jia, Yanxi; Zhang, Yun; Zhang, Hua; Zhang, Tianyu; Ju, Jianhua

    2017-08-30

    Tuberculosis remains one of the world's deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1-6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6-8) from the respective mutants. Most impressively, ilamycins E 1 /E 2 , which are produced in high titers by a genetically engineered mutant strain, show very potent anti-tuberculosis activity with an minimum inhibitory concentration value ≈9.8 nM to Mycobacterium tuberculosis H37Rv constituting extremely potent and exciting anti-tuberculosis drug leads.Tuberculosis (TB) remains one of the world's deadliest communicable diseases, novel anti-TB agents are urgently needed due to severe drug resistance and the co-epidemic of TB/HIV. Here, the authors show that anti-mycobacterial ilamycin congeners bearing unusual structural units possess extremely potent anti-tuberculosis activities.

  6. Penicillin production in industrial strain Penicillium chrysogenum P2niaD18 is not dependent on the copy number of biosynthesis genes.

    Science.gov (United States)

    Ziemons, Sandra; Koutsantas, Katerina; Becker, Kordula; Dahlmann, Tim; Kück, Ulrich

    2017-02-16

    Multi-copy gene integration into microbial genomes is a conventional tool for obtaining improved gene expression. For Penicillium chrysogenum, the fungal producer of the beta-lactam antibiotic penicillin, many production strains carry multiple copies of the penicillin biosynthesis gene cluster. This discovery led to the generally accepted view that high penicillin titers are the result of multiple copies of penicillin genes. Here we investigated strain P2niaD18, a production line that carries only two copies of the penicillin gene cluster. We performed pulsed-field gel electrophoresis (PFGE), quantitative qRT-PCR, and penicillin bioassays to investigate production, deletion and overexpression strains generated in the P. chrysogenum P2niaD18 background, in order to determine the copy number of the penicillin biosynthesis gene cluster, and study the expression of one penicillin biosynthesis gene, and the penicillin titer. Analysis of production and recombinant strain showed that the enhanced penicillin titer did not depend on the copy number of the penicillin gene cluster. Our assumption was strengthened by results with a penicillin null strain lacking pcbC encoding isopenicillin N synthase. Reintroduction of one or two copies of the cluster into the pcbC deletion strain restored transcriptional high expression of the pcbC gene, but recombinant strains showed no significantly different penicillin titer compared to parental strains. Here we present a molecular genetic analysis of production and recombinant strains in the P2niaD18 background carrying different copy numbers of the penicillin biosynthesis gene cluster. Our analysis shows that the enhanced penicillin titer does not strictly depend on the copy number of the cluster. Based on these overall findings, we hypothesize that instead, complex regulatory mechanisms are prominently implicated in increased penicillin biosynthesis in production strains.

  7. Pep2Path: automated mass spectrometry-guided genome mining of peptidic natural products.

    Directory of Open Access Journals (Sweden)

    Marnix H Medema

    2014-09-01

    Full Text Available Nonribosomally and ribosomally synthesized bioactive peptides constitute a source of molecules of great biomedical importance, including antibiotics such as penicillin, immunosuppressants such as cyclosporine, and cytostatics such as bleomycin. Recently, an innovative mass-spectrometry-based strategy, peptidogenomics, has been pioneered to effectively mine microbial strains for novel peptidic metabolites. Even though mass-spectrometric peptide detection can be performed quite fast, true high-throughput natural product discovery approaches have still been limited by the inability to rapidly match the identified tandem mass spectra to the gene clusters responsible for the biosynthesis of the corresponding compounds. With Pep2Path, we introduce a software package to fully automate the peptidogenomics approach through the rapid Bayesian probabilistic matching of mass spectra to their corresponding biosynthetic gene clusters. Detailed benchmarking of the method shows that the approach is powerful enough to correctly identify gene clusters even in data sets that consist of hundreds of genomes, which also makes it possible to match compounds from unsequenced organisms to closely related biosynthetic gene clusters in other genomes. Applying Pep2Path to a data set of compounds without known biosynthesis routes, we were able to identify candidate gene clusters for the biosynthesis of five important compounds. Notably, one of these clusters was detected in a genome from a different subphylum of Proteobacteria than that in which the molecule had first been identified. All in all, our approach paves the way towards high-throughput discovery of novel peptidic natural products. Pep2Path is freely available from http://pep2path.sourceforge.net/, implemented in Python, licensed under the GNU General Public License v3 and supported on MS Windows, Linux and Mac OS X.

  8. Natural product synthesis at the interface of chemistry and biology

    Science.gov (United States)

    2014-01-01

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880

  9. Strategies for engineering plant natural products: the iridoid-derived monoterpene indole alkaloids of Catharanthus roseus.

    Science.gov (United States)

    O'Connor, Sarah E

    2012-01-01

    The manipulation of pathways to make unnatural variants of natural compounds, a process often termed combinatorial biosynthesis, has been robustly successful in prokaryotic systems. The development of approaches to generate new-to-nature compounds from plant-based pathways is, in comparison, much less advanced. Success will depend on the specific chemistry of the pathway, as well as on the suitability of the plant system for transformation and genetic manipulation. As plant pathways are elucidated, and can be heterologously expressed in hosts that are more amenable to genetic manipulation, biosynthetic production of new-to-nature compounds from plant pathways will become more widespread. In this chapter, some of the key strategies that have been developed for metabolic engineering of plant pathways, namely directed biosynthesis, mutasynthesis, and pathway incorporation of engineered enzymes are highlighted. The iridoid-derived monoterpene indole alkaloids from C. roseus, which are the focus of this chapter, provide an excellent system for developing these strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Applications of natural products in the control of mosquito ...

    African Journals Online (AJOL)

    Applications of natural products in the control of mosquito-transmitted ... African Journal of Biotechnology ... Ultimately, a paradigm shift in research that evaluates natural products in a comparative manner will help to produce new materials for ...

  11. Chocolate: A Marvelous Natural Product of Chemistry

    Science.gov (United States)

    Tannenbaum, Ginger

    2004-08-01

    Chocolate is a natural product as ubiquitous as television. Of course, it is eaten, but it is also found in air fresheners, marking pens, flavoring in a multitude of products including soda pop, and as an aroma in "chocolate-dyed" T-shirts. However, most of us are completely unaware of the complex chemical reactions that take place to produce chocolate and the necessary technology that has evolved to produce chocolate and all its byproducts. Processing results in a mixture of many components, an interesting contrast to most of the simple, one-step reactions introduced at the high school level. This article is a survey of chocolate from tree to table. After a brief introduction to the history of chocolate and how and where it is grown, the manufacturing process is examined, and the chemistry is explored. A bit of the jargon used in the industry is mentioned. Cocoa butter is a significant ingredient in chocolate, and an investigation of it introduces triglycerides, fatty acids, polymorphic behavior, and molecular packing of the fats in chocolate and how they affect the tempering process. There is a brief discussion of chocolate's non-Newtonian behavior and the resulting challenges presented in the manufacturing process. See Featured Molecules Featured on the Cover

  12. Cordyceps fungi: natural products, pharmacological functions and developmental products.

    Science.gov (United States)

    Zhou, Xuanwei; Gong, Zhenghua; Su, Ying; Lin, Juan; Tang, Kexuan

    2009-03-01

    Parasitic Cordyceps fungi, such as Cordyceps sinensis, is a parasitic complex of fungus and caterpillar, which has been used for medicinal purposes for centuries particularly in China, Japan and other Asian countries. This article gives a general idea of the latest developments in C. sinensis research, with regard to the active chemical components, the pharmacological effects and the research and development of products in recent years. The common names for preparations include DongChongXiaCao in Chinese, winter worm summer grass in English. It has many bioactive components, such as 3'-deoxyadenosine, cordycepic acid and Cordyceps polysaccharides. It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. It also can be used to treat conditions such as night sweating, hyposexuality, hyperglycaemia, hyperlipidaemia, asthenia after severe illness, respiratory disease, renal dysfunction, renal failure, arrhythmias and other heart disease and liver disease. Because of its rarity and outstanding curative effects, several mycelia strains have been isolated from natural Cordyceps and manufactured by fermentation technology, and are commonly sold as health food products. In addition, some substitutes such as C. militaris and adulterants also have been used; therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy. Recent research advances in the study of Cordyceps, including Cordyceps mushrooms, chemical components, pharmacological functions and developmental products, has been reviewed and discussed. Developing trends in the field have also been appraised.

  13. Enzymatic Reductive Dehalogenation Controls the Biosynthesis of Marine Bacterial Pyrroles.

    Science.gov (United States)

    El Gamal, Abrahim; Agarwal, Vinayak; Rahman, Imran; Moore, Bradley S

    2016-10-12

    Enzymes capable of performing dehalogenating reactions have attracted tremendous contemporary attention due to their potential application in the bioremediation of anthropogenic polyhalogenated persistent organic pollutants. Nature, in particular the marine environment, is also a prolific source of polyhalogenated organic natural products. The study of the biosynthesis of these natural products has furnished a diverse array of halogenation biocatalysts, but thus far no examples of dehalogenating enzymes have been reported from a secondary metabolic pathway. Here we show that the penultimate step in the biosynthesis of the highly brominated marine bacterial product pentabromopseudilin is catalyzed by an unusual debrominase Bmp8 that utilizes a redox thiol mechanism to remove the C-2 bromine atom of 2,3,4,5-tetrabromopyrrole to facilitate oxidative coupling to 2,4-dibromophenol. To the best of our knowledge, Bmp8 is first example of a dehalogenating enzyme from the established genetic and biochemical context of a natural product biosynthetic pathway.

  14. In vitro biosynthesis of unnatural enterocin and wailupemycin polyketides.

    Science.gov (United States)

    Kalaitzis, John A; Cheng, Qian; Thomas, Paul M; Kelleher, Neil L; Moore, Bradley S

    2009-03-27

    Nature has evolved finely tuned strategies to synthesize rare and complex natural products such as the enterocin family of polyketides from the marine bacterium Streptomyces maritimus. Herein we report the directed ex vivo multienzyme syntheses of 24 unnatural 5-deoxyenterocin and wailupemycin F and G analogues, 18 of which are new. We have generated molecular diversity by priming the enterocin biosynthesis enzymes with unnatural substrates and have illustrated further the uniqueness of this type II polyketide synthase by way of exploiting its unusual starter unit biosynthesis pathways.

  15. Antifouling Activity of Marine Natural Products

    KAUST Repository

    Qian, Pei-Yuan

    2012-01-01

    With the global ban of application of organotin-based marine coatings by International Maritime Organization in 2008, there is a practical and urgent need of identifying environmentally friendly low-toxic and nontoxic antifouling compounds for marine industries. Marine natural products have been considered as one of the most promising sources of antifouling compounds in recent years. In antifouling compound screening processes, bioassay systems often play most critical/vital roles in screening efforts. To meet various needs, a variety of bioassay systems have been developed and/or adopted in both research and commercial laboratories. In this chapter, we provide a brief outline of common bioassay procedures for both antimicrofouling and antimacrofouling assays, which can serve as a general guideline for setting up bioassay systems in laboratories engaged in antifouling compound screening. Some bioassay procedures currently practiced in various laboratories are not included in this book chapter for various reasons. Individual laboratories should modify bioassay protocols based on their research interests or needs. Nevertheless, we highly recommend the research laboratories to adapt high-throughput assays as much as possible for preliminary screening assays, followed by more complex bioassay processes using multiple target species. We argue strongly for studies in mode-of-action of antifouling compounds against settling propagules, which shall lead to discovery of molecular biomarkers (genes, proteins, receptors, or receptor system) and will allow us to design more targeted bioassay systems.

  16. Biosynthesis of platelet activating factor (PAF) via alternate pathways: subcellular distribution of products in HL-60 cells

    International Nuclear Information System (INIS)

    Record, M.; Snyder, F.

    1986-01-01

    Final steps in the biosynthesis of PAF can be catalyzed by two different routes: CDP-choline:1-alkyl-2-acetyl-Gro cholinephosphotransferase [dithiothrietol (DTT)-insensitive] or acetyl-CoA:1-alkyl-2-lyso-GroPCho acetyltransferase. The authors have investigated the conversion of tritium-labeled 1-alkyl-2-acetyl-Gro and 1-alkyl-2-lyso-GroPCho (lyso-PAF) to PAF and other lipid products in HL-60 cells and in subcellular organelles isolated by centrifugation in a Percoll gradient. When cells are incubated with the labeled precursors (2 μM) the total amount of labeled PAF and 1-alkyl-2-acyl-GroPCho formed was similar from both precursors (60 pmol from 1-alkyl-2-acetyl-Gro and 50 pmol from lyso-PAF). However, PAF formed from 1-alkyl-2-acetyl-Gro represented 70% of the total products, whereas with lyso-PAF the major labeled product was 1-alkyl-2-acyl-GroPCho. Formation of PAF from 1-[ 3 H]alkyl-2-acetyl-Gro was linear to at least 30 min at 20 0 C. After a 15-min incubation of this neutral lipid with HL-60 cells, the labeled PAF produced was located exclusively in the plasma membrane fraction as opposed to the label in the 1-alkyl-2-acyl-GroPCho, which was found only in the endoplasmic reticulum; none of the labeled PAF product was released to the media. The authors results suggest PAF might be synthesized by the DTT-insensitive cholinephosphotransferase at the site of the plasma membrane in HL-60 cells

  17. Separation process design for isolation and purification of natural products

    DEFF Research Database (Denmark)

    Malwade, Chandrakant R.

    Natural products are defined as secondary metabolites produced by plants and form a vast pool of compounds with unlimited chemical and functional diversity. Many of these secondary metabolites are high value added chemicals that are frequently used as ingredients in food, cosmetics, pharmaceuticals...... and other consumer products. Therefore, process technology towards industrial scale production of such high value chemicals from plants has significant value. Natural products can be obtained in pure form via synthetic or semi-synthetic route, but due to their complicated nature these methods have not been...... developed to the extent of industrial production for majority of natural products. Thus, isolation and purification of such natural products from plants is the most viable way to obtain natural products in pure form. This PhD project is mainly concerned with the design of separation process to isolate...

  18. Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products.

    Science.gov (United States)

    Prescher, Horst; Koch, Guido; Schuhmann, Tim; Ertl, Peter; Bussenault, Alex; Glick, Meir; Dix, Ina; Petersen, Frank; Lizos, Dimitrios E

    2017-02-01

    A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD). Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Engineered fungal polyketide biosynthesis in Pichia pastoris: a potential excellent host for polyketide production.

    Science.gov (United States)

    Gao, Limei; Cai, Menghao; Shen, Wei; Xiao, Siwei; Zhou, Xiangshan; Zhang, Yuanxing

    2013-09-08

    Polyketides are one of the most important classes of secondary metabolites and usually make good drugs. Currently, heterologous production of fungal polyketides for developing a high potential industrial application system with high production capacity and pharmaceutical feasibility was still at its infancy. Pichia pastoris is a highly successful system for the high production of a variety of heterologous proteins. In this work, we aim to develop a P. pastoris based in vivo fungal polyketide production system for first time and evaluate its feasibility for future industrial application. A recombinant P. pastoris GS115-NpgA-ATX with Aspergillus nidulans phosphopantetheinyl transferase (PPtase) gene npgA and Aspergillus terrus 6-methylsalicylic acid (6-MSA) synthase (6-MSAS) gene atX was constructed. A specific compound was isolated and identified as 6-MSA by HPLC, LC-MS and NMR. Transcription of both genes were detected. In 5-L bioreactor, the GS115-NpgA-ATX grew well and produced 6-MSA quickly until reached a high value of 2.2 g/L by methanol induction for 20 hours. Thereafter, the cells turned to death ascribing to high concentration of antimicrobial 6-MSA. The distribution of 6-MSA changed that during early and late induction phase it existed more in supernatant while during intermediate stage it mainly located intracellular. Different from 6-MSA production strain, recombinant M. purpureus pksCT expression strains for citrinin intermediate production, no matter PksCT located in cytoplasm or in peroxisomes, did not produce any specific compound. However, both npgA and pksCT transcripted effectively in cells and western blot analysis proved the expression of PPtase. Then the PPTase was expressed and purified, marked by fluorescent probes, and reacted with purified ACP domain and its mutant ACPm of PksCT. Fluoresence was only observed in ACP but not ACPm, indicating that the PPTase worked well with ACP to make it bioactive holo-ACP. Thus, some other factors may

  20. Effect of Metals, Metalloids and Metallic Nanoparticles on Microalgae Growth and Industrial Product Biosynthesis: A Review

    Science.gov (United States)

    Miazek, Krystian; Iwanek, Waldemar; Remacle, Claire; Richel, Aurore; Goffin, Dorothee

    2015-01-01

    Microalgae are a source of numerous compounds that can be used in many branches of industry. Synthesis of such compounds in microalgal cells can be amplified under stress conditions. Exposure to various metals can be one of methods applied to induce cell stress and synthesis of target products in microalgae cultures. In this review, the potential of producing diverse biocompounds (pigments, lipids, exopolymers, peptides, phytohormones, arsenoorganics, nanoparticles) from microalgae cultures upon exposure to various metals, is evaluated. Additionally, different methods to alter microalgae response towards metals and metal stress are described. Finally, possibilities to sustain high growth rates and productivity of microalgal cultures in the presence of metals are discussed. PMID:26473834

  1. Effect of Metals, Metalloids and Metallic Nanoparticles on Microalgae Growth and Industrial Product Biosynthesis: A Review

    Directory of Open Access Journals (Sweden)

    Krystian Miazek

    2015-10-01

    Full Text Available Microalgae are a source of numerous compounds that can be used in many branches of industry. Synthesis of such compounds in microalgal cells can be amplified under stress conditions. Exposure to various metals can be one of methods applied to induce cell stress and synthesis of target products in microalgae cultures. In this review, the potential of producing diverse biocompounds (pigments, lipids, exopolymers, peptides, phytohormones, arsenoorganics, nanoparticles from microalgae cultures upon exposure to various metals, is evaluated. Additionally, different methods to alter microalgae response towards metals and metal stress are described. Finally, possibilities to sustain high growth rates and productivity of microalgal cultures in the presence of metals are discussed.

  2. Effect of Metals, Metalloids and Metallic Nanoparticles on Microalgae Growth and Industrial Product Biosynthesis: A Review.

    Science.gov (United States)

    Miazek, Krystian; Iwanek, Waldemar; Remacle, Claire; Richel, Aurore; Goffin, Dorothee

    2015-10-09

    Microalgae are a source of numerous compounds that can be used in many branches of industry. Synthesis of such compounds in microalgal cells can be amplified under stress conditions. Exposure to various metals can be one of methods applied to induce cell stress and synthesis of target products in microalgae cultures. In this review, the potential of producing diverse biocompounds (pigments, lipids, exopolymers, peptides, phytohormones, arsenoorganics, nanoparticles) from microalgae cultures upon exposure to various metals, is evaluated. Additionally, different methods to alter microalgae response towards metals and metal stress are described. Finally, possibilities to sustain high growth rates and productivity of microalgal cultures in the presence of metals are discussed.

  3. Pharmaceuticals from natural products: current trends

    Directory of Open Access Journals (Sweden)

    PETER R. SEIDL

    2002-03-01

    Full Text Available The use of products extracted from plants for medicinal purposes can be traced to the beginnings of civilization and up until the end of the nineteenth century natural products were the principal source of medicines. Since then their relative importance has oscillated according to the strategies of large pharmaceutical companies. Now that these strategies are changing, there are new opportunities for countries like Brazil, in which a large proportion of the world's biodiversity is located. There are, however, new circumstances that must be taken into consideration: material must be collected by groups which are formally authorized to do so and under the conditions of the Convention of Biological Diversity, the discovery process is being successively outsourced to smaller specialized firms and there is a growing integration with producers of cosmetics and phytomedicines.O uso de produtos extraídos de plantas para fins medicinais pode ser tracejado aos inícios da civilização e até o fim do século XIX, os produtos naturais constituíram a principal fonte de medicamentos. Desde então, a importância relativa dos produtos naturais tem oscilado de acordo com as estratégias de grandes companhias farmacêuticas. Agora que estas estratégias vêm mudando, há novas oportunidades para países como o Brasil, no qual está localizada uma vasta proporção da biodiversidade mundial. Há, entretanto, novas circunstâncias que devem ser levadas em consideração: o material deve ser coletado por grupos que estão formalmente autorizados para tal, com a coleta sendo feita sob as condições da Convenção de Diversidade Biológica, o processo de descoberta está sendo sucessivamente terceirizado no sentido de firmas especializadas menores e há uma integração crescente como produtores de cosméticos e fitomedicamentos.

  4. The rare fluorinated natural products and biotechnological prospects for fluorine enzymology.

    Science.gov (United States)

    Chan, K K Jason; O'Hagan, David

    2012-01-01

    Nature has hardly evolved a biochemistry of fluorine although there is a low-level occurrence of fluoroacetate found in selected tropical and subtropical plants. This compound, which is generally produced in low concentrations, has been identified in the plants due to its high toxicity, although to date the biosynthesis of fluoroacetate in plants remains unknown. After that, fluorinated entities in nature are extremely rare, and despite increasingly sophisticated screening and analytical methods applied to natural product extraction, it has been 25 years since the last bona fide fluorinated natural product was identified from an organism. This was the reported isolation of the antibiotic 4-fluorothreonine and the toxin fluoroacetate in 1986 from Streptomyces cattleya. This bacterium has proven amenable to biochemical investigation, the fluorination enzyme (fluorinase) has been isolated and characterized, and the biosynthetic pathway to these bacterial metabolites has been elucidated. Also the fluorinase gene has been cloned into a host bacterium (Salinispora tropica), and this has enabled the de novo production of a bioactive fluorinated metabolite from fluoride ion, by genetic engineering. Biotechnological manipulation of the fluorinase offers the prospects for the assembly of novel fluorinated metabolites by fermentation technology. This is particularly attractive, given the backdrop that about 15-20% of pharmaceuticals licensed each year (new chemical entities) contain a fluorine atom. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.

    Science.gov (United States)

    Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R

    2018-06-13

    The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.

  6. Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

    KAUST Repository

    Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S.; Qian, Pei-Yuan

    2015-01-01

    validating this direct cloning plug-and-playa approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation

  7. Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases

    Science.gov (United States)

    Itoh, Takayuki; Tokunaga, Kinya; Matsuda, Yudai; Fujii, Isao; Abe, Ikuro; Ebizuka, Yutaka; Kushiro, Tetsuo

    2010-10-01

    Meroterpenoids are hybrid natural products of both terpenoid and polyketide origin. We identified a biosynthetic gene cluster that is responsible for the production of the meroterpenoid pyripyropene in the fungus Aspergillus fumigatus through reconstituted biosynthesis of up to five steps in a heterologous fungal expression system. The cluster revealed a previously unknown terpene cyclase with an unusual sequence and protein primary structure. The wide occurrence of this sequence in other meroterpenoid and indole-diterpene biosynthetic gene clusters indicates the involvement of these enzymes in the biosynthesis of various terpenoid-bearing metabolites produced by fungi and bacteria. In addition, a novel polyketide synthase that incorporated nicotinyl-CoA as the starter unit and a prenyltransferase, similar to that in ubiquinone biosynthesis, was found to be involved in the pyripyropene biosynthesis. The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities.

  8. Zincophorin – biosynthesis in Streptomyces griseus and antibiotic properties

    Directory of Open Access Journals (Sweden)

    Walther, Elisabeth

    2016-11-01

    Full Text Available Zincophorin is a polyketide antibiotic that possesses potent activity against Gram-positive bacteria, including human pathogens. While a number of total syntheses of this highly functionalized natural product were reported since its initial discovery, the genetic basis for the biosynthesis of zincophorin has remained unclear. In this study, the co-linearity inherent to polyketide pathways was used to identify the zincophorin biosynthesis gene cluster in the genome of the natural producer HKI 0741. Interestingly, the same locus is fully conserved in the streptomycin-producing actinomycete IFO 13350, suggesting that the latter bacterium is also capable of zincophorin biosynthesis. Biological profiling of zincophorin revealed a dose-dependent inhibition of the Gram-positive bacterium . The antibacterial effect, however, is accompanied by cytotoxicity. Antibiotic and cytotoxic activities were completely abolished upon esterification of the carboxylic acid group in zincophorin.

  9. Tropane and nicotine alkaloid biosynthesis-novel approaches towards biotechnological production of plant-derived pharmaceuticals.

    Science.gov (United States)

    Oksman-Caldentey, Kirsi-Marja

    2007-08-01

    Many plants belonging to the Solanaceae family have been used as a source of pharmaceuticals for centuries because of their active principles, tropane and nicotine alkaloids. Tropane alkaloids, atropine, hyoscyamine and scopolamine, are among the oldest drugs in medicine. On the other hand nicotine, the addictive agent in tobacco, has only recently gained attention as a backbone for novel potential alkaloids to be used for certain neurological diseases. The biotechnological production of alkaloids utilizing plant cells as hosts would be an attractive option. However, to date very little success in this field has been gained because of the lack of understanding how these compounds are synthesized in a plant cell. Metabolic engineering attempts have already shown that when the rate-limiting steps of the biosynthetic pathway are completely known and the respective genes cloned, the exact regulation towards desired medicinal products will be possible in the near future. The new functional genomics tools, which combine transcriptome and metabolome data, will create a platform to better understand a whole system and to engineer the complex plant biosynthetic pathways. With the help of this technology, it is not only possible to produce known plant metabolites more effectively but also to make arrays of new compounds in plants and cell cultures.

  10. Bioactivities, biosynthesis and biotechnological production of phenolic acids in Salvia miltiorrhiza.

    Science.gov (United States)

    Shi, Min; Huang, Fenfen; Deng, Changping; Wang, Yao; Kai, Guoyin

    2018-05-10

    Salvia miltiorrhiza (Danshen in Chinese), is a well-known traditional Chinese medicinal plant, which is used as not only human medicine but also health-promotion food. Danshen has been extensively used for the treatment of various cardiovascular and cerebrovascular diseases. As a major group of bioactive constituents from S. miltiorrhiza, water-soluble phenolic acids such as salvianolic acid B possessed good bioactivities including antioxidant, anti-inflammatory, anti-cancer and other health-promoting activities. It is of significance to improve the production of phenolic acids by modern biotechnology approaches to meet the increasing market demand. Significant progresses have been made in understanding the biosynthetic pathway and regulation mechanism of phenolic acids in S.miltiorrhiza, which will facilitate the process of targeted metabolic engineering or synthetic biology. Furthermore, multiple biotechnology methods such as in vitro culture, elicitation, hairy roots, endophytic fungi and bioreactors have been also used to obtain pharmaceutically active phenolic acids from S. miltiorrhiza. In this review, recent advances in bioactivities, biosynthetic pathway and biotechnological production of phenolic acid ingredients were summarized and future prospective was also discussed.

  11. Deposition of naturally occurring radioactivity in oil and gas production

    International Nuclear Information System (INIS)

    Lysebo, I.; Strand, T.

    1997-01-01

    This booklet contains general information about naturally occurring radioactive materials, NORM, in production of oil and natural gas, occupational doses, radiation protection procedures and measures, and classification methods of contaminated equipment. 6 refs., 1 fig., 1 tab

  12. Effect of Lignocellulose Related Compounds on Microalgae Growth and Product Biosynthesis: A Review

    Directory of Open Access Journals (Sweden)

    Krystian Miazek

    2014-07-01

    Full Text Available Microalgae contain valuable compounds that can be harnessed for industrial applications. Lignocellulose biomass is a plant material containing in abundance organic substances such as carbohydrates, phenolics, organic acids and other secondary compounds. As growth of microalgae on organic substances was confirmed during heterotrophic and mixotrophic cultivation, lignocellulose derived compounds can become a feedstock to cultivate microalgae and produce target compounds. In this review, different treatment methods to hydrolyse lignocellulose into organic substrates are presented first. Secondly, the effect of lignocellulosic hydrolysates, organic substances typically present in lignocellulosic hydrolysates, as well as minor co-products, on growth and accumulation of target compounds in microalgae cultures is described. Finally, the possibilities of using lignocellulose hydrolysates as a common feedstock for microalgae cultures are evaluated.

  13. Organosilicon Reagents in Natural Product Synthesis

    Indian Academy of Sciences (India)

    Organosilicon compounds do not occur free in nature, and are ... work was carried out by Kipping, copsidered today as the father of classical organosilicon chemistry. The ..... v V V V V v. 55 ..... Sweet potato leaf folder moth pheromone.

  14. Linking neuroethology to the chemical biology of natural products

    DEFF Research Database (Denmark)

    Olivera, Baldomero M.; Raghuraman, Shrinivasan; Schmidt, Eric W.

    2017-01-01

    From a biological perspective, a natural product can be defined as a compound evolved by an organism for chemical interactions with another organism including prey, predator, competitor, pathogen, symbiont or host. Natural products hold tremendous potential as drug leads and have been extensively...... a better understanding of the evolution, biology and biochemistry of natural products will facilitate both neuroscience and the potential for drug leads. The larger goal is to establish a new sub-discipline in the broader field of neuroethology that we refer to as “Chemical Neuroethology”, linking...... the substantial work carried out by chemists on natural products with accelerating advances in neuroethology....

  15. Covalent attachment of the plant natural product naringenin to small glass and ceramic beads

    Directory of Open Access Journals (Sweden)

    Grotewold Erich

    2005-10-01

    Full Text Available Abstract Background Natural products have numerous medicinal applications and play important roles in the biology of the organisms that accumulate them. Few methods are currently available for identifying proteins that bind to small molecules, therefore the discovery of cellular targets for natural products with pharmacological activity continues to pose a significant challenge in drug validation. Similarly, the identification of enzymes that participate in the biosynthesis or modification of natural products remains a formidable bottleneck for metabolic engineering. Flavonoids are one large group of natural products with a diverse number of functions in plants and in human health. The coupling of flavonoids to small ceramic and glass beads provides a first step in the development of high-throughput, solid-support base approaches to screen complex libraries to identify proteins that bind natural products. Results The utilization of small glass and ceramic beads as solid supports for the coupling of small molecules was explored. Initial characterization of the beads indicated uniform and high capacity loading of amino groups. Once the beads were deemed adequate for the linking of small molecules by the coupling of NHS-fluorescein followed by microscopy, chemical hydrolysis and fluorometry, the flavonoid naringenin was modified with 1,4-dibromobutane, followed by the attachment of aminopropyltriethoxysilane. After NMR structural confirmation, the resulting 7-(4-(3-(triethoxysilylpropylaminobutoxy naringenin was attached to the ceramic beads. Conclusion Our results demonstrate that ceramic and glass beads provide convenient solid supports for the efficient and facile coupling of small molecules. We succeeded in generating naringenin-coupled ceramic and glass beads. We also developed a convenient series of steps that can be applied for the solid-support coupling of other related flavonoids. The availability of solid-support coupled naringenin opens

  16. Bacterial Glycosyltransferases: Challenges and opportunities of a highly diverse enzyme class toward tailoring natural products

    Directory of Open Access Journals (Sweden)

    Jochen eSchmid

    2016-02-01

    Full Text Available The enzyme subclass of glycosyltransferases (EC 2.4 currently comprises 97 families as specified by CAZy classification. One of their important roles is in the biosynthesis of disaccharides, oligosaccharides and polysaccharides by catalyzing the transfer of sugar moieties from activated donor molecules to other sugar molecules. In addition glycosyltransferases also catalyze the transfer of sugar moieties onto aglycons, which is of great relevance for the synthesis of many high value natural products. Bacterial glycosyltransferases show a higher sequence similarity in comparison to mammalian ones. Even when most glycosyltransferases are poorly explored, state of the art technologies, such as protein engineering, domain swapping or computational analysis strongly enhance our understanding and utilization of these very promising classes of proteins. This perspective article will focus on bacterial glycosyltransferases, especially on classification, screening and engineering strategies to alter substrate specificity. The future development in these fields as well as obstacles and challenges will be highlighted and discussed.

  17. Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids.

    Science.gov (United States)

    Schimming, Olivia; Challinor, Victoria L; Tobias, Nicholas J; Adihou, Hélène; Grün, Peter; Pöschel, Laura; Richter, Christian; Schwalbe, Harald; Bode, Helge B

    2015-10-19

    Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non-ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram-negative and Gram-positive bacteria indicates an important biological function in bacteria. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Natural Products and Dietary Prevention of Cancer

    Science.gov (United States)

    The concept of cancer prevention was first introduced in studies using the natural form of vitamin A in the prevention of epithelial cancers. Ever since, research on cancer prevention has grown and become a rather specialized field study. Cancer is a multistage process, and takes several years for...

  19. Data feature World natural Uranium production 1992

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    NUKEM estimates that world uranium production fell more than 13% last year, from 40,729 tonnes U [106 million lbs U308] in 1991 to 35,363 tonnes U [92 million lbs U308] in 1992. Production fell in both the Western World and non-Western World. How much of demand was met by production? World uranium production in 1992 amounted to about 65% of reactor consumption. That's assuming that reactor demand of the non-Western World has not changed much from the Uranium Institute's estimate for 1991. Civilian stockpiles are being drawn down on a massive scale while the world waits to see what will become of the military stockpiles that could soon enter the global supply picture

  20. Biosynthesis of antimycins with a reconstituted 3-formamidosalicylate pharmacophore in Escherichia coli.

    Science.gov (United States)

    Liu, Joyce; Zhu, Xuejun; Seipke, Ryan F; Zhang, Wenjun

    2015-05-15

    Antimycins are a family of natural products generated from a hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line. Although they possess an array of useful biological activities, their structural complexity makes chemical synthesis challenging, and their biosynthesis has thus far been dependent on slow-growing source organisms. Here, we reconstituted the biosynthesis of antimycins in Escherichia coli, a versatile host that is robust and easy to manipulate genetically. Along with Streptomyces genetic studies, the heterologous expression of different combinations of ant genes enabled us to systematically confirm the functions of the modification enzymes, AntHIJKL and AntO, in the biosynthesis of the 3-formamidosalicylate pharmacophore of antimycins. Our E. coli-based antimycin production system can not only be used to engineer the increased production of these bioactive compounds, but it also paves the way for the facile generation of novel and diverse antimycin analogues through combinatorial biosynthesis.

  1. Metagenomic Analysis of the Sponge Discodermia Reveals the Production of the Cyanobacterial Natural Product Kasumigamide by 'Entotheonella'.

    Science.gov (United States)

    Nakashima, Yu; Egami, Yoko; Kimura, Miki; Wakimoto, Toshiyuki; Abe, Ikuro

    2016-01-01

    Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synthase-nonribosomal peptide synthetase gene (kas). Bioinformatic analysis of the gene product suggested its involvement in the biosynthesis of kasumigamide, a tetrapeptide originally isolated from freshwater free-living cyanobacterium Microcystis aeruginosa NIES-87. Subsequent investigation of the sponge metabolic profile revealed the presence of kasumigamide in the sponge extract. The kasumigamide producing bacterium was identified as an 'Entotheonella' sp. Moreover, an in silico analysis of kas gene homologs uncovered the presence of kas family genes in two additional bacteria from different phyla. The production of kasumigamide by distantly related multiple bacterial strains implicates horizontal gene transfer and raises the potential for a wider distribution across other bacterial groups.

  2. Taxonomy, Physiology, and Natural Products of Actinobacteria

    OpenAIRE

    Barka, Essaid Ait; Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder; van Wezel, Gilles P.

    2015-01-01

    Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal c...

  3. T R Seshadri's Contributions to the Chemistry of Natural Products

    Indian Academy of Sciences (India)

    Sri Sathya Sai Institute of. Higher Learning. Generations of students would vouch for the fact that he has the uncanny ability to present the chemistry of natural products logically and with feeling. Keywords. Flavonoids, lichen metabolite, methylation, Elbs-Seshadri oxi- dation, structure elucidation, natural products synthesis.

  4. Remote methods of indicating oil products in natural waters

    Energy Technology Data Exchange (ETDEWEB)

    Shlyakhova, L A

    1981-01-01

    A survey is made of domestic and foreign publications covering remote methods of monitoring film petroleum products and oil in natural waters. The given methods are realized in practice with the use of different sections of the electromagnetic spectrum. Remote quality control of the natural waters at the modern level may be an indicator of water pollution with film petroleum products.

  5. Phytotherapy natural products: Promotional mix features

    Directory of Open Access Journals (Sweden)

    Dugalić Sretenka L.

    2002-01-01

    Full Text Available Development of products takes into account organized and controlled planning of changes of inner self and toward the environment. That means the creation of an active force, which should bring changes in other words, it should change the person who participates in the process of creation or in the consumption of the product. It tried to induce customers to purchase through methodologies and promotion strategies which stand to our sen'ice by the change in the way of thinking of the medical and pharmaceutical profession and users of helpful means. The input of marketing within the control of the outcomes, leaders techniques and promotion strategies by the production of helpful healthy means has a very big meaning.

  6. Early activation of wheat polyamine biosynthesis during Fusarium head blight implicates putrescine as an inducer of trichothecene mycotoxin production

    Directory of Open Access Journals (Sweden)

    Rusu Anca

    2010-12-01

    Full Text Available Abstract Background The fungal pathogen Fusarium graminearum causes Fusarium Head Blight (FHB disease on wheat which can lead to trichothecene mycotoxin (e.g. deoxynivalenol, DON contamination of grain, harmful to mammalian health. DON is produced at low levels under standard culture conditions when compared to plant infection but specific polyamines (e.g. putrescine and agmatine and amino acids (e.g. arginine and ornithine are potent inducers of DON by F. graminearum in axenic culture. Currently, host factors that promote mycotoxin synthesis during FHB are unknown, but plant derived polyamines could contribute to DON induction in infected heads. However, the temporal and spatial accumulation of polyamines and amino acids in relation to that of DON has not been studied. Results Following inoculation of susceptible wheat heads by F. graminearum, DON accumulation was detected at two days after inoculation. The accumulation of putrescine was detected as early as one day following inoculation while arginine and cadaverine were also produced at three and four days post-inoculation. Transcripts of ornithine decarboxylase (ODC and arginine decarboxylase (ADC, two key biosynthetic enzymes for putrescine biosynthesis, were also strongly induced in heads at two days after inoculation. These results indicated that elicitation of the polyamine biosynthetic pathway is an early response to FHB. Transcripts for genes encoding enzymes acting upstream in the polyamine biosynthetic pathway as well as those of ODC and ADC, and putrescine levels were also induced in the rachis, a flower organ supporting DON production and an important route for pathogen colonisation during FHB. A survey of 24 wheat genotypes with varying responses to FHB showed putrescine induction is a general response to inoculation and no correlation was observed between the accumulation of putrescine and infection or DON accumulation. Conclusions The activation of the polyamine biosynthetic

  7. The Arabidopsis aldehyde oxidase 3 (AA03) gene product catalyzes the final step in abscisic acid biosynthesis in leaves

    NARCIS (Netherlands)

    Seo, M.; Peeters, A.J.M.; Koiwai, H.; Oritani, T.; Marion-Poll, A.; Zeevaart, J.A.D.; Koornneef, M.; Kamiya, Y.; Koshiba, T.

    2000-01-01

    Abscisic acid (ABA) is a plant hormone involved in seed development and germination and in responses to various environmental stresses. The last step of ABA biosynthesis involves oxidation of abscisic aldehyde, and aldehyde oxidase (EC 1.2.3.1) is thought to catalyze this reaction. An aldehyde

  8. Natural products: the new engine for African trade growth

    OpenAIRE

    Bennett, Ben

    2006-01-01

    This report was to further develop the trade component of the Natural Resources Enterprise Programme (NATPRO). The field work was undertaken in Malawi, Zimbabwe, Namibia, the Republic of South Africa and the United Kingdom between 9th January and 25th February 2006. The work concentrated on ten countries in Southern Africa with potential to export significant quantities of natural products. These products are defined by the project as follows: being plant derived, occurring naturally, wild ha...

  9. RNA interference of pheromone biosynthesis-activating neuropeptide receptor suppresses mating behavior by inhibiting sex pheromone production in Plutella xylostella (L.).

    Science.gov (United States)

    Lee, Dae-Weon; Shrestha, Sony; Kim, A Young; Park, Seok Joo; Yang, Chang Yeol; Kim, Yonggyun; Koh, Young Ho

    2011-04-01

    Sex pheromone production is regulated by pheromone biosynthesis-activating neuropeptide (PBAN) in many lepidopteran species. We cloned a PBAN receptor (Plx-PBANr) gene from the female pheromone gland of the diamondback moth, Plutella xylostella (L.). Plx-PBANr encodes 338 amino acids and has conserved structural motifs implicating in promoting G protein coupling and tyrosine-based sorting signaling along with seven transmembrane domains, indicating a typical G protein-coupled receptor. The expression of Plx-PBANr was found only in the pheromone gland of female adults among examined tissues and developmental stages. Heterologous expression in human uterus cervical cancer cells revealed that Plx-PBANr induced significant calcium elevation when challenged with Plx-PBAN. Female P. xylostella injected with double-stranded RNA specific to Plx-PBANr showed suppression of the receptor gene expression and exhibited significant reduction in pheromone biosynthesis, which resulted in loss of male attractiveness. Taken together, the identified PBAN receptor is functional in PBAN signaling via calcium secondary messenger, which leads to activation of pheromone biosynthesis and male attraction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. NATURAL ANTIOXIDANTS IN PRODUCTION “BRUSHWOOD”

    Directory of Open Access Journals (Sweden)

    G. N. Dubtsova

    2015-01-01

    Full Text Available Flour wares use popularity, there is 48% of general volume of pastry wares on their stake. A marketing study on results that actuality of development of new type of flour good is set with the lowered maintenance of fat and enriched by vitamins is undertaken. The use of natural antioxidant of "Guarding is reasonable toco 70" and introduction of 0,2% is recommended for stabilizing of sunflower-seed oil at fry of frying. Joint introduction of powders is studied from the garden-stuffs of brier and unabi on quality of the brushwood fried in sunflower-seed oil with the use of "Guarding toco 70". From wares extracted lipids and estimated on indexes: peroxides, acid and anizid numbers. It is set that an antioxidant and vegetable powders assist the decline of indexes of safety peroxides and asid in two times, and anizid in 1,3 time. Use of antioxidant of "Guarding toco 70", being in 70% from the natural concentrate of mixture of tocopherolss and 30% of soyaoil.

  11. Increasing L-threonine production in Escherichia coli by engineering the glyoxylate shunt and the L-threonine biosynthesis pathway.

    Science.gov (United States)

    Zhao, Hui; Fang, Yu; Wang, Xiaoyuan; Zhao, Lei; Wang, Jianli; Li, Ye

    2018-04-30

    L-threonine is an important amino acid that can be added in food, medicine, or feed. Here, the influence of glyoxylate shunt on an L-threonine producing strain Escherichia coli TWF001 has been studied. The gene iclR was deleted, and the native promoter of the aceBA operon was replaced by the trc promoter in the chromosome of TWF001, the resulting strainTWF004 could produce 0.39 g L-threonine from1 g glucose after 36-h flask cultivation. Further replacing the native promoter of aspC by the trc promoter in the chromosome of TWF004 resulted in the strain TWF006. TWF006 could produce 0.42 g L-threonine from 1 g glucose after 36-h flask cultivation. Three key genes in the biosynthetic pathway of L-threonine, thrA * (a mutated thrA), thrB, and thrC were overexpressed in TWF006, resulting the strain TWF006/pFW01-thrA * BC. TWF006/pFW01-thrA * BC could produce 0.49 g L-threonine from 1 g glucose after 36-h flask cultivation. Next, the genes asd, rhtA, rhtC, or thrE were inserted into the plasmid TWF006/pFW01-thrA * BC, and TWF006 was transformed with these plasmids, resulting the strains TWF006/pFW01-thrA * BC-asd, TWF006/pFW01-thrA * BC-rhtA, TWF006/pFW01-thrA * BC-rhtC, and TWF006/pFW01-thrA * BC-thrE, respectively. These four strains could produce more L-threonine than the control strain, and the highest yield was produced by TWF006/pFW01-thrA * BC-asd; after 36-h flask cultivation, TWF006/pFW01-thrA * BC-asd could produce 15.85 g/l L-threonine, i.e., 0.53 g L-threonine per 1 g glucose, which is a 70% increase relative to the control strain TWF001. The results suggested that the combined engineering of glyoxylate shunt and L-threonine biosynthesis pathway could significantly increase the L-threonine production in E. coli.

  12. Natural products-friends or foes?

    Science.gov (United States)

    Margină, Denisa; Ilie, Mihaela; Grădinaru, Daniela; Androutsopoulos, Vasilis P; Kouretas, Demetrios; Tsatsakis, Aristidis M

    2015-08-05

    A trend in the general population has been observed in recent years regarding the orientation toward preventive measures in health; in this context the increased interest from the users and researchers concerning the active effect of food supplements on the health state and on longevity, is noticeable. All over the world, the consumption of natural foods and of vegetal supplements has increased spectacularly over the last 5-10 years. The decreased prevalence of cardio-vascular diseases associated with Mediterranean diet, as well as the French paradox convinced researchers to scientifically document the beneficial outcomes pointed out by traditional use of plants, and to try to develop supplements that would have the same positive effects as these noticed for diet components. The intense research dedicated to this topic revealed the fact that food supplements are linked to some problematic aspects, such as toxicological side effects when associated with classical synthetic drugs. The food supplement-drug interactions are submitted to complex issues regarding pharmacokinetic interactions leading to changes in absorption, distribution, metabolism and excretion processes with direct impact on effect and toxicological potential. The present review based on recent literature aims at discussing the food-drug interactions with direct impact on efficacy and toxicity of drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. MANUFACTURING NATURAL KILLER CELLS AS MEDICINAL PRODUCTS

    Directory of Open Access Journals (Sweden)

    Christian CHABANNON

    2016-11-01

    Full Text Available Natural Killer (NK cells are Innate Lymphoid Cells (ILC with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of HLA presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, either in vivo or in vitro, in a variety of human diseases, including cancers. NK cell activity can possibly be modulated in vivo through direct or indirect actions exerted by small molecules or monoclonal antibodies. NK cells can also be adoptively transferred following more or less substantial modifications through cell and gene manufacturing, in order to empower them with new or improved functions and ensure their controlled persistence and activity in the recipient. In the present review, we will focus on the technological and regulatory challenges of NK cell manufacturing, and discuss conditions in which these innovative cellular therapies can be brought to the clinic.

  14. Taxonomy, Physiology, and Natural Products of Actinobacteria.

    Science.gov (United States)

    Barka, Essaid Ait; Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Meier-Kolthoff, Jan P; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder; van Wezel, Gilles P

    2016-03-01

    Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Structure-based synthesis from natural products to drug prototypes

    International Nuclear Information System (INIS)

    Hanessian, S.

    2009-01-01

    X-Ray crystallographic data available from complexes of natural and synthetic molecules with the enzyme thrombin has aided to the design and synthesis of truncated and hybrid molecules exhibiting excellent inhibition in vitro. The vital importance of natural products for the well-being of man has been known lor millennia. Their therapeutic benefits to alleviate pain or cure diseases continue to rank natural products among the primary sources of potential drugs. Great advances have been made in the methods of isolation, identification, and structure elucidation of some of the most complex natural products in recent years. The advent of molecular biology and genetic mapping has also aided in our understanding of the intriguing biosynthetic pathways leading to various classes of therapeutically relevant antibiotic, anticancer, and related natural products. Elegant and practical methodology has been developed leading to the total synthesis of virtually every class of medicinally important natural product. In some cases, natural products or their chemically modified congeners have been manufactured by total synthesis on an industrial level which is a testament to the ingenuity of process chemists. In spite of their potent activities HI enzymatic ox receptor-mediated assays, not all natural products are amenable to being developed as marketable drags. In many instances unfavorable pharmacological effects cannot be overcome without drastic structural and functional modifications, which may also result in altered efficacy. Structure modification through truncation, functional group variations, isosteric replacements, and skeletal rigidifications aided by molecular modeling, X ray crystallography of protein targets, or NMR data are valid objectives in the context of small molecule drug discovery starting with bioactive natural products. A large proportion of these pertain to chemotherapeutic agents against cancer

  16. Plant natural products research in tuberculosis drug discovery and ...

    African Journals Online (AJOL)

    Plant natural products research in tuberculosis drug discovery and development: A situation report ... African Journal of Biotechnology ... tuberculosis (XDR-TB), call for the development of new anti-tuberculosis drugs to combat this disease.

  17. Marine organisms: an alternative source of potentially valuable natural products

    Directory of Open Access Journals (Sweden)

    Alphonse Kelecom

    1991-01-01

    Full Text Available This paper recalls the outcoming of marine natural products research and reviews a selection of marirne bioactive metabolites in current use together with promising trends in marine pharmacology.

  18. Does species diversity limit productivity in natural grassland communities?

    NARCIS (Netherlands)

    Grace, James B.; Anderson, T. Michael; Smith, Melinda D.; Seabloom, Eric; Andelman, Sandy J.; Meche, Gayna; Weiher, Evan; Allain, Larry K.; Jutila, Heli; Sankaran, Mahesh; Knops, Johannes; Ritchie, Mark; Willig, Michael R.

    Theoretical analyses and experimental studies of synthesized assemblages indicate that under particular circumstances species diversity can enhance community productivity through niche complementarity. It remains unclear whether this process has important effects in mature natural ecosystems where

  19. Natural products in soil microbe interactions and evolution.

    Science.gov (United States)

    Traxler, Matthew F; Kolter, Roberto

    2015-07-01

    In recent years, bacterial interspecies interactions mediated by small molecule natural products have been found to give rise to a surprising array of phenotypes in soil-dwelling bacteria, especially among Streptomyces and Bacillus species. This review examines these interspecies interactions, and the natural products involved, as they have been presented in literature stemming from four disciplines: soil science, interspecies microbiology, ecology, and evolutionary biology. We also consider how these interactions fit into accepted paradigms of signaling, cueing, and coercion.

  20. Anti-Enterovirus 71 Agents of Natural Products

    Directory of Open Access Journals (Sweden)

    Liyan Wang

    2015-09-01

    Full Text Available This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.

  1. Anti-Enterovirus 71 Agents of Natural Products.

    Science.gov (United States)

    Wang, Liyan; Wang, Junfeng; Wang, Lishu; Ma, Shurong; Liu, Yonghong

    2015-09-09

    This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.

  2. Bioactive activities of natural products against herpesvirus infection.

    Science.gov (United States)

    Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

    2013-10-01

    More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

  3. Biosynthesis of silver nanoparticles by Aspergillus niger , Fusarium ...

    African Journals Online (AJOL)

    ... scanning electron microscope (SEM). Results indicate the synthesis of silver nanoparticles in the reaction mixture. The synthesis of nanoparticles would be suitable for developing a microbial nanotechnology biosynthesis process for mass scale production. Keywords: Silver nanoparticles, biosynthesis, fungi, Aspergillus.

  4. Microbial production of 1-octanol: A naturally excreted biofuel with diesel-like properties

    Directory of Open Access Journals (Sweden)

    M. Kalim Akhtar

    2015-12-01

    Full Text Available The development of sustainable, bio-based technologies to convert solar energy and carbon dioxide into fuels is a grand challenge. A core part of this challenge is to produce a fuel that is compatible with the existing transportation infrastructure. This task is further compounded by the commercial desire to separate the fuel from the biotechnological host. Based on its fuel characteristics, 1-octanol was identified as an attractive metabolic target with diesel-like properties. We therefore engineered a synthetic pathway specifically for the biosynthesis of 1-octanol in Escherichia coli BL21(DE3 by over-expression of three enzymes (thioesterase, carboxylic acid reductase and aldehyde reductase and one maturation factor (phosphopantetheinyl transferase. Induction of this pathway in a shake flask resulted in 4.4 mg 1-octanol L−1 h−1 which exceeded the productivity of previously engineered strains. Furthermore, the majority (73% of the fatty alcohol was localised within the media without the addition of detergent or solvent overlay. The deletion of acrA reduced the production and excretion of 1-octanol by 3-fold relative to the wild-type, suggesting that the AcrAB–TolC complex may be responsible for the majority of product efflux. This study presents 1-octanol as a potential fuel target that can be synthesised and naturally accumulated within the media using engineered microbes. Keywords: 1-Octanol, Fatty alcohol, Diesel, Biofuel, Excretion

  5. Emerging trends in the discovery of natural product antibacterials

    DEFF Research Database (Denmark)

    Bologa, Cristian G; Ursu, Oleg; Oprea, Tudor

    2013-01-01

    This article highlights current trends and advances in exploiting natural sources for the deployment of novel and potent anti-infective countermeasures. The key challenge is to therapeutically target bacterial pathogens that exhibit a variety of puzzling and evolutionarily complex resistance...... mechanisms. Special emphasis is given to the strengths, weaknesses, and opportunities in the natural product antibacterial drug discovery arena, and to emerging applications driven by advances in bioinformatics, chemical biology, and synthetic biology in concert with exploiting bacterial phenotypes....... These efforts have identified a critical mass of natural product antibacterial lead compounds and discovery technologies with high probability of successful implementation against emerging bacterial pathogens....

  6. Natural product mode of action (MOA) studies: a link between natural and synthetic worlds.

    Science.gov (United States)

    La Clair, James J

    2010-07-01

    In our understanding of matter, natural products deliver plots that would stun even the best productions of the legendary filmmaker, Sergio Leone. While every decade heralds a new genre of film (as well as avenues of small-molecule discovery), natural products and their "untamed prehistoric" plots continue to dazzle the fields of biotechnology, drug discovery, fragrances, food additives and agrochemistry. This review provides an abridged synopsis of the modes of natural product action discovered within the last decade and the tools and methods used in their discovery. Their stories are united in a common theme that unveils one of the more vital aspects of chemical biological research:understanding the global activity of Nature's arsenal of secondary metabolites.

  7. Nature-Inspired Design : Strategies for Sustainable Product Development

    NARCIS (Netherlands)

    De Pauw, I.C.

    2015-01-01

    Product designers can apply different strategies, methods, and tools for sustainable product development. Nature-Inspired Design Strategies (NIDS) offer designers a distinct class of strategies that use ‘nature’ as a guiding source of knowledge and inspiration for addressing sustainability.

  8. The use of natural products for consumption in Denmark

    International Nuclear Information System (INIS)

    Strandberg, M.

    1996-05-01

    Through a questionnaire it was indicated that Danes use products from 'natural' ecosystems in an amount of approximately 2 kg per year. The most used products are berries and meat from game animals, whereas freshwater fish and wild mushrooms are less common in Danish kitchens. (au)

  9. World statistics on natural gas reserves, production and utilization

    International Nuclear Information System (INIS)

    Raikaslehto, S.

    2001-01-01

    By reviewing the statistics of BP Amoco on natural gas reserves, production and usage, it is easy to see that Russia and USA, both being large natural gas producers, differ significantly from each other. The natural gas reserves of USA are 6th largest in the world, simultaneously the natural gas consumption and import are largest in the world. About one third of the known natural gas reserves of the world are in Russia. The known natural gas reserves of both USA and Canada have decreases, but they have potential gas reserves left. Known natural gas reserves of the USA have been calculated to be sufficient for 9 years consumption at present usage and those of Canada for 11 years. The reserves of Algeria correspond to the usage of 55 years, and the Russian reserves for are about 83 years. Annual production figures of both Russia and the USA are nearly the same. Russia is the largest exporter (125.5 billion m 3 ) of natural gas and the USA the largest importer (96 billion m 3 ). The natural gas reserves of the largest European producers, the Netherlands and Norway have been estimated to be sufficient for use of about 20 years, but those of Great Britain only for about 10 years. The annual production of Russia has varied in the 1990s between nearly 600 billion m 3 and present 550 billion m 3 , the minimum being in 1997 only about 532 billion m 3 . Ten largest natural gas consumers use 67% of the natural gas consumed annually in the world. USA consumes about 27% of the total natural gas produced in the world, the amount of Russia being 364 billion m 3 (16%). Other large natural gas consumers are Great Britain, Germany, Japan, Ukraine, Canada, Italy, Iran and Uzbekistan. The share of these countries of the total consumption varied in between 2-4%. Only Japan has no natural gas production of its own. The foreign trade between Japan and Indonesia is trade on LNG. On the other hand the natural gas consumption of the world's 10th largest producer Norway is nearly zero, so

  10. Natural product-based nanomedicine: recent advances and issues

    Science.gov (United States)

    Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

    2015-01-01

    Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. PMID:26451111

  11. Essences in Metabolic Engineering of Lignan Biosynthesis

    Directory of Open Access Journals (Sweden)

    Honoo Satake

    2015-05-01

    Full Text Available Lignans are structurally and functionally diverse phytochemicals biosynthesized in diverse plant species and have received wide attentions as leading compounds of novel drugs for tumor treatment and healthy diets to reduce of the risks of lifestyle-related non-communicable diseases. However, the lineage-specific distribution and the low-amount of production in natural plants, some of which are endangered species, hinder the efficient and stable production of beneficial lignans. Accordingly, the development of new procedures for lignan production is of keen interest. Recent marked advances in the molecular and functional characterization of lignan biosynthetic enzymes and endogenous and exogenous factors for lignan biosynthesis have suggested new methods for the metabolic engineering of lignan biosynthesis cascades leading to the efficient, sustainable, and stable lignan production in plants, including plant cell/organ cultures. Optimization of light conditions, utilization of a wide range of elicitor treatments, and construction of transiently gene-transfected or transgenic lignan-biosynthesizing plants are mainly being attempted. This review will present the basic and latest knowledge regarding metabolic engineering of lignans based on their biosynthetic pathways and biological activities, and the perspectives in lignan production via metabolic engineering.

  12. Bioengineering natural product biosynthetic pathways for therapeutic applications.

    Science.gov (United States)

    Wu, Ming-Cheng; Law, Brian; Wilkinson, Barrie; Micklefield, Jason

    2012-12-01

    With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. A Growing Disconnection From Nature Is Evident in Cultural Products.

    Science.gov (United States)

    Kesebir, Selin; Kesebir, Pelin

    2017-03-01

    Human connection with nature is widely believed to be in decline even though empirical evidence is scarce on the magnitude and historical pattern of the change. Studying works of popular culture in English throughout the 20th century and later, we have documented a cultural shift away from nature that begins in the 1950s. Since then, references to nature have been decreasing steadily in fiction books, song lyrics, and film storylines, whereas references to the human-made environment have not. The observed temporal pattern is consistent with the explanatory role of increased virtual and indoors recreation options (e.g., television, video games) in the disconnect from nature, and it is inconsistent with a pure urbanization account. These findings are cause for concern, not only because they imply foregone physical and psychological benefits from engagement with nature, but also because cultural products are agents of socialization that can evoke curiosity, respect, and concern for the natural world.

  14. Deposits of naturally occurring radioactivity in production of oil and natural gas

    International Nuclear Information System (INIS)

    Strand, T.; Lysebo, I.; Kristensen, D.; Birovljev, A.

    1997-01-01

    Deposits of naturally occurring radioactive materials is an increasing problem in Norwegian oil and gas production. Activity concentration in solid-state samples and production water, and doses to workers involved in different operations off-shore, have been measured. The report also includes a discussion of different methods of monitoring and alternatives for final disposal of wastes. 154 refs

  15. Planning of optimum production from a natural gas field

    Energy Technology Data Exchange (ETDEWEB)

    Van Dam, J

    1968-03-01

    The design of an optimum development plan for a natural gas field always depends on the typical characteristics of the producing field, as well as those of the market to be served by this field. Therefore, a good knowledge of the field parameters, such as the total natural gas reserves, the well productivity, and the dependence of production rates on pipeline pressure and depletion of natural gas reserves, is required prior to designing the development scheme of the field, which in fact depends on the gas-sales contract to be concluded in order to commit the natural gas reserves to the market. In this paper these various technical parameters are discussed in some detail, and on this basis a theoretical/economical analysis of natural gas production is given. For this purpose a simplified economical/mathematical model for the field is proposed, from which optimum production rates at various future dates can be calculated. The results of these calculations are represented in a dimensionless diagram which may serve as an aid in designing optimum development plans for a natural gas field. The use of these graphs is illustrated in a few examples.

  16. Natural product-based nanomedicine: recent advances and issues

    Directory of Open Access Journals (Sweden)

    Watkins R

    2015-09-01

    Full Text Available Rebekah Watkins,1,2,* Ling Wu,1,* Chenming Zhang,3–5 Richey M Davis,3,5,6 Bin Xu1,3 1Department of Biochemistry, 2Program in Nanoscience, 3Center for Drug Discovery, 4Department of Biological Systems Engineering, 5Institute for Critical Technology and Applied Science, 6Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA *These authors contributed equally to this work Abstract: Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. Keywords: natural products, nanomedicine, drug delivery, bioavailability, targeting, controlled release

  17. The Traditional Medicine and Modern Medicine from Natural Products

    Directory of Open Access Journals (Sweden)

    Haidan Yuan

    2016-04-01

    Full Text Available Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.

  18. The Traditional Medicine and Modern Medicine from Natural Products.

    Science.gov (United States)

    Yuan, Haidan; Ma, Qianqian; Ye, Li; Piao, Guangchun

    2016-04-29

    Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.

  19. Culture-independent discovery of natural products from soil metagenomes.

    Science.gov (United States)

    Katz, Micah; Hover, Bradley M; Brady, Sean F

    2016-03-01

    Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately, traditional culture-based methods for natural product discovery have been deemphasized by pharmaceutical companies due in large part to high rediscovery rates. Culture-independent, or "metagenomic," methods, which rely on the heterologous expression of DNA extracted directly from environmental samples (eDNA), have the potential to provide access to metabolites encoded by a large fraction of the earth's microbial biosynthetic diversity. As soil is both ubiquitous and rich in bacterial diversity, it is an appealing starting point for culture-independent natural product discovery efforts. This review provides an overview of the history of soil metagenome-driven natural product discovery studies and elaborates on the recent development of new tools for sequence-based, high-throughput profiling of environmental samples used in discovering novel natural product biosynthetic gene clusters. We conclude with several examples of these new tools being employed to facilitate the recovery of novel secondary metabolite encoding gene clusters from soil metagenomes and the subsequent heterologous expression of these clusters to produce bioactive small molecules.

  20. Biotransformation and Production from Hansenula Anomala to Natural Ethyl Phenylacetate

    Directory of Open Access Journals (Sweden)

    Tian Xun

    2015-01-01

    Full Text Available Ethyl phenylacetate can be widely applied in many industries, such as food, medicines, cosmetics and medicinal herbs. At the moment, the production of natural ethyl phenylacetate is very limited. However, the biotransformation production of natural ethyl phenylacetate has an very extensive application prospect. This paper is written by taking the phenylacetic acid tolerance and the esterifying enzyme activity as the two indexes for screening the HA14 strain of hansenula anomala mutagenic which is regarded as the microorganism of ethyl phenylacetate production through biotransformation. By optimizing the production condition of phenylacetic acid and the esterification condition of ethyl phenylacetate, the production of ethyl phenylacetate accomplished through biotransformation within 72 hours can reach 864mg/L which is 171% of that of the initial bacterial strain.

  1. Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale.

    Science.gov (United States)

    Lemetre, Christophe; Maniko, Jeffrey; Charlop-Powers, Zachary; Sparrow, Ben; Lowe, Andrew J; Brady, Sean F

    2017-10-31

    Although bacterial bioactive metabolites have been one of the most prolific sources of lead structures for the development of small-molecule therapeutics, very little is known about the environmental factors associated with changes in secondary metabolism across natural environments. Large-scale sequencing of environmental microbiomes has the potential to shed light on the richness of bacterial biosynthetic diversity hidden in the environment, how it varies from one environment to the next, and what environmental factors correlate with changes in biosynthetic diversity. In this study, the sequencing of PCR amplicons generated using primers targeting either ketosynthase domains from polyketide biosynthesis or adenylation domains from nonribosomal peptide biosynthesis was used to assess biosynthetic domain composition and richness in soils collected across the Australian continent. Using environmental variables collected at each soil site, we looked for environmental factors that correlated with either high overall domain richness or changes in the domain composition. Among the environmental variables we measured, changes in biosynthetic domain composition correlate most closely with changes in latitude and to a lesser extent changes in pH. Although it is unclear at this time the exact mix of factors that may drive the relationship between biosynthetic domain composition and latitude, from a practical perspective the identification of a latitudinal basis for differences in soil metagenome biosynthetic domain compositions should help guide future natural product discovery efforts. Published under the PNAS license.

  2. World natural gas supply and demand: Brief pause in production

    International Nuclear Information System (INIS)

    Coccia, G.

    1993-01-01

    With reference to the 1992 CEDIGAZ (Centre International sur le Gas Naturel et tous Hydrocarbures Gazeux) report on world natural gas supply and demand, this paper assesses current market and production trends in this industry. The slight drop in production in 1992, the first which has which has occurred after many consecutive years of steady increases, is ascribed to ownership disputes among the former-USSR republics and major changes in the organizational structure of the former-USSR's natural gas industry. Strong increases in demand are forecasted due to expected strong population growth and increased industrialization to take place in China and India. Price trends in natural gas should remain steady as a result of plentiful supplies of this fuel and coal, a major competitor. The use of relatively clean natural gas is suggested as a practical alternative to energy taxes now being proposed as a means for the reduction of greenhouse gas emissions

  3. Radon gas in oil and natural gas production facilities

    International Nuclear Information System (INIS)

    Chandler, W.P.

    1994-01-01

    Radon gas is a naturally occurring radionuclide that can be found in some oil and natural gas production facilities, either as a contaminant in a natural gas stream or derived from Radium dissolved in formation waters. The gas itself is not normally a health hazard, but it's decay products, which can be concentrated by plate-out or deposition as a scale in process equipment, can be a health hazard for maintenance personnel. To evaluate possible health hazards, it is necessary to monitor for naturally occurring radioactive materials (NORM) in the gas stream and in the formation water. If Radon and/or Radium is found, a monitoring programme should be initiated to comply with National or State requirements. In some instances, it has been found necessary to dispose of silt and scale materials as low level radioactive waste. 8 refs

  4. Bioactive natural products from Chinese marine flora and fauna.

    Science.gov (United States)

    Zhou, Zhen-Fang; Guo, Yue-Wei

    2012-09-01

    In recent decades, the pharmaceutical application potential of marine natural products has attracted much interest from both natural product chemists and pharmacologists. Our group has long been engaged in the search for bioactive natural products from Chinese marine flora (such as mangroves and algae) and fauna (including sponges, soft corals, and mollusks), resulting in the isolation and characterization of numerous novel secondary metabolites spanning a wide range of structural classes and various biosynthetic origins. Of particular interest is the fact that many of these compounds show promising biological activities, including cytotoxic, antibacterial, and enzyme inhibitory effects. By describing representative studies, this review presents a comprehensive summary regarding the achievements and progress made by our group in the past decade. Several interesting examples are discussed in detail.

  5. Dereplication of Microbial Natural Products by LC-DAD-TOFMS

    DEFF Research Database (Denmark)

    Nielsen, Kristian Fog; Månsson, Maria; Rank, Christian

    2011-01-01

    Dereplication, the rapid identification of known compounds present in a mixture, is crucial to the fast discovery of novel natural products. Determining the elemental composition of compounds in mixtures and tentatively identifying natural products using MS/MS and UV/vis spectra is becoming easier...... with advances in analytical equipment and better compound databases. Here we demonstrate the use of LC-UV/vis-MS-based dereplication using data from UV/vis diode array detection and ESI+/ESI– time-of-flight MS for assignment of 719 microbial natural product and mycotoxin reference standards. ESI+ was the most...... unambiguously using multiple adduct ions, while a further 41% of the compounds were detected only as [M – H]−. The most reliable interpretations of conflicting ESI+ and ESI– data on a chromatographic peak were from the ionization polarity with the most intense ionization. Poor ionization was most common...

  6. Anti-cancer natural products isolated from chinese medicinal herbs

    Directory of Open Access Journals (Sweden)

    Wu Guosheng

    2011-07-01

    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  7. Natural radionuclide distribution in phosphate fertilizer and superphosphate production technology

    Energy Technology Data Exchange (ETDEWEB)

    Lisachenko, Eh P; Ponikarova, T M; Lisitsyna, Yu Z

    1987-01-01

    The obtained data on the natural radionuclide distribution by phosphate fertilizer and superphosphate production process stages testify to phosphate fertilizer enrichment 2-4 times in relation to initial ore, depending in the raw material used. In this case uranium and thorium series element concentration value (in equilibrium with their decomposition products), proposed as a regulating one in phosphorus-containing fertilizers, is not achieved. However, the fact of lurichment as it is and the enrichment factor, stated in the course of the work, should be taken into account for evaluation of phosphorite new deposit raw material with higher concentrations of natural radionuclides. Natural radionuclide separation in the enrichment process and superphosphate production is not revealed.

  8. α-Haloaldehydes: versatile building blocks for natural product synthesis.

    Science.gov (United States)

    Britton, Robert; Kang, Baldip

    2013-02-01

    The diastereoselective addition of organometallic reagents to α-chloroaldehydes was first reported in 1959 and occupies a historically significant role as the prototypical reaction for Cornforth's model of stereoinduction. Despite clear synthetic potential for these reagents, difficulties associated with producing enantiomerically enriched α-haloaldehydes limited their use in natural product synthesis through the latter half of the 20th century. In recent years, however, a variety of robust, organocatalytic processes have been reported that now provide direct access to optically enriched α-haloaldehydes and have motivated renewed interest in their use as building blocks for natural product synthesis. This Highlight summarizes the methods available for the enantioselective preparation of α-haloaldehydes and their stereoselective conversion into natural products.

  9. Search for bioactive natural products from medicinal plants of Bangladesh.

    Science.gov (United States)

    Ahmed, Firoj; Sadhu, Samir Kumar; Ishibashi, Masami

    2010-10-01

    In our continuous search for bioactive natural products from natural resources, we explored medicinal plants of Bangladesh, targeting cancer-related tumor necrosis factor-related apoptosis-inducing ligand-signaling pathway, along with some other biological activities such as prostaglandin inhibitory activity, 1,1-diphenyl-2-picrylhydrazyl free-radical-scavenging activity, and cell growth inhibitory activity. Along with this, we describe a short field study on Sundarbans mangrove forests, Bangladesh, in the review.

  10. Knowledge based decision making: perspective on natural gas production

    Energy Technology Data Exchange (ETDEWEB)

    Ydstie, B. Erik; Stuland, Kjetil M.

    2009-07-01

    Conclusions (drawn by the author): Decarbonization of energy sources - From coal to renewable. Natural Gas Abundantly available - Norway is no. 3 exporter. Natural gas important as - Hydrogen source for chemicals; - Electricity; - End consumer usage (heating etc). Large potential for application of model based decision making; - Where and when to install platforms and drill wells - How to operate platforms and pipeline systems; - How to operate and optimize chemical production; - Optimization of electricity generation systems. (author)

  11. Exposures from consumption of agricultural and semi-natural products

    International Nuclear Information System (INIS)

    Strand, P.; Skuterud, L.; Balonov, M.; Travnikova, I.; Hove, K.; Howard, B.; Prister, B.S.; Ratnikov, A.

    1996-01-01

    The importance of food from different production systems to the internal dose from radiocesium, was investigated in selected study sites in Ukraine and Russia. Food products from semi-natural ecosystems are major contributors to the individual internal dose to rural population in areas affected by the Chernobyl accident. At the selected study sites it is estimated in 1995 that foods from private farms and forests contribute on average 35% to 60%, to the individual internal dose, variation relating to soil types and implemented countermeasures. The importance of food products from private farms and particularly forest products increases with time since Cs concentration in some of the natural food products have longer ecological half life than food products from agricultural systems. A significant relationship was observed between consumption of mushrooms and whole body content of radiocesium in rural people. The contribution to the collective dose of food products produced in the semi-natural ecosystems is less than the contribution to the individual internal dose for the local rural population

  12. LC-NMR: profiling and dereplication of natural product extracts

    International Nuclear Information System (INIS)

    Urban, Sylvia

    2006-01-01

    Natural products have served as a major source of drugs for centuries, with over half of the pharmaceuticals in use today derived from natural origins. Natural products continue to play a dominant role in the discovery of leads for the development of drugs for the treatment of human diseases. Much remains to be explored, particularly the marine and microbial environments, from which a host of novel bioactive chemical entities await discovery. The search for new drugs from natural origins (either terrestrial or marine) involves screening of extracts for the presence of novel compounds and an investigation of their biological activities. Suspected novel or bioactive compounds are usually isolated to elucidate the structure and for further biological and toxicological testing. The path that leads from the intact terrestrial or marine organism to the pure constituents is long, involving work that might last from weeks to years. Recognition of natural products at the earliest possible stage of separation is known as dereplication and is essential to avoid the time-consuming isolation of common constituents and nuisance compounds. In the search for new natural products, crude extracts are typically subjected to multi-step work-up and isolation procedures, which include various separation methods, in order to obtain pure compounds whose structure is then elucidated using off-line spectroscopic methods such as nuclear magnetic resonance (NMR) and mass spectroscopy (MS). The characterisation of a natural product can be summarised by the information obtained from each of the individual spectroscopic techniques. With the application of one or more of these individual techniques a dereplication by partial characterisation is possible. As natural product extracts often contain a large number of closely related, and thus difficult to separate, compounds, this classical approach may become very tedious and time-consuming. The characterisation of natural products in complex

  13. Marine Natural Products as Models to Circumvent Multidrug Resistance

    Directory of Open Access Journals (Sweden)

    Solida Long

    2016-07-01

    Full Text Available Multidrug resistance (MDR to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC transporter P-glycoprotein (P-gp, which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

  14. Marine actinobacteria: an important source of bioactive natural products.

    Science.gov (United States)

    Manivasagan, Panchanathan; Kang, Kyong-Hwa; Sivakumar, Kannan; Li-Chan, Eunice C Y; Oh, Hyun-Myung; Kim, Se-Kwon

    2014-07-01

    Marine environment is largely an untapped source for deriving actinobacteria, having potential to produce novel, bioactive natural products. Actinobacteria are the prolific producers of pharmaceutically active secondary metabolites, accounting for about 70% of the naturally derived compounds that are currently in clinical use. Among the various actinobacterial genera, Actinomadura, Actinoplanes, Amycolatopsis, Marinispora, Micromonospora, Nocardiopsis, Saccharopolyspora, Salinispora, Streptomyces and Verrucosispora are the major potential producers of commercially important bioactive natural products. In this respect, Streptomyces ranks first with a large number of bioactive natural products. Marine actinobacteria are unique enhancing quite different biological properties including antimicrobial, anticancer, antiviral, insecticidal and enzyme inhibitory activities. They have attracted global in the last ten years for their ability to produce pharmaceutically active compounds. In this review, we have focused attention on the bioactive natural products isolated from marine actinobacteria, possessing unique chemical structures that may form the basis for synthesis of novel drugs that could be used to combat resistant pathogenic microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. In Vitro Biosynthesis of Unnatural Enterocin and Wailupemycin Polyketides¥

    Science.gov (United States)

    Kalaitzis, John A.; Cheng, Qian; Thomas, Paul M.; Kelleher, Neil L.; Moore, Bradley S.

    2009-01-01

    Nature has evolved finely tuned strategies to synthesize rare and complex natural products such as the enterocin family of polyketides from the marine bacterium Streptomyces maritimus. Herein we report the directed ex vivo multienzyme syntheses of 24 unnatural 5-deoxyenterocin and wailupemycin F and G analogues, 18 of which are new. We have generated molecular diversity by priming the enterocin biosynthesis enzymes with unnatural substrates and have illustrated further the uniqueness of this type II polyketide synthase by way of exploiting its unusual starter unit biosynthesis pathways. PMID:19215142

  16. Natural product terpenoids in Eocene and Miocene conifer fossils.

    Science.gov (United States)

    Otto, Angelika; White, James D; Simoneit, Bernd R T

    2002-08-30

    Numerous saturated and aromatic hydrocarbons, but not polar compounds, originating from plants and microorganisms (biomarkers) have been reported in sediments, coals, and petroleum. Here we describe natural product terpenoids found in two fossil conifers, Taxodium balticum (Eocene) and Glyptostrobus oregonensis (Miocene). A similar terpenoid pattern is also observed in extant Taxodium distichum. The preservation of characteristic terpenoids (unaltered natural products) in the fossil conifers supports their systematic assignment to the Cypress family (Cupressaceae sensu lato). The results also show that fossil conifers can contain polar terpenoids, which are valuable markers for (paleo)chemosystematics and phylogeny.

  17. Synthesis and Biological Investigation of Antioxidant Pyrrolomorpholine Spiroketal Natural Products

    Science.gov (United States)

    Verano, Alyssa Leigh

    The pyrrolomorpholine spiroketal natural product family is comprised of epimeric furanose and pyranose isomers. These compounds were isolated from diverse plant species, all of which are used as traditional Chinese medicines for the treatment of a variety of diseases. Notably, the spiroketal natural products acortatarins A and B exhibit antioxidant activity in a diabetic renal cell model, significantly attenuating hyperglycemia-induced production of reactive oxygen species (ROS), a hallmark of diabetic nephropathy. The xylapyrrosides, additional members of the family, also inhibit t-butyl hydroperoxide-induced cytotoxicity in rat vascular smooth muscle cells. Accordingly, these natural products have therapeutic potential for the treatment of oxidative stress-related pathologies, and synthetic access would provide an exciting opportunity to investigate bioactivity and mechanism of action. Herein, we report the stereoselective synthesis of acortatarins A and B, furanose members of the pyrrolomorpholine spiroketal family. Our synthetic route was expanded to synthesize the pyranose congeners, thus completing entire D-enantiomeric family of natural products. Efficient access towards these scaffolds enabled systematic analogue synthesis, investigation of mechanism-of-action, and the discovery of novel antioxidants.

  18. European energy security: The future of Norwegian natural gas production

    International Nuclear Information System (INIS)

    Soederbergh, Bengt; Jakobsson, Kristofer; Aleklett, Kjell

    2009-01-01

    The European Union (EU) is expected to meet its future growing demand for natural gas by increased imports. In 2006, Norway had a 21% share of EU gas imports. The Norwegian government has communicated that Norwegian gas production will increase by 25-40% from today's level of about 99 billion cubic meters (bcm)/year. This article shows that only a 20-25% growth of Norwegian gas production is possible due to production from currently existing recoverable reserves and contingent resources. A high and a low production forecast for Norwegian gas production is presented. Norwegian gas production exported by pipeline peaks between 2015 and 2016, with minimum peak production in 2015 at 118 bcm/year and maximum peak production at 127 bcm/year in 2016. By 2030 the pipeline export levels are 94-78 bcm. Total Norwegian gas production peaks between 2015 and 2020, with peak production at 124-135 bcm/year. By 2030 the production is 96-115 bcm/year. The results show that there is a limited potential for increased gas exports from Norway to the EU and that Norwegian gas production is declining by 2030 in all scenarios. Annual Norwegian pipeline gas exports to the EU, by 2030, may even be 20 bcm lower than today's level.

  19. An innovative model for regulating supplement products: Natural health products in Canada

    International Nuclear Information System (INIS)

    Nestmann, Earle R.; Harwood, Melody; Martyres, Stephanie

    2006-01-01

    On 1 January 2004, Health Canada officially added a new term to the global list of synonyms for dietary supplements: natural health products (NHP). Developed with the intent of providing Canadian consumers with ready access to NHP that are safe, effective, and of high quality, the Natural Health Products Regulations (the NHP regulations) are applicable to the sale, manufacture, packaging, labelling, importation, distribution, and storage of NHP, and are administered by the recently formed Natural Health Products Directorate (NHPD) within Health Canada. This paper provides an overview of the process for regulating supplement products in Canada

  20. Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

    Science.gov (United States)

    Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

    2015-01-01

    Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.

  1. Liquefied natural gas production at Hammerfest: A transforming marine community

    NARCIS (Netherlands)

    Bets, van L.K.J.; Tatenhove, van J.P.M.; Mol, A.P.J.

    2016-01-01

    Global energy demand and scarce petroleum resources require communities to adapt to a rapidly changing Arctic environment, but as well to a transforming socio-economic environment instigated by oil and gas development. This is illustrated by liquefied natural gas production by Statoil at Hammerfest,

  2. Chemistry of natural products: A veritable approach to the ...

    African Journals Online (AJOL)

    Even with the advent of newer technologies such as combinatorial chemistry, robotics, high throughput screening (HTS), bioinformatics, and in silico molecular modelling, natural products still play a crucial role in drug discovery. This is because they provide an unparalleled range of chemical diversity on which the newer ...

  3. Natural Products Research in China from 2015 to 2016

    Science.gov (United States)

    Liu, Haishan; Zhu, Guoliang; Fan, Yaqin; Du, Yuqi; Lan, Mengmeng; Xu, Yibo; Zhu, Weiming

    2018-03-01

    This review covers the literature published by Chinese chemists from 2015 to 2016 on natural products (NPs), with 1,985 citations referring to 6,944 new compounds isolated from marine or terrestrial microorganisms, plants, and animals. The emphasis is on 730 new compounds with a novel skeleton or/and significant bioactivity, together with their source organism and country of origin.

  4. Low Carbon Technology Options for the Natural Gas Electricity Production

    Science.gov (United States)

    The ultimate goal of this task is to perform environmental and economic analysis of natural gas based power production technologies (different routes) to investigate and evaluate strategies for reducing emissions from the power sector. It is a broad research area. Initially, the...

  5. Learning Organic Chemistry Through Natural Products A Practical ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 9. Learning Organic Chemistry Through Natural Products A Practical Approach. N R Krishnaswamy. Series Article Volume 1 Issue 9 September 1996 pp 25-33. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Natural gas for power production in Western Europe

    International Nuclear Information System (INIS)

    1993-01-01

    The third and last part of the Sub-Committee's study on natural gas for power generation is reprinted in this issue. This part addresses gas consumption in electricity production until the year 2010. The first part of the study dealing with combined cycle power plants was published in September and the 2nd part on regulatory and environmental issues in October 1992

  7. Short history of natural product research in the CSIR

    CSIR Research Space (South Africa)

    Walwyn, D

    2006-02-01

    Full Text Available Natural product research has been a major component of the CSIR's bioscience activities for its entire history, and particularly in the 1960s and 1970s. This type of work is also strongly aligned with one of the objectives of the CSIR, namely...

  8. The sustainable management of a productive natural capital

    DEFF Research Database (Denmark)

    Daubanes, Julien Xavier

    is relevant, among other examples, to the case of naturebased tourism. I study the sustainable management of a productive natural capital: the conditions under which its exploitation generates maximum long-run social benefits; the various ways in which a regulator can implement such an exploitation; the rent...

  9. Natural product derived insecticides: discovery and development of spinetoram.

    Science.gov (United States)

    Galm, Ute; Sparks, Thomas C

    2016-03-01

    This review highlights the importance of natural product research and industrial microbiology for product development in the agricultural industry, based on examples from Dow AgroSciences. It provides an overview of the discovery and development of spinetoram, a semisynthetic insecticide derived by a combination of a genetic block in a specific O-methylation of the rhamnose moiety of spinosad coupled with neural network-based QSAR and synthetic chemistry. It also emphasizes the key role that new technologies and multidisciplinary approaches play in the development of current spinetoram production strains.

  10. Gamma radiodecontamination of natural products uses in Cuban pharmaceutical industry

    International Nuclear Information System (INIS)

    Rodriguez, M.; Lopez, M.; Guerra, M.; Lastra, H.; Prieto, E.; Padron, E.

    1997-01-01

    The aim of the present paper was to carry out the gamma radiodecontamination of industrial productions from there medicinal plant species (C. officinalis, P. incarta and M. recuttia) and two pharmaceuticals forms (S. platensis and bee pollen tabs) which presented high levels of microbiological count. Adequate irradiation doses calculated for each product were used in decontamination. The results obtained showed the effectiveness of the process in the elimination of microbial contamination from theses natural products. No changes in nutritional constituents or physico-chemical properties were observed

  11. Exploitation of Aspergillus terreus for the Production of Natural Statins

    Directory of Open Access Journals (Sweden)

    Mishal Subhan

    2016-04-01

    Full Text Available The fungus Aspergillus (A. terreus has dominated the biological production of the “blockbuster” drugs known as statins. The statins are a class of drugs that inhibit HMG-CoA reductase and lead to lower cholesterol production. The statins were initially discovered in fungi and for many years fungi were the sole source for the statins. At present, novel chemically synthesised statins are produced as inspired by the naturally occurring statin molecules. The isolation of the natural statins, compactin, mevastatin and lovastatin from A. terreus represents one of the great achievements of industrial microbiology. Here we review the discovery of statins, along with strategies that have been applied to scale up their production by A. terreus strains. The strategies encompass many of the techniques available in industrial microbiology and include the optimization of media and fermentation conditions, the improvement of strains through classical mutagenesis, induced genetic manipulation and the use of statistical design.

  12. Natural products - plenty more where that came from

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, M.

    1980-12-22

    In this article, natural products and their possible use as renewable resources are reviewed. The fermentation of corn for the production of alcohol for motor fuel is discussed and other crops for this purpose include sugar cane, cassava, sweet potato and Jerusalem artichoke. The hydrolysis of cellulose to sugars based on enzyme hydrolysis is currently being researched in the USA. Also in the USA, Melvin Calvin hopes to breed a rubber-bearing plant whose latex can be easily cracked to motor fuel. Guayule and jojoba rubber-bearing plants are also the focus of research at present. The importance of natural vegetation in the manufacturing of medicines and in the chemical and food industries is stressed. Finally products of the sea, particularly alginates and carragheenins are mentioned, but as yet, the full potential of the sea to yield renewable resources is unknown.

  13. Natural radioactivity and estimated dose in Brazilian tobacco products

    International Nuclear Information System (INIS)

    Oliveira, Aline S.G.R. de; Damatto, Sandra R.

    2017-01-01

    Tobacco products contain significant concentrations of natural radionuclides from 238 U and 232 Th series. The consumption of these products increases the internal dose of radiation due to the inhalation of the natural radionuclides. Studies from literature emphasize that tobacco products have measurable concentrations of 210 Po and 210 Pb, and may contribute significantly to the increase of internal radiation dose and a large number of lung cancer in smokers. The objectives of this work were to determine the concentrations (Bq/kg) of the radionuclides 226 Ra, 228 Ra, 210 Pb and 210 Po and calculate the internal doses of radiation due to the consumption of these products. In the present work 71 samples were analyzed, consisting of cigars, unflavored and flavored cigarettes, straw cigarettes, cigars and roll smoke. The samples were purchased in Brazilian popular commercial establishments. The analytical techniques employed were the gross alpha and beta measurement after radiochemical separation for the radionuclides 226 Ra, 228 Ra, 210 Pb and alpha spectrometry for 210 Po. The internal radiation doses were calculated with the activity concentrations determined and using the ICRP Publication 119 dose coefficients. An annual consumption of 3,650 kg of tobacco products was considered. The inhalation rates of each radionuclide followed the rates of the current literature. The estimated mean annual dose varied from 76 to 263μSv/y for the tobacco product studied in this work. (author)

  14. Natural radioactivity and estimated dose in Brazilian tobacco products

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Aline S.G.R. de; Damatto, Sandra R., E-mail: aline.oliveira@ipen.br, E-mail: damatto@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Tobacco products contain significant concentrations of natural radionuclides from {sup 238}U and {sup 232}Th series. The consumption of these products increases the internal dose of radiation due to the inhalation of the natural radionuclides. Studies from literature emphasize that tobacco products have measurable concentrations of {sup 210}Po and {sup 210}Pb, and may contribute significantly to the increase of internal radiation dose and a large number of lung cancer in smokers. The objectives of this work were to determine the concentrations (Bq/kg) of the radionuclides {sup 226}Ra, {sup 228}Ra, {sup 210}Pb and {sup 210}Po and calculate the internal doses of radiation due to the consumption of these products. In the present work 71 samples were analyzed, consisting of cigars, unflavored and flavored cigarettes, straw cigarettes, cigars and roll smoke. The samples were purchased in Brazilian popular commercial establishments. The analytical techniques employed were the gross alpha and beta measurement after radiochemical separation for the radionuclides {sup 226}Ra, {sup 228}Ra, {sup 210}Pb and alpha spectrometry for {sup 210}Po. The internal radiation doses were calculated with the activity concentrations determined and using the ICRP Publication 119 dose coefficients. An annual consumption of 3,650 kg of tobacco products was considered. The inhalation rates of each radionuclide followed the rates of the current literature. The estimated mean annual dose varied from 76 to 263μSv/y for the tobacco product studied in this work. (author)

  15. Production of New Cladosporin Analogues by Reconstitution of the Polyketide Synthases Responsible for the Biosynthesis of this Antimalarial Agent.

    Science.gov (United States)

    Cochrane, Rachel V K; Sanichar, Randy; Lambkin, Gareth R; Reiz, Béla; Xu, Wei; Tang, Yi; Vederas, John C

    2016-01-11

    The antimalarial agent cladosporin is a nanomolar inhibitor of the Plasmodium falciparum lysyl-tRNA synthetase, and exhibits activity against both blood- and liver-stage infection. Cladosporin can be isolated from the fungus Cladosporium cladosporioides, where it is biosynthesized by a highly reducing (HR) and a non-reducing (NR) iterative type I polyketide synthase (PKS) pair. Genome sequencing of the host organism and subsequent heterologous expression of these enzymes in Saccharomyces cerevisiae produced cladosporin, confirming the identity of the putative gene cluster. Incorporation of a pentaketide intermediate analogue indicated a 5+3 assembly by the HR PKS Cla2 and the NR PKS Cla3 during cladosporin biosynthesis. Advanced-intermediate analogues were synthesized and incorporated by Cla3 to furnish new cladosporin analogues. A putative lysyl-tRNA synthetase resistance gene was identified in the cladosporin gene cluster. Analysis of the active site emphasizes key structural features thought to be important in resistance to cladosporin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Interdisciplinary researches for potential developments of drugs and natural products

    Directory of Open Access Journals (Sweden)

    Arunrat Chaveerach

    2017-04-01

    Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.

  17. Interdisciplinary researches for potential developments of drugs and natural products

    Institute of Scientific and Technical Information of China (English)

    Arunrat Chaveerach; Runglawan Sudmoon; Tawatchai Tanee

    2017-01-01

    Developments of drugs or natural products from plants are possibly made,simple to use and lower cost than modern drugs.The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas,such as foods,traditional medicine,fragrances and seasonings.Then those data will be associated with scientific researches,namely plant collection and identification,phytochemical screening by gas chromatography-mass spectrometry,pharmacological study/review for their functions,and finally safety and efficiency tests in human.For safety testing,in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed.When active chemicals and functions containing plants were chosen with safety and efficacy for human uses,then,the potential medicinal natural products will be produced.Based on these procedures,the producing cost will be cheaper and the products can be evaluated for their clinical properties.Thus,the best and lowest-priced medicines and natural products can be distributed worldwide.

  18. Monoterpene biosynthesis potential of plant subcellular compartments

    NARCIS (Netherlands)

    Dong, L.; Jongedijk, E.J.; Bouwmeester, H.J.; Krol, van der A.R.

    2016-01-01

    Subcellular monoterpene biosynthesis capacity based on local geranyl diphosphate (GDP) availability or locally boosted GDP production was determined for plastids, cytosol and mitochondria. A geraniol synthase (GES) was targeted to plastids, cytosol, or mitochondria. Transient expression in Nicotiana

  19. Biosynthesis and Characterization of Silver Nanoparticles by Aspergillus Species

    Science.gov (United States)

    Pourshahid, Seyedmohammad; Mehryar, Pouyan; Pakshir, Keyvan; Rahimi, Mohammad Javad; Arabi Monfared, Ali

    2016-01-01

    Currently, researchers turn to natural processes such as using biological microorganisms in order to develop reliable and ecofriendly methods for the synthesis of metallic nanoparticles. In this study, we have investigated extracellular biosynthesis of silver nanoparticles using four Aspergillus species including A. fumigatus, A. clavatus, A. niger, and A. flavus. We have also analyzed nitrate reductase activity in the studied species in order to determine the probable role of this enzyme in the biosynthesis of silver nanoparticles. The formation of silver nanoparticles in the cell filtrates was confirmed by the passage of laser light, change in the color of cell filtrates, absorption peak at 430 nm in UV-Vis spectra, and atomic force microscopy (AFM). There was a logical relationship between the efficiencies of studied Aspergillus species in the production of silver nanoparticles and their nitrate reductase activity. A. fumigatus as the most efficient species showed the highest nitrate reductase activity among the studied species while A. flavus exhibited the lowest capacity in the biosynthesis of silver nanoparticles which was in accord with its low nitrate reductase activity. The present study showed that Aspergillus species had potential for the biosynthesis of silver nanoparticles depending on their nitrate reductase activity. PMID:27652264

  20. A plug-and-play pathway refactoring workflow for natural product research in Escherichia coli and Saccharomyces cerevisiae.

    Science.gov (United States)

    Ren, Hengqian; Hu, Pingfan; Zhao, Huimin

    2017-08-01

    Pathway refactoring serves as an invaluable synthetic biology tool for natural product discovery, characterization, and engineering. However, the complicated and laborious molecular biology techniques largely hinder its application in natural product research, especially in a high-throughput manner. Here we report a plug-and-play pathway refactoring workflow for high-throughput, flexible pathway construction, and expression in both Escherichia coli and Saccharomyces cerevisiae. Biosynthetic genes were firstly cloned into pre-assembled helper plasmids with promoters and terminators, resulting in a series of expression cassettes. These expression cassettes were further assembled using Golden Gate reaction to generate fully refactored pathways. The inclusion of spacer plasmids in this system would not only increase the flexibility for refactoring pathways with different number of genes, but also facilitate gene deletion and replacement. As proof of concept, a total of 96 pathways for combinatorial carotenoid biosynthesis were built successfully. This workflow should be generally applicable to different classes of natural products produced by various organisms. Biotechnol. Bioeng. 2017;114: 1847-1854. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Total Syntheses of Polycyclic Polyprenylated Acylphloroglucinol Natural Products and Analogs Utilizing Alkylative Dearomatizations and Cationic Cyclizations

    Science.gov (United States)

    Boyce, Jonathan H.

    Polycyclic polyprenylated acylphloroglucinols (PPAPs) are structurally complex natural products with promising biological activities. These compounds have interesting anticancer and anti-HIV properties as well as other biological activities making them highly attractive synthetic targets. We report a stereodivergent, asymmetric total synthesis of (-)-clusianone in six steps from commercial materials. We have implemented a challenging cationic cyclization forging a bond between two sterically encumbered quaternary carbon atoms. Mechanistic studies point to the unique ability of formic acid to mediate the cyclization forming the clusianone framework. We also present a biosynthesis-inspired, diversity-oriented synthesis approach for rapid construction of PPAP analogs via palladium-catalyzed dearomative conjunctive allylic alkylation (DCAA). These efficient palladium-catalyzed protocols construct the [3.3.1]-bicyclic PPAP core in a single step from their stable aromatic precursors. The first syntheses of 13,14-didehydroxyisogarcinol and garcimultiflorone A stereoisomers are reported in six steps from a commercially available phloroglucinol. Lewis acid-controlled, diastereoselective cationic oxycyclizations enabled asymmetric syntheses of (-)-6-epi-13,14-didehydroxyisogarcinol and (+)-30-epi-13,14-didehydroxyisogarcinol. A similar strategy enabled production of the meso-derived isomers (+/-)-6,30- epi-13,14-didehydroxyisogarcinol and (+/-)-6,30-epi -garcmultiflorone A. A convenient strategy for gram scale synthesis of these stereoisomers was developed utilizing diastereomer separation at a later stage in the synthesis that minimized the number of necessary synthetic operations to access all possible stereoisomers. Finally, we report cationic rearrangements of dearomatized acylphloroglucinols leading to the formation of unprecedented PPAP scaffolds. A novel type A [3.3.1]-bicyclic PPAP was produced as a major product and the structure confirmed by X-ray crystallographic

  2. Dietary Natural Products for Prevention and Treatment of Breast Cancer.

    Science.gov (United States)

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-07-08

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

  3. Marine natural products: a new wave of drugs?

    Science.gov (United States)

    Montaser, Rana; Luesch, Hendrik

    2011-01-01

    The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future. PMID:21882941

  4. What Is the Structure of the Antitubercular Natural Product Eucapsitrione?

    Science.gov (United States)

    Pullella, Glenn A; Wild, Duncan A; Nealon, Gareth L; Elyashberg, Mikhail; Piggott, Matthew J

    2017-07-21

    1,5,7-Trihydroxy-6H-indeno[1,2-b]anthracene-6,11,13-trione (1), proposed to be the antitubercular natural product eucapsitrione, has been synthesized in 43% overall yield and six steps, including a key Suzuki-Miyaura biaryl coupling and a directed remote metalation (DReM)-initiated cyclization. The physical and spectroscopic properties of 1 do not match the data reported for the natural product. At this time there is insufficient information available to enable a structure reassignment. During the optimization of the Suzuki-Miyaura coupling, an unprecedented biaryl coupling ortho to the borono group was observed. The scope of this unusual reaction has been investigated.

  5. Challenges and solutions in natural gas engine development and productions

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadi, Mahdi; Izanloo, Hossein [Irankhodro Powertrain Co. (IPCO) (Iran)

    2008-07-01

    As an alternative fuel, natural gas is generally accepted for internal combustion engines and some developments have been conducted in order to adopt it for the road vehicles and stationary applications. Foresights shows natural gas vehicles will be a part of the future transportation technology regarding to their mid and long-term benefits. Therefore inherent problems of natural gas engine technology should be overcome to produce a competitive engine. In this paper major problems and their possible solutions in developing and producing natural gas engine for passenger cars are detailed and discussed. Challenging materials are sorted and presented in two categorizes: technical and econo-strategical problems. In the technical section major difficulties faced in components or systems of natural gas engine are analysed in different aspects of design, validation, and production. In addition problems arisen from the fuel characteristics which influence the function and durability of engine are argued. Subjects like freezing in gas regulator, cold start fuel injection, gas leakage, impurities within compressed natural gas, variation in fuel composition, thermo-mechanics of cylinder head and block, wear of valve seat inserts, spark plug erosion, back-fire phenomenon, engine oil quality requirement, low power density and mileage are described. In the econo-strategical discussion, challenges like limited gas distribution infrastructure, lack of specific manufacturing standards and codes, and non-dedicated emission standards are explained. In both part of the paper a comprehensive view is extended to clarify the effect, risk and solutions of each problem. Due to the fact that almost all information and analysis presented in this paper are based on the experience of developing a natural gas engine family, and an extensive literature review, discussions and conclusions could be useful as a guide line for future natural gas engine projects. (orig.)

  6. The Production and Utilization of GDP-glucose in the Biosynthesis of Trehalose 6-Phosphate by Streptomyces venezuelae.

    Science.gov (United States)

    Asención Diez, Matías D; Miah, Farzana; Stevenson, Clare E M; Lawson, David M; Iglesias, Alberto A; Bornemann, Stephen

    2017-01-20

    Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilize ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudoglycosyltransferase enzyme. Comparison of the donor binding sites reveals that the amino acids associated with the binding of diphosphoribose are almost all identical in these three enzymes. By contrast, the amino acids associated with binding guanine in VldE (Asn, Thr, and Val) are similar in S. venezuelae OtsA (Asp, Ser, and Phe, respectively) but not conserved in E. coli OtsA (His, Leu, and Asp, respectively), providing a rationale for the purine base specificity of S. venezuelae OtsA. To establish which donor is used in vivo, we generated an otsA null mutant in S. venezuelae The mutant had a cell density-dependent growth phenotype and accumulated galactose 1-phosphate, glucose 1-phosphate, and GDP-glucose when grown on galactose. To determine how the GDP-glucose is generated, we characterized three candidate GDP-glucose pyrophosphorylases. SVEN_3027 is a UDP-glucose pyrophosphorylase, SVEN_3972 is an unusual ITP-mannose pyrophosphorylase, and SVEN_2781 is a pyrophosphorylase that is capable of generating GDP-glucose as well as GDP-mannose. We have therefore established how S. venezuelae can make and utilize GDP-glucose in the biosynthesis of trehalose 6-phosphate. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. The Production and Utilization of GDP-glucose in the Biosynthesis of Trehalose 6-Phosphate by Streptomyces venezuelae*

    Science.gov (United States)

    Asención Diez, Matías D.; Miah, Farzana; Stevenson, Clare E. M.; Lawson, David M.; Iglesias, Alberto A.; Bornemann, Stephen

    2017-01-01

    Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilize ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli. However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudoglycosyltransferase enzyme. Comparison of the donor binding sites reveals that the amino acids associated with the binding of diphosphoribose are almost all identical in these three enzymes. By contrast, the amino acids associated with binding guanine in VldE (Asn, Thr, and Val) are similar in S. venezuelae OtsA (Asp, Ser, and Phe, respectively) but not conserved in E. coli OtsA (His, Leu, and Asp, respectively), providing a rationale for the purine base specificity of S. venezuelae OtsA. To establish which donor is used in vivo, we generated an otsA null mutant in S. venezuelae. The mutant had a cell density-dependent growth phenotype and accumulated galactose 1-phosphate, glucose 1-phosphate, and GDP-glucose when grown on galactose. To determine how the GDP-glucose is generated, we characterized three candidate GDP-glucose pyrophosphorylases. SVEN_3027 is a UDP-glucose pyrophosphorylase, SVEN_3972 is an unusual ITP-mannose pyrophosphorylase, and SVEN_2781 is a pyrophosphorylase that is capable of generating GDP-glucose as well as GDP-mannose. We have therefore established how S. venezuelae can make and utilize GDP-glucose in the biosynthesis of trehalose 6-phosphate. PMID:27903647

  8. Waste cooking oil as substrate for biosynthesis of poly(3-hydroxybutyrate and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate: Turning waste into a value-added product

    Directory of Open Access Journals (Sweden)

    Yang, T. A.

    2013-01-01

    Full Text Available Aims: Improper disposal of domestic wastes, such as waste cooking oil (WCO, contributes to the deterioration of the environment and may lead to health problems. In this study, we evaluated the potential of plant-based WCO as a carbon source for the commercial biosynthesis of the bio-plastics, poly(3-hydroxybutyrate and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate. The consumption of WCO for this purpose would mitigate their pollution of the environment at the same time.Methodology and Results: WCO collected from several cafeterias in USM was tested as the carbon source for polyhydroxyalkanoates (PHA production. A selection of suitable nitrogen source was first conducted in order to obtain an acceptable number of dry cell weight (DCW and PHA content. Urea was found to be a suitable nitrogen source for the two bacterial strains used in our study, Cupriavidus necator H16 and its transformed mutant, C. necator PHB¯4 harboring the PHA synthase gene of Aeromonas caviae (PHB¯4/pBBREE32d13. With WCO as the sole carbon source, C. necator H16 yielded a relatively good dry cell weight (DCW=25.4 g/L, with 71 wt% poly(3-hydroxybutyrate P(3HBcontent. In comparison, the DCW obtained with fresh cooking oil (FCO was 24.8 g/L. The production of poly(3 hydroxybutyrate-co-3- hydroxyhexanoate [P(3HB-co-3HHx] from WCO by the transformant C. necator PHB¯4 was comparable, yielding a DCW of 22.3 g/L and P(3HB-co-3HHx content of 85 wt%. Lipase activities for both bacterial strains reached a maximum after 72 h of cultivation when time profile was conducted. Conclusion, significance and impact of study: The use of WCO as a carbon source in the biosynthesis of the bioplastic, PHA, turns a polluting domestic waste into a value-added biodegradable product. This renewable source material can thus be exploited for the low cost production of PHA.

  9. Green Extraction of Natural Products: Concept and Principles

    OpenAIRE

    Giancarlo Cravotto; Maryline Abert Vian; Farid Chemat

    2012-01-01

    The design of green and sustainable extraction methods of natural products is currently a hot research topic in the multidisciplinary area of applied chemistry, biology and technology. Herein we aimed to introduce the six principles of green-extraction, describing a multifaceted strategy to apply this concept at research and industrial level. The mainstay of this working protocol are new and innovative technologies, process intensification, agro-solvents and energy saving. The concept, princi...

  10. Natural Products Research in China From 2015 to 2016

    OpenAIRE

    Haishan Liu; Haishan Liu; Guoliang Zhu; Guoliang Zhu; Yaqin Fan; Yaqin Fan; Yuqi Du; Yuqi Du; Mengmeng Lan; Mengmeng Lan; Yibo Xu; Yibo Xu; Weiming Zhu; Weiming Zhu

    2018-01-01

    This review covers the literature published by chemists from China during the 2015–2016 on natural products (NPs), with 1,985 citations referring to 6,944 new compounds isolated from marine or terrestrial microorganisms, plants, and animals. The emphasis is on 730 new compounds with a novel skeleton or/and significant bioactivity, together with their source organism and country of origin.

  11. Natural Products for the Treatment of Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Ríos, José Luis; Francini, Flavio; Schinella, Guillermo R

    2015-08-01

    Type 2 diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia. High blood sugar can produce long-term complications such as cardiovascular and renal disorders, retinopathy, and poor blood flow. Its development can be prevented or delayed in people with impaired glucose tolerance by implementing lifestyle changes or the use of therapeutic agents. Some of these drugs have been obtained from plants or have a microbial origin, such as galegine isolated from Galega officinalis, which has a great similarity to the antidiabetic drug metformin. Picnogenol, acarbose, miglitol, and voglibose are other antidiabetic products of natural origin. This review compiles the principal articles on medicinal plants used for treating diabetes and its comorbidities, as well as mechanisms of natural products as antidiabetic agents. Inhibition of α-glucosidase and α-amylase, effects on glucose uptake and glucose transporters, modification of mechanisms mediated by the peroxisome proliferator-activated receptor, inhibition of protein tyrosine phosphatase 1B activity, modification of gene expression, and activities of hormones involved in glucose homeostasis such as adiponectin, resistin, and incretin, and reduction of oxidative stress are some of the mechanisms in which natural products are involved. We also review the most relevant clinical trials performed with medicinal plants and natural products such as aloe, banaba, bitter melon, caper, cinnamon, cocoa, coffee, fenugreek, garlic, guava, gymnema, nettle, sage, soybean, green and black tea, turmeric, walnut, and yerba mate. Compounds of high interest as potential antidiabetics are: fukugetin, palmatine, berberine, honokiol, amorfrutins, trigonelline, gymnemic acids, gurmarin, and phlorizin. Georg Thieme Verlag KG Stuttgart · New York.

  12. Cytotoxic Natural Products from Marine Sponge-Derived Microorganisms

    Directory of Open Access Journals (Sweden)

    Huawei Zhang

    2017-03-01

    Full Text Available A growing body of evidence indicates that marine sponge-derived microbes possess the potential ability to make prolific natural products with therapeutic effects. This review for the first time provides a comprehensive overview of new cytotoxic agents from these marine microbes over the last 62 years from 1955 to 2016, which are assorted into seven types: terpenes, alkaloids, peptides, aromatics, lactones, steroids, and miscellaneous compounds.

  13. Dietary Natural Products for Prevention and Treatment of Breast Cancer

    OpenAIRE

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-01-01

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi...

  14. Non-canonical regulation of glutathione and trehalose biosynthesis characterizes non-Saccharomyces wine yeasts with poor performance in active dry yeast production

    Directory of Open Access Journals (Sweden)

    Esther Gamero-Sandemetrio

    2018-01-01

    Full Text Available Several yeast species, belonging to Saccharomyces and non-Saccharomyces genera, play fundamental roles during spontaneous must grape fermentation, and recent studies have shown that mixed fermentations, co-inoculated with S. cerevisiae and non-Saccharomyces strains, can improve wine organoleptic properties. During active dry yeast (ADY production, antioxidant systems play an essential role in yeast survival and vitality as both biomass propagation and dehydration cause cellular oxidative stress and negatively affect technological performance. Mechanisms for adaptation and resistance to desiccation have been described for S. cerevisiae, but no data are available on the physiology and oxidative stress response of non-Saccharomyces wine yeasts and their potential impact on ADY production. In this study we analyzed the oxidative stress response in several non-Saccharomyces yeast species by measuring the activity of reactive oxygen species (ROS scavenging enzymes, e.g., catalase and glutathione reductase, accumulation of protective metabolites, e.g., trehalose and reduced glutathione (GSH, and lipid and protein oxidation levels. Our data suggest that non-canonical regulation of glutathione and trehalose biosynthesis could cause poor fermentative performance after ADY production, as it corroborates the corrective effect of antioxidant treatments, during biomass propagation, with both pure chemicals and food-grade argan oil.

  15. Rationale for a natural products approach to herbicide discovery.

    Science.gov (United States)

    Dayan, Franck E; Owens, Daniel K; Duke, Stephen O

    2012-04-01

    Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry. Published 2012 by John Wiley & Sons, Ltd.

  16. Automated genome mining of ribosomal peptide natural products

    Energy Technology Data Exchange (ETDEWEB)

    Mohimani, Hosein; Kersten, Roland; Liu, Wei; Wang, Mingxun; Purvine, Samuel O.; Wu, Si; Brewer, Heather M.; Pasa-Tolic, Ljiljana; Bandeira, Nuno; Moore, Bradley S.; Pevzner, Pavel A.; Dorrestein, Pieter C.

    2014-07-31

    Ribosomally synthesized and posttranslationally modified peptides (RiPPs), especially from microbial sources, are a large group of bioactive natural products that are a promising source of new (bio)chemistry and bioactivity (1). In light of exponentially increasing microbial genome databases and improved mass spectrometry (MS)-based metabolomic platforms, there is a need for computational tools that connect natural product genotypes predicted from microbial genome sequences with their corresponding chemotypes from metabolomic datasets. Here, we introduce RiPPquest, a tandem mass spectrometry database search tool for identification of microbial RiPPs and apply it for lanthipeptide discovery. RiPPquest uses genomics to limit search space to the vicinity of RiPP biosynthetic genes and proteomics to analyze extensive peptide modifications and compute p-values of peptide-spectrum matches (PSMs). We highlight RiPPquest by connection of multiple RiPPs from extracts of Streptomyces to their gene clusters and by the discovery of a new class III lanthipeptide, informatipeptin, from Streptomyces viridochromogenes DSM 40736 as the first natural product to be identified in an automated fashion by genome mining. The presented tool is available at cy-clo.ucsd.edu.

  17. Natural Radiation in byproducts of the production of phosphoric acid

    International Nuclear Information System (INIS)

    Silveira, Marcilei A. Guazzelli da; Cardoso, L.L.; Medina, N.H.

    2014-01-01

    Natural radiation is the largest source of radiation exposure to which man is subject. It is formed basically by cosmic radiation and the radionuclides present in the Earth crust, as 40 K and the elements of the decay series of 232 Th and 238 U. Phosphate ores, which constitutes the raw material for the production of phosphoric acid, have a high rate of natural radiation from the decay series of 232 Th and 238 U. Phosphogypsum, which is naturally radioactivity, is a by-product of the production of phosphoric acid by the wet method. For each ton of phosphoric acid it is produced about 4.5 tons of phosphogypsum. This work presents the analysis of samples collected in all stages of the manufacturing process of phosphoric acid, which generates the phosphogypsum. Gamma-ray spectrometry was used to measure the concentration of the elements of the decay series of 232 Th and 238 U. All analyzed samples showed a high concentration of radionuclides, promoting the need for further steps in the process in order to reduce the presence of such radionuclides in the phosphogypsum. The results indicate the radionuclide 238 U has higher contribution in some samples of the intermediate stages of the process. All samples exceeded the international average range of human exposure to terrestrial gamma radiation, which is 0.3 to 1.0 mSv/year. (author)

  18. Novel fermentation processes for manufacturing plant natural products.

    Science.gov (United States)

    Zhou, Jingwen; Du, Guocheng; Chen, Jian

    2014-02-01

    Microbial production of plant natural products (PNPs), such as terpenoids, flavonoids from renewable carbohydrate feedstocks offers sustainable and economically attractive alternatives to their petroleum-based production. Rapid development of metabolic engineering and synthetic biology of microorganisms shows many advantages to replace the current extraction of these useful high price chemicals from plants. Although few of them were actually applied on a large scale for PNPs production, continuous research on these high-price chemicals and the rapid growing global market of them, show the promising future for the production of these PNPs by microorganisms with a more economic and environmental friendly way. Introduction of novel pathways and optimization of the native cellular processes by metabolic engineering of microorganisms for PNPs production are rapidly expanding its range of cell-factory applications. Here we review recent progress in metabolic engineering of microorganisms for the production of PNPs. Besides, factors restricting the yield improvement and application of lab-scale achievements to industrial applications have also been discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Biosynthesis of Tropolones in Streptomyces spp: Interweaving Biosynthesis and Degradation of Phenylacetic Acid and Hydroxylations on Tropone Ring.

    Science.gov (United States)

    Chen, Xuefei; Xu, Min; Lü, Jin; Xu, Jianguo; Wang, Yemin; Lin, Shuangjun; Deng, Zixin; Tao, Meifeng

    2018-04-13

    Tropolonoids are important natural products that contain a unique seven-membered aromatic tropolone core and exhibit remarkable biological activities. 3,7-Dihydroxytropolone (DHT) isolated from Streptomyces species is a multiply hydroxylated tropolone exhibiting antimicrobial, anticancer, and antiviral activities. Herein, we determined the DHT biosynthetic pathway by heterologous expression, gene deletion, and bioconversion. Nine trl genes and some of the aerobic phenylacetic acid degradation pathway genes ( paa ) located outside of the trl biosynthetic gene cluster are required for the heterologous production of DHT. The trlA gene encodes a single-domain protein homologous to the C-terminal enoyl-CoA hydratase domain of PaaZ. TrlA truncates the phenylacetic acid catabolic pathway and redirects it towards the formation of heptacyclic intermediates. TrlB is a 3-deoxy-D-arabino-heptulosonic acid-7-phosphate (DAHP) synthase homolog. TrlH is an unusual bifunctional protein bearing an N-terminal prephenate dehydratase domain and a C-terminal chorismate mutase domain. TrlB and TrlH enhanced de novo biosynthesis of phenylpyruvate, thereby providing abundant precursor for the prolific production of DHT in Streptomyces Six seven-membered carbocyclic compounds were identified from the gene deletion mutants of trlC , trlD , trlE , and trlF Four of these chemicals, including 1,4,6-cycloheptatriene-1-carboxylic acid, tropone, tropolone and 7-hydroxytropolone, were verified as key biosynthetic intermediates. TrlF is required for the conversion of 1,4,6-cycloheptatriene-1-carboxylic acid into tropone. Monooxygenases TrlE and TrlCD catalyze the regioselective hydroxylations of tropone to afford DHT. This study reveals a natural association of anabolism of chorismate and phenylpyruvate, catabolism of phenylacetic acid, and biosynthesis of tropolones in Streptomyces spp. IMPORTANCE Tropolonoids are promising drug lead compounds because of their versatile bioactivities attributed to

  20. Marine natural products in prevention and treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Zahra Ghanbari

    2015-05-01

    Full Text Available Undoubtedly, pharmaceutical and nutritional factors play an important role in the prevention of age-related bone loss. According to the several studies so far, the effects of nutrients and bioactive components which are extracted from marine resources are very promising in osteoporosis. Most of these investigations have been done on various marine algae extracts. Since, algae are rich source of essential minerals, primary and secondary unique natural products, several amino acids and growth factors their extracts show favorable effects on bone metabolism. Moreover, it has been shown that marine nutrients such as marine fishes, shrimp and crabs increase the absorption of calcium and bone collagen synthesis or reduce the production of prostaglandins and decrease the deoxypyridinoline disposal. On the other hand, secondary products which are extracted and characterized from marine organisms such as mollusks, fungi, bacteria, sponges and coral reefs show anti-osteoporosis activities via the inhibition of osteoclast differentiation and the induction of apoptosis in osteoclasts like cells or stimulation of osteoblast differentiation. Although, several investigations have been done in this area, many of studies have been carried out on animal models, like ovariectomy-induced bone loss in mice. Hence, clinical investigations are warranted to develop marine natural products against bone loss and to prevent osteoporosis.

  1. The water-food nexus of natural rubber production

    Science.gov (United States)

    Chiarelli, D. D.; Rosa, L.; Rulli, M. C.; D'Odorico, P.

    2017-12-01

    The increasing global demand for natural rubber (100% increase in the last 15 years) is for most part met by Malaysia and Indonesia, and - to a lesser extent - other countries in south-east Asia and Africa. The consequent expansion of rubber plantation has often occurred at the expenses of agricultural land for staple food, particularly in southeast Asia, where most of the land suitable for agriculture is already harvested for food crops or other uses. Here we investigate the extent to which the ongoing increase in rubber production is competing with the food system and affecting the livelihoods of rural communities in the areas of production and their appropriation of natural resources, such as water. We also investigate to what extent the expansion of rubber plantations is taking place through large scale land acquisitions (LSLAs) and evaluate the impacts on rural communities. Our results show how rubber production has strong environmental, social and economic impacts. Despite their ability to bring employment and increase the average income of economically disadvantaged areas, rubber plantations may threaten the local water and food security and induce a loss of rural livelihoods, particularly when the new plantations result from LSLAs that displace semi-subsistence forms of production thereby forcing the local populations to depend on global markets.

  2. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

    Science.gov (United States)

    Rayan, Anwar; Raiyn, Jamal; Falah, Mizied

    2017-01-01

    Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

  3. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

    Directory of Open Access Journals (Sweden)

    Anwar Rayan

    Full Text Available Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

  4. Natural products as potential cancer therapy enhancers: A preclinical update

    Directory of Open Access Journals (Sweden)

    Abed Agbarya

    2014-09-01

    Full Text Available Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  5. Production of hydrogen by thermocatalytic cracking of natural gas

    Energy Technology Data Exchange (ETDEWEB)

    Muradov, N. [Florida Solar Energy Center, Cocoa, FL (United States)

    1996-10-01

    The conventional methods of hydrogen production from natural gas (for example, steam reforming and partial oxidation) are complex, multi-step processes that produce large quantities of CO{sub 2}. The main goal of this project is to develop a technologically simple process for hydrogen production from natural gas (NG) and other hydrocarbon fuels via single-step decomposition of hydrocarbons. This approach eliminates or significantly reduces CO{sub 2} emission. Carbon is a valuable by-product of this process, whereas conventional methods of hydrogen production from NG produce no useful by-products. This approach is based on the use of special catalysts that reduce the maximum temperature of the process from 1400-1500{degrees}C (thermal non-catalytic decomposition of methane) to 500-900{degrees}C. Transition metal based catalysts and various forms of carbon are among the candidate catalysts for the process. This approach can advantageously be used for the development of compact NG reformers for on-site production of hydrogen-methane blends at refueling stations and, also, for the production of hydrogen-rich gas for fuel cell applications. The author extended the search for active methane decomposition catalysts to various modifications of Ni-, Fe-, Mo- and Co-based catalysts. Variation in the operational parameters makes it possible to produce H{sub 2}-CH{sub 4} blends with a wide range of hydrogen concentrations that vary from 15 to 98% by volume. The author found that Ni-based catalysts are more effective at temperatures below 750{degrees}C, whereas Fe-based catalysts are effective at temperatures above 800{degrees}C for the production of hydrogen with purity of 95% v. or higher. The catalytic pyrolysis of liquid hydrocarbons (pentane, gasoline) over Fe-based catalyst was conducted. The author observed the production of a hydrogen-rich gas (hydrogen concentration up to 97% by volume) at a rate of approximately 1L/min.mL of hydrocarbon fuel.

  6. Biosynthesis of Anthocyanins and Their Regulation in Colored Grapes

    Directory of Open Access Journals (Sweden)

    Guo-Liang Yan

    2010-12-01

    Full Text Available Anthocyanins, synthesized via the flavonoid pathway, are a class of crucial phenolic compounds which are fundamentally responsible for the red color of grapes and wines. As the most important natural colorants in grapes and their products, anthocyanins are also widely studied for their numerous beneficial effects on human health. In recent years, the biosynthetic pathway of anthocyanins in grapes has been thoroughly investigated. Their intracellular transportation and accumulation have also been further clarified. Additionally, the genetic mechanism regulating their biosynthesis and the phytohormone influences on them are better understood. Furthermore, due to their importance in the quality of wine grapes, the effects of the environmental factors and viticulture practices on anthocyanin accumulation are being investigated increasingly. The present paper summarizes both the basic information and the most recent advances in the study of the anthocyanin biosynthesis in red grapes, emphasizing their gene structure, the transcriptional factors and the diverse exterior regulation factors.

  7. Biosynthesis of anthocyanins and their regulation in colored grapes.

    Science.gov (United States)

    He, Fei; Mu, Lin; Yan, Guo-Liang; Liang, Na-Na; Pan, Qiu-Hong; Wang, Jun; Reeves, Malcolm J; Duan, Chang-Qing

    2010-12-09

    Anthocyanins, synthesized via the flavonoid pathway, are a class of crucial phenolic compounds which are fundamentally responsible for the red color of grapes and wines. As the most important natural colorants in grapes and their products, anthocyanins are also widely studied for their numerous beneficial effects on human health. In recent years, the biosynthetic pathway of anthocyanins in grapes has been thoroughly investigated. Their intracellular transportation and accumulation have also been further clarified. Additionally, the genetic mechanism regulating their biosynthesis and the phytohormone influences on them are better understood. Furthermore, due to their importance in the quality of wine grapes, the effects of the environmental factors and viticulture practices on anthocyanin accumulation are being investigated increasingly. The present paper summarizes both the basic information and the most recent advances in the study of the anthocyanin biosynthesis in red grapes, emphasizing their gene structure, the transcriptional factors and the diverse exterior regulation factors.

  8. Enhanced production of natural yellow pigments from Monascus purpureus by liquid culture: The relationship between fermentation conditions and mycelial morphology.

    Science.gov (United States)

    Lv, Jun; Zhang, Bo-Bo; Liu, Xiao-Dong; Zhang, Chan; Chen, Lei; Xu, Gan-Rong; Cheung, Peter Chi Keung

    2017-10-01

    Natural yellow pigments produced by submerged fermentation of Monascus purpureus have potential economic value and application in the food industry. In the present study, the relationships among fermentation conditions (in terms of pH and shaking/agitation speed), mycelial morphology and the production of Monascus yellow pigments were investigated in both shake-flask and scale-up bioreactor experiments. In the shake-flask fermentation, the highest yield of the Monascus yellow pigments was obtained at pH 5.0 and a shaking speed of 180 rpm. Microscopic images revealed that these results were associated with the formation of freely dispersed small mycelial pellets with shorter, thicker and multi-branched hyphae. Further investigation indicated that the hyphal diameter was highly correlated with the biosynthesis of the Monascus yellow pigments. In a scaled-up fermentation experiment, the yield of yellow pigments (401 U) was obtained in a 200-L bioreactor, which is the highest yield to the best of our knowledge. The present findings can advance our knowledge on the conditions used for enhancing the production of Monascus yellow pigments in submerged fermentation and facilitate large-scale production of these natural pigments. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  9. [Advances in metabolic engineering for the microbial production of naturally occurring terpenes-limonene and bisabolene: a mini review].

    Science.gov (United States)

    Pang, Yaru; Hu, Zhihui; Xiao, Dongguang; Yu, Aiqun

    2018-01-25

    Limonene (C₁₀H₁₆) and bisabolene (C₁₅H₂₄) are both naturally occurring terpenes in plants. Depending on the number of C₅ units, limonene and bisabolene are recognized as representative monoterpenes and sesquiterpenes, respectively. Limonene and bisabolene are important pharmaceutical and nutraceutical products used in the prevention and treatment of cancer and many other diseases. In addition, they can be used as starting materials to produce a range of commercially valuable products, such as pharmaceuticals, nutraceuticals, cosmetics, and biofuels. The low abundance or yield of limonene and bisabolene in plants renders their isolation from plant sources non-economically viable. Isolation of limonene and bisabolene from plants also suffers from low efficiency and often requires harsh reaction conditions, prolonged reaction times, and expensive equipment cost. Recently, the rapid developments in metabolic engineering of microbes provide a promising alternative route for producing these plant natural products. Therefore, producing limonene and bisabolene by engineering microbial cells into microbial factories is becoming an attractive alternative approach that can overcome the bottlenecks, making it more sustainable, environmentally friendly and economically competitive. Here, we reviewed the status of metabolic engineering of microbes that produce limonene and bisabolene including microbial hosts, key enzymes, metabolic pathways and engineering of limonene/bisabolene biosynthesis. Furthermore, key challenges and future perspectives were discussed.

  10. Liquefied natural gas (LNG) : production, storage and handling. 7. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Kalra, S; Jaron, K; Adragna, M; Coyle, S; Foley, C; Hawryn, S; Martin, A; McConnell, J [eds.

    2003-07-01

    This Canadian Standard on the production, storage and handling of liquefied natural gas (LNG) was prepared by the Technical Committee on Liquefied Natural Gas under the jurisdiction of the Steering Committee on Oil and Gas Industry Systems and Materials. It establishes the necessary requirements for the design, installation and safe operation of LNG facilities. The Standard applies to the design, location, construction, operation and maintenance of facilities at any location of the liquefaction of natural gas and for the storage, vaporization, transfer, handling and truck transport of LNG. The training of personnel involved is also included as well as containers for LNG storage, including insulated vacuum systems. It includes non-mandatory guidelines for small LNG facilities but does not apply to the transportation of refrigerants, LNG by rail, marine vessel or pipeline. This latest edition contains changes in working of seismic design requirements and minor editorial changes to several clauses to bring the Standard closer to the US National Fire Protection Association's Committee on Liquefied Natural Gas Standard while maintaining Canadian regulatory requirements. The document is divided into 12 sections including: general requirements; plant site provisions; process equipment; stationary LNG storage containers; vaporization facilities; piping system and components; instrumentation and electrical services; transfer of LNG and refrigerants; fire protection, safety and security; and, operating, maintenance and personnel training. This Standard, like all Canadian Standards, was subject to periodic review and was most recently reaffirmed in 2003. 6 tabs., 6 figs., 3 apps.

  11. Production of bio-synthetic natural gas in Canada.

    Science.gov (United States)

    Hacatoglu, Kevork; McLellan, P James; Layzell, David B

    2010-03-15

    Large-scale production of renewable synthetic natural gas from biomass (bioSNG) in Canada was assessed for its ability to mitigate energy security and climate change risks. The land area within 100 km of Canada's network of natural gas pipelines was estimated to be capable of producing 67-210 Mt of dry lignocellulosic biomass per year with minimal adverse impacts on food and fiber production. Biomass gasification and subsequent methanation and upgrading were estimated to yield 16,000-61,000 Mm(3) of pipeline-quality gas (equivalent to 16-63% of Canada's current gas use). Life-cycle greenhouse gas emissions of bioSNG-based electricity were calculated to be only 8.2-10% of the emissions from coal-fired power. Although predicted production costs ($17-21 GJ(-1)) were much higher than current energy prices, a value for low-carbon energy would narrow the price differential. A bioSNG sector could infuse Canada's rural economy with $41-130 billion of investments and create 410,000-1,300,000 jobs while developing a nation-wide low-carbon energy system.

  12. Natural Gas Reserves, Development and Production in Qatar

    International Nuclear Information System (INIS)

    Naji, Abi-Aad.

    1998-01-01

    Qatar entered the club of natural gas exporters in early 1997 when the first shipment of liquefied natural gas left the state for Japan. Qatar was helped by the discovery in 1971 of supergiant North Field gas field, the country's suitable location between the established gas consuming markets in Europe and Southeast Asia, and its proximity to developing markets in the Indian subcontinent and in neighbouring countries. All that have combined to make gas export projects from Qatar economically viable and commercially attractive. In addition to export-oriented development, increased gas production from the North Field is planned for meeting a growing domestic demand for gas as fuel and feedstock for power generation and desalination plants, as well as value-added petrochemical and fertilizer industries

  13. Bridging the gap: basic metabolomics methods for natural product chemistry.

    Science.gov (United States)

    Jones, Oliver A H; Hügel, Helmut M

    2013-01-01

    Natural products and their derivatives often have potent physiological activities and therefore play important roles as both frontline treatments for many diseases and as the inspiration for chemically synthesized therapeutics. However, the detection and synthesis of new therapeutic compounds derived from, or inspired by natural compounds has declined in recent years due to the increased difficulty of identifying and isolating novel active compounds. A new strategy is therefore necessary to jumpstart this field of research. Metabolomics, including both targeted and global metabolite profiling strategies, has the potential to be instrumental in this effort since it allows a systematic study of complex mixtures (such as plant extracts) without the need for prior isolation of active ingredients (or mixtures thereof). Here we describe the basic steps for conducting metabolomics experiments and analyzing the results using some of the more commonly used analytical and statistical methodologies.

  14. Conceptual process synthesis for recovery of natural products from plants

    DEFF Research Database (Denmark)

    Malwade, Chandrakant R.; Qu, Haiyan; Rong, Ben-Guang

    2013-01-01

    ) and purification of target compound(s) from the crude extract. Process analytical technology (PAT) is used in each step to understand the nature of material systems and separation characteristics of each separation method. In the present work, this methodology is applied to generate process flow sheet for recovery......A systematic method of conceptual process synthesis for recovery of natural products from their biological sources is presented. This methodology divides the task into two major subtasks namely, isolation of target compound from a chemically complex solid matrix of biological source (crude extract...... in individual unit operations of maceration, flash column chromatography, and crystallization are 90.0%, 87.1, and 47.6%, respectively. Results showed that the crystallization step is dominant to the overall yield of the process which was 37.3%....

  15. Water for wood products versus nature, food or feed

    Science.gov (United States)

    Schyns, Joep; Booij, Martijn; Hoekstra, Arjen

    2017-04-01

    more water available for the generation of other ecosystem services. Our findings contribute to a more complete picture of the human appropriation of water and the understanding of the interlinkages between the SDGs, thus feeding the debate on water for wood products versus nature, food or feed.

  16. A general enantioselective route to the chamigrene natural product family

    KAUST Repository

    White, David E.

    2010-06-01

    Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.

  17. Bioactive Natural Products of Marine Sponges from the Genus Hyrtios

    Directory of Open Access Journals (Sweden)

    Nourhan Hisham Shady

    2017-05-01

    Full Text Available Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.

  18. Green extraction of natural products: concept and principles.

    Science.gov (United States)

    Chemat, Farid; Vian, Maryline Abert; Cravotto, Giancarlo

    2012-01-01

    The design of green and sustainable extraction methods of natural products is currently a hot research topic in the multidisciplinary area of applied chemistry, biology and technology. Herein we aimed to introduce the six principles of green-extraction, describing a multifaceted strategy to apply this concept at research and industrial level. The mainstay of this working protocol are new and innovative technologies, process intensification, agro-solvents and energy saving. The concept, principles and examples of green extraction here discussed, offer an updated glimpse of the huge technological effort that is being made and the diverse applications that are being developed.

  19. Natural product diversity of actinobacteria in the Atacama Desert.

    Science.gov (United States)

    Rateb, Mostafa E; Ebel, Rainer; Jaspars, Marcel

    2018-02-14

    The Atacama Desert of northern Chile is considered one of the most arid and extreme environment on Earth. Its core region was described as featuring "Mars-like" soils that were at one point deemed too extreme for life to exist. However, recent investigations confirmed the presence of diverse culturable actinobacteria. In the current review, we discuss a total of 46 natural products isolated to date representing diverse chemical classes characterized from different actinobacteria isolated from various locations in the Atacama Desert. Their reported biological activities are also discussed.

  20. Enantiospecific Synthesis of Trisubstituted Butyrolactone Natural Products and Their Analogs.

    Science.gov (United States)

    Sibi, Mukund P.; Lu, Jianliang; Talbacka, Chelsy L.

    1996-11-01

    A general methodology for the synthesis of highly substituted butyrolactones in enantiomerically pure form has been developed. The application of this process in a highly efficient synthesis of lactone natural products blastmycinone (1), NFX-2 (2), antimycinone (3), and NFX-4 (4) and two lipid metabolites (5, 6) are described. Additionally, the total synthesis of 5-epi-blastmycinone (22), 5-epi-NFX-2 (21b), 5-epi-NFX-4 (21c), and lipid metabolite analogs (19, 20) are also described. The overall yields for the target molecules are the highest reported so far in the literature.

  1. A general enantioselective route to the chamigrene natural product family

    KAUST Repository

    White, David E.; Stewart, Ian C.; Seashore-Ludlow, Brinton A.; Grubbs, Robert H.; Stoltz, Brian M.

    2010-01-01

    Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.

  2. Marine Vibrionaceae as a source of bioactive natural products

    DEFF Research Database (Denmark)

    Månsson, Maria; Wietz, Matthias; Gram, Lone

    an ecological function. Using chemical profiling, vibrio strains were compared on a global scale, revealing that the production of certain compounds is a conserved feature independent of sample locations. Chemical screening techniques such as explorative solid-phase extraction led to the isolation of two novel...... that some strains were capable of producing antibacterial compounds when grown on natural substrates such as chitin or seaweed. One Vibrio coralliilyticus strain was capable of producing the antibacterial compound when using chitin as the sole carbon source and in a live chitin model system, suggesting...... of which possess biological activities attractive for alternative strategies in antibacterial therapy....

  3. Natural product antifoulants from the octocorals of Indian waters

    Digital Repository Service at National Institute of Oceanography (India)

    Raveendran, T.V.; LimnaMol, V.P.; Parameswaran, P.S.

    stream_size 22497 stream_content_type text/plain stream_name Int_Biodeterior_Biodegrad_65_265a.pdf.txt stream_source_info Int_Biodeterior_Biodegrad_65_265a.pdf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8... 1 Author version: International Biodeterioration & Biodegradation, vol.65(1); 2011; 265-268 Natural Product Antifoulants from the Octocorals of Indian waters T.V. Raveendran * , V.P. Limna Mol, P.S. Parameswaran National Institute...

  4. Green Extraction of Natural Products: Concept and Principles

    Directory of Open Access Journals (Sweden)

    Giancarlo Cravotto

    2012-07-01

    Full Text Available The design of green and sustainable extraction methods of natural products is currently a hot research topic in the multidisciplinary area of applied chemistry, biology and technology. Herein we aimed to introduce the six principles of green-extraction, describing a multifaceted strategy to apply this concept at research and industrial level. The mainstay of this working protocol are new and innovative technologies, process intensification, agro-solvents and energy saving. The concept, principles and examples of green extraction here discussed, offer an updated glimpse of the huge technological effort that is being made and the diverse applications that are being developed.

  5. The Canadian Natural Health Products (NHP) regulations: industry compliance motivations.

    Science.gov (United States)

    Laeeque, Hina; Boon, Heather; Kachan, Natasha; Cohen, Jillian Clare; D'Cruz, Joseph

    2007-06-01

    This qualitative study explores corporations' motivations to comply with new natural health products (NHP) Regulations in Canada. Interviews were conducted with representatives from 20 Canadian NHP companies. Findings show that the rationale for compliance differs for large compared to small and medium-sized enterprises (SMEs). Large firms are motivated to comply with the regulations because of the deterrent fear of negative media coverage, social motivations, ability to comply and maintaining a competitive market advantage. In contrast, SMEs are motivated to comply due to the deterrent fear of legal prosecution and a sense of duty.

  6. Geochemistry of actinides and fission products in natural aquifer systems

    International Nuclear Information System (INIS)

    Kim, J.I.

    1989-06-01

    The progress in the research area of the community project MIRAGE: 'Geochemistry of actinides and fission products in natural aquatic systems' has been reviewed. This programme belongs to a specific research and technical development programme for the European Atomic Energy Community in the field of management and storage of radioactive waste. The review summarizes research progresses in subject areas: complexation with organics, colloid generation in groundwater and basic retention mechanisms in the framework of the migration of radionuclides in the geosphere. The subject areas are being investigated by 23 laboratories under interlaboratory collaborations or independent studies. (orig.)

  7. Environmental review of natural gas production in Lake Erie

    International Nuclear Information System (INIS)

    O'Shea, K.

    2002-01-01

    The water of Lake Erie is used as a source of drinking water for Ontario, New York, Pennsylvania, Ohio and Michigan. An environmental review has been conducted to determine the impact of drilling operations on the overall ecology of the lake. Since 1913, 2000 natural gas wells have been drilled in Lake Erie, of which 550 currently produce gas and account for 75 per cent of Ontario's total gas production. 180 wells are shut-in or suspended and the remaining wells have been abandoned. The gas wells are connected to onshore production facilities by approximately 1,600 km of small diameter pipelines that lie buried near shore or on top of the lake bed. Nearly 90 per cent of the in-lake infrastructure is in water depths of more than 20 metres. Talisman Energy is actively involved with the Canadian Coast Guard, the Department of Fisheries and Oceans, and the Ministry of Natural Resources to ensure cooperation between regulators and off-shore personnel. The environmental assessment of natural gas production in Lake Erie included a review of regulatory and best management practices, a biophysical overview of the lake, and a review of drilling practices, well completions, handling of waste streams, materials management, operations inspections, wastewater discharge, air emissions, and oil spills. It was revealed that for most drilling programs, cuttings are washed and discharged to the Lake. Ongoing testing will determine the impact that this practice has on benthic populations. The drill muds used for drilling operations are water based, environmentally friendly, and re-used between well locations. For completion programs, all well activities are closed circuit operations. Wells are abandoned through plugging with cement, removing wellheads and casing below the lake bottom. There has been a reported volume of about 23,000 litres of spilled product from 1990 to 2001, of which 68 per cent has come from 3 industrial companies that operate near Lake Erie. The offshore gas

  8. A Molecular Description of Cellulose Biosynthesis

    Science.gov (United States)

    McNamara, Joshua T.; Morgan, Jacob L.W.; Zimmer, Jochen

    2016-01-01

    Cellulose is the most abundant biopolymer on Earth, and certain organisms from bacteria to plants and animals synthesize cellulose as an extracellular polymer for various biological functions. Humans have used cellulose for millennia as a material and an energy source, and the advent of a lignocellulosic fuel industry will elevate it to the primary carbon source for the burgeoning renewable energy sector. Despite the biological and societal importance of cellulose, the molecular mechanism by which it is synthesized is now only beginning to emerge. On the basis of recent advances in structural and molecular biology on bacterial cellulose synthases, we review emerging concepts of how the enzymes polymerize glucose molecules, how the nascent polymer is transported across the plasma membrane, and how bacterial cellulose biosynthesis is regulated during biofilm formation. Additionally, we review evolutionary commonalities and differences between cellulose synthases that modulate the nature of the cellulose product formed. PMID:26034894

  9. Personal-Care Products Formulated with Natural Antioxidant Extracts

    Directory of Open Access Journals (Sweden)

    Maria Luisa Soto

    2018-01-01

    Full Text Available The objective of this study was to evaluate the potential use of some vegetal raw materials in personal-care products. Four ethanolic extracts (grape pomace, Pinus pinaster wood chips, Acacia dealbata flowers, and Lentinus edodes were prepared and total phenolics, monomeric sugars, and antioxidant capacity were determined on alcoholic extracts. Six of the most important groups of cosmetics products (hand cream, body oil, shampoo, clay mask, body exfoliating cream, and skin cleanser were formulated. Participants evaluated some sensory attributes and overall acceptance by a 10-point scale; the results showed differences among age-intervals, but not between males and females. The results confirmed that all extracts presented characteristics appropriate for their use in cosmetic formulations and their good acceptability by consumers into all cosmetic products. Texture/appearance, spreadability, and skin feeling are important attributes among consumer expectations, but odor and color were the primary drivers and helped differentiate the natural extracts added into all personal-care products.

  10. US production of natural gas from tight reservoirs

    International Nuclear Information System (INIS)

    1993-01-01

    For the purposes of this report, tight gas reservoirs are defined as those that meet the Federal Energy Regulatory Commission's (FERC) definition of tight. They are generally characterized by an average reservoir rock permeability to gas of 0.1 millidarcy or less and, absent artificial stimulation of production, by production rates that do not exceed 5 barrels of oil per day and certain specified daily volumes of gas which increase with the depth of the reservoir. All of the statistics presented in this report pertain to wells that have been classified, from 1978 through 1991, as tight according to the FERC; i.e., they are ''legally tight'' reservoirs. Additional production from ''geologically tight'' reservoirs that have not been classified tight according to the FERC rules has been excluded. This category includes all producing wells drilled into legally designated tight gas reservoirs prior to 1978 and all producing wells drilled into physically tight gas reservoirs that have not been designated legally tight. Therefore, all gas production referenced herein is eligible for the Section 29 tax credit. Although the qualification period for the credit expired at the end of 1992, wells that were spudded (began to be drilled) between 1978 and May 1988, and from November 5, 1990, through year end 1992, are eligible for the tax credit for a subsequent period of 10 years. This report updates the EIA's tight gas production information through 1991 and considers further the history and effect on tight gas production of the Federal Government's regulatory and tax policy actions. It also provides some high points of the geologic background needed to understand the nature and location of low-permeability reservoirs

  11. Telomerase Inhibitors from Natural Products and Their Anticancer Potential

    Directory of Open Access Journals (Sweden)

    Kumar Ganesan

    2017-12-01

    Full Text Available Telomeres and telomerase are nowadays exploring traits on targets for anticancer therapy. Telomerase is a unique reverse transcriptase enzyme, considered as a primary factor in almost all cancer cells, which is mainly responsible to regulate the telomere length. Hence, telomerase ensures the indefinite cell proliferation during malignancy—a hallmark of cancer—and this distinctive feature has provided telomerase as the preferred target for drug development in cancer therapy. Deactivation of telomerase and telomere destabilization by natural products provides an opening to succeed new targets for cancer therapy. This review aims to provide a fundamental knowledge for research on telomere, working regulation of telomerase and its various binding proteins to inhibit the telomere/telomerase complex. In addition, the review summarizes the inhibitors of the enzyme catalytic subunit and RNA component, natural products that target telomeres, and suppression of transcriptional and post-transcriptional levels. This extensive understanding of telomerase biology will provide indispensable information for enhancing the efficiency of rational anti-cancer drug design.

  12. Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

    Directory of Open Access Journals (Sweden)

    Gaetan eMaertens

    2015-01-01

    Full Text Available We present a review of natural product syntheses accomplished in our laboratory during the last five years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the aromatic ring umpolung concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol, a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor, acetylaspidoalbidine (an antitumor agent, fortucine (antiviral and antitumor, erysotramidine (curare-like effect, platensimycin (an antibiotic, and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis. These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

  13. A diversity oriented synthesis of natural product inspired molecular libraries.

    Science.gov (United States)

    Chauhan, Jyoti; Luthra, Tania; Gundla, Rambabu; Ferraro, Antonio; Holzgrabe, Ulrike; Sen, Subhabrata

    2017-11-07

    Natural products are the source of innumerable pharmaceutical drug candidates and also form an important aspect of herbal remedies. They are also a source of various bioactive compounds. Herein we have leveraged the structural attributes of several natural products in building a library of architecturally diverse chiral molecules by harnessing R-tryptophan as the chiral auxiliary. It is converted to its corresponding methyl ester 1 which in turn provided a bevy of 1-aryl-tetrahydro-β-carbolines 2a-d, which were then converted to chiral compounds via a diversity oriented synthetic strategy (DOS). In general, intermolecular and intramolecular ring rearrangements facilitated the formation of the final compounds. Four different classes of molecules with distinct architectures were generated, adding up to nearly twenty-two individual molecules. Phenotypic screening of a representative section of the library revealed two molecules that selectively inhibit MCF7 breast cancer cells with IC 50 of ∼5 μg mL -1 potency.

  14. Applications of natural zeolites on agriculture and food production.

    Science.gov (United States)

    Eroglu, Nazife; Emekci, Mevlut; Athanassiou, Christos G

    2017-08-01

    Zeolites are crystalline hydrated aluminosilicates with remarkable physical and chemical properties, which include losing and receiving water in a reverse way, adsorbing molecules that act as molecular sieves, and replacing their constituent cations without structural change. The commercial production of natural zeolites has accelerated during the last 50 years. The Structure Commission of the International Zeolite Association recorded more than 200 zeolites, which currently include more than 40 naturally occurring zeolites. Recent findings have supported their role in stored-pest management as inert dust applications, pesticide and fertilizer carriers, soil amendments, animal feed additives, mycotoxin binders and food packaging materials. There are many advantages of inert dust application, including low cost, non-neurotoxic action, low mammalian toxicity and safety for human consumption. The latest consumer trends and government protocols have shifted toward organic origin materials to replace synthetic chemical products. In the present review, we summarize most of the main uses of zeolites in food and agruculture, along with the with specific paradigms that illustrate their important role. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  15. The potential of natural products for targeting PPARα

    Directory of Open Access Journals (Sweden)

    Daniela Rigano

    2017-07-01

    Full Text Available Peroxisome proliferator activated receptors (PPARs α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this “hot” target.

  16. Experience curve for natural gas production by hydraulic fracturing

    International Nuclear Information System (INIS)

    Fukui, Rokuhei; Greenfield, Carl; Pogue, Katie; Zwaan, Bob van der

    2017-01-01

    From 2007 to 2012 shale gas production in the US expanded at an astounding average growth rate of over 50%/yr, and thereby increased nearly tenfold over this short time period alone. Hydraulic fracturing technology, or “fracking”, as well as new directional drilling techniques, played key roles in this shale gas revolution, by allowing for extraction of natural gas from previously unviable shale resources. Although hydraulic fracturing technology had been around for decades, it only recently became commercially attractive for large-scale implementation. As the production of shale gas rapidly increased in the US over the past decade, the wellhead price of natural gas dropped substantially. In this paper we express the relationship between wellhead price and cumulative natural gas output in terms of an experience curve, and obtain a learning rate of 13% for the industry using hydraulic fracturing technology. This learning rate represents a measure for the know-how and skills accumulated thus far by the US shale gas industry. The use of experience curves for renewable energy options such as solar and wind power has allowed analysts, practitioners, and policy makers to assess potential price reductions, and underlying cost decreases, for these technologies in the future. The reasons for price reductions of hydraulic fracturing are fundamentally different from those behind renewable energy technologies – hence they cannot be directly compared – and hydraulic fracturing may soon reach, or maybe has already attained, a lower bound for further price reductions, for instance as a result of its water requirements or environmental footprint. Yet, understanding learning-by-doing phenomena as expressed by an industry-wide experience curve for shale gas production can be useful for strategic planning in the gas sector, as well as assist environmental policy design, and serve more broadly as input for projections of energy system developments. - Highlights: • Hydraulic

  17. Natural radioactivity product from coal burning in PLTU Pacitan

    International Nuclear Information System (INIS)

    Sukirno; Sri Murniasih; Rosidi; Sutanto WW

    2016-01-01

    Monitoring of radioactivity in the coal-fired power plant has been carried out in the CAST-NAA laboratory at 2015. Monitoring includes analysis of soil, water, fly ash, bottom ash and coal. The basic purpose of this work is the investigation of natural radionuclide contents in coal and the actual product samples in the Pacitan power plant as a first step to estimate the radioactive in the vicinity. This paper presents the results of the analysis of radioactivity in samples of coal, fly ash and bottom ash as well as environment samples of soil and water. Ra-226, Th-232, K-40, U-235, U-238, and Pb-210 Natural radionuclides are determined by gamma spectrometry with HPGe detector. Natural radionuclide in fine grain coal, bottom ash and fly ash have concentrations range (162.182 to 0.057) Bq/kg. Radioactivity contained in soil ranges (0.041 to 169.34) Bq/kg, whereas in water ranges (0.003 to 0.045) Bq/L. According Perka BAPETEN. No. 7 of 2013. On Boundary Value Environmental Radioactivity, the results of measurement analysis contained water around the power plant Pacitan still below the limit values allowed by BAPETEN. (author)

  18. Production of novel antioxidative phenolic amides through heterologous expression of the plant’s chlorogenic acid biosynthesis genes in yeast

    NARCIS (Netherlands)

    Moglia, A.; Comino, C.; Lanteri, S.; Vos, de C.H.; Waard, de P.; Beek, van T.A.; Goitre, L.; Retta, S.F.; Beekwilder, M.J.

    2010-01-01

    Phenolic esters like chlorogenic acid play an important role in therapeutic properties of many plant extracts. We aimed to produce phenolic esters in baker’s yeast, by expressing tobacco 4CL and globe artichoke HCT. Indeed yeast produced phenolic esters. However, the primary product was identified

  19. Lichen Symbiosis: Nature's High Yielding Machines for Induced Hydrogen Production

    Science.gov (United States)

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont’s and photobiont’s consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont’s hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications. PMID:25826211

  20. Lichen symbiosis: nature's high yielding machines for induced hydrogen production.

    Directory of Open Access Journals (Sweden)

    Aikaterini Papazi

    Full Text Available Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939 and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont's and photobiont's consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration establishes the required anoxic conditions for the activation of the phycobiont's hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications.

  1. MRE: a web tool to suggest foreign enzymes for the biosynthesis pathway design with competing endogenous reactions in mind

    KAUST Repository

    Kuwahara, Hiroyuki; Alazmi, Meshari; Cui, Xuefeng; Gao, Xin

    2016-01-01

    To rationally design a productive heterologous biosynthesis system, it is essential to consider the suitability of foreign reactions for the specific endogenous metabolic infrastructure of a host. We developed a novel web server, called MRE, which, for a given pair of starting and desired compounds in a given chassis organism, ranks biosynthesis routes from the perspective of the integration of new reactions into the endogenous metabolic system. For each promising heterologous biosynthesis pathway, MRE suggests actual enzymes for foreign metabolic reactions and generates information on competing endogenous reactions for the consumption of metabolites. These unique, chassis-centered features distinguish MRE from existing pathway design tools and allow synthetic biologists to evaluate the design of their biosynthesis systems from a different angle. By using biosynthesis of a range of high-value natural products as a case study, we show that MRE is an effective tool to guide the design and optimization of heterologous biosynthesis pathways. The URL of MRE is http://www.cbrc.kaust.edu.sa/mre/.

  2. MRE: a web tool to suggest foreign enzymes for the biosynthesis pathway design with competing endogenous reactions in mind

    KAUST Repository

    Kuwahara, Hiroyuki

    2016-04-29

    To rationally design a productive heterologous biosynthesis system, it is essential to consider the suitability of foreign reactions for the specific endogenous metabolic infrastructure of a host. We developed a novel web server, called MRE, which, for a given pair of starting and desired compounds in a given chassis organism, ranks biosynthesis routes from the perspective of the integration of new reactions into the endogenous metabolic system. For each promising heterologous biosynthesis pathway, MRE suggests actual enzymes for foreign metabolic reactions and generates information on competing endogenous reactions for the consumption of metabolites. These unique, chassis-centered features distinguish MRE from existing pathway design tools and allow synthetic biologists to evaluate the design of their biosynthesis systems from a different angle. By using biosynthesis of a range of high-value natural products as a case study, we show that MRE is an effective tool to guide the design and optimization of heterologous biosynthesis pathways. The URL of MRE is http://www.cbrc.kaust.edu.sa/mre/.

  3. Naturally occurring radionuclides in agricultural products: An overview

    International Nuclear Information System (INIS)

    Hanlon, E.A.

    1994-01-01

    Low levels of naturally occurring radionuclides exist in phosphatic clays, a by-product of phosphatic mining and beneficiation processes. Concerns about these radionuclides entering the human food chain were an immediate research priority before the phosphate clays could be reclaimed for intensive agricultural purposes. Efforts included the assembly of a large body of data from both sons and plants, part of which were produced by the Polk County (Florida) Mined Lands Agricultural Research/Demonstration Project MLAR/DP. Additional detailed studies involving dairy and beef cattle (Bos taurus) were conducted by researchers working with the MLAR/DP. A national symposium was conducted in which data concerning the MLAR/DP work and other research projects also dealing with naturally occurring radionuclides in agriculture could be discussed. The symposium included invited review papers dealing with the identification of radionuclide geological origins, the geochemistry and movement of radionuclides within the environment, mechanisms of plant uptake, entry points into the food chain, and evaluation of dose and risk assessment to the consumer of low levels of radionuclides. The risk to human health of an individual obtaining 0.1 of his or her dietary intake from crops produced on phosphatic clays increased by 1 in 5 x 10 6 /yr above a control individual consuming no food grown on phosphatic clays. Leaf tissues were found to be generally higher than fruit, grain, or root tissues. The natural range in radionuclide content among various food types was greater than the difference in radionuclides content between the same food produced on phosphatic clays vs. natural soils. 19 refs

  4. China's natural gas: Resources, production and its impacts

    International Nuclear Information System (INIS)

    Wang, Jianliang; Feng, Lianyong; Zhao, Lin; Snowden, Simon

    2013-01-01

    In order to achieve energy consumption targets, and subsequently reduce carbon emissions, China is working on energy strategies and policies aimed at actively increasing the consumption of natural gas—the lowest carbon energy of the fossil fuels, and to enhance the proportion of gas in total primary energy consumption. To do this, it is a necessary prerequisite that China must have access to adequate gas resources and production to meet demand. This paper shows that the availability of domestic gas resources are overestimated by China's authorities due to differences in classification and definitions of gas resources/reserves between China and those accepted internationally. Based on official gas resource figures, China's gas production remains low with respect to the projected demand, and will only be 164.6 bcm in 2020, far lower than the 375 bcm of forecast demand. The gap between gas production and demand will reach 210.4 bcm by 2020. Existing plans for the importation of gas and the development of unconventional gas will not close this gap in the next 10 years, and this situation will therefore present a severe challenge to China's gas security, achievement of targets in improving energy consumption structure and reducing carbon emissions. - Highlights: ► We show that available gas resources are overestimated by China's authorities. ► We forecast China's future gas production under different resource scenarios. ► This paper shows that China's gas production will not meet the soaring demand. ► The gap between supply and demand will continue to increase rapidly in future. ► China's gas security will meet a severe challenge because of this increasing gap

  5. Natural Occurrence of Aldol Condensation Products in Valencia Orange Oil.

    Science.gov (United States)

    Abreu, Ingo; Da Costa, Neil C; van Es, Alfred; Kim, Jung-A; Parasar, Uma; Poulsen, Mauricio L

    2017-12-01

    Cold pressed orange oils contain predominantly d-limonene (approximately 95%) and various other lower concentration monoterpenes, sesquiterpenes, sinensals plus 3 key aliphatic aldehydes: hexanal, octanal. and decanal. The aldol self-condensation products or "dimers" for each aldehyde have been postulated as being present at low concentrations in the oil. However, to date only the hexanal dimer has been previously reported. In this paper, cold pressed Valencia orange oil was fractionally distilled/folded and analyzed by GC and high resolution GC-MS to detect these compounds on 2 different capillary column phases. Subsequently the hexanal, octanal, and decanal self-aldol condensation products, 2-butyl-2-octenal, 2-hexyl-2-decenal, and 2-octyl-2-dodecenal, respectively, were detected in the folded oil. These predominantly trans configuration isomeric compounds were synthesized, to confirm them as being present in nature and evaluated organoleptically by a panel of evaluators. To further confirm the mechanism of their formation, the enriched oil was made into a simple beverage to show the effect on the formation of these aldol compounds under acidic conditions. Finally aliphatic aldehydes from hexanal to undecanal were reacted together in various combinatorial pairs to give an additional 33 self and mixed aldol condensation products, some of which were also detected in the folded oil. This paper discloses the structural elucidation and synthesis of 8 novel aldol condensation products found at trace concentrations in citrus and leading to a further 31 mass spectrally determined aldol products. Sensory evaluations and application of some of these components were demonstrated in a model citrus beverage. © 2017 Institute of Food Technologists®.

  6. Biosynthesis of fluorescent CdS nanocrystals with semiconductor properties: Comparison of microbial and plant production systems.

    Science.gov (United States)

    Al-Shalabi, Zahwa; Doran, Pauline M

    2016-04-10

    This study investigated fission yeast (Schizosaccharomyces pombe) and hairy roots of tomato (Solanum lycopersicum) as in vitro production vehicles for biological synthesis of CdS quantum dots. Cd added during the mid-growth phase of the cultures was detoxified within the biomass into inorganic sulphide-containing complexes with the quantum confinement properties of semiconductor nanocrystals. Significant differences were found between the two host systems in terms of nanoparticle production kinetics, yield and quality. The much slower growth rate of hairy roots compared with yeast is a disadvantage for commercial scaled-up production. Nanoparticle extraction from the biomass was less effective for the roots: 19% of the Cd present in the hairy roots was recovered after extraction compared with 34% for the yeast. The overall yield of CdS quantum dots was also lower for the roots: relative to the amount of Cd taken up into the biomass, 8.5% was recovered in yeast gel filtration fractions exhibiting quantum dot properties whereas the result for hairy roots was only 0.99%. Yeast-produced CdS crystallites were somewhat smaller with diameters of approximately 2-6 nm compared with those of 4-10nm obtained from the roots. The average ratio of inorganic sulphide to Cd for the purified and size-fractionated particles was 0.44 for the yeast and 1.6 for the hairy roots. Despite the limitations associated with hairy roots in terms of culture kinetics and product yield, this system produced CdS nanoparticles with enhanced photostability and 3.7-13-fold higher fluorescence quantum efficiency compared with those generated by yeast. This work demonstrates that the choice of cellular host can have a significant effect on nanoparticle functional properties as well as on the bioprocessing aspects of biological quantum dot synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Cholesterol overload impairing cerebellar function: the promise of natural products.

    Science.gov (United States)

    El-Sayyad, Hassan I H

    2015-05-01

    The cerebellum is the part of the brain most involved in controlling motor and cognitive function. The surface becomes convoluted, forming folia that have a characteristic internal structure of three layers including molecular, Purkinje cell, and granular layer. This complex neural network gives rise to a massive signal-processing capability. Cholesterol is a major constituent, derived by de novo synthesis and the blood-brain barrier. Cholesterol is tightly regulated between neurons and glia-that is, astrocytes, microglia, and oligodendrocytes-and is essential for normal brain development. The axon is wrapped by myelin (cholesterol, phospholipids, and glycosphingolipids) and made up of membranes of oligodendrocytes, separated by periodic gaps in the myelin sheath, called nodes of Ranvier. Hypercholesterolemia is associated with increased oxidative stress and the development of neurotoxicity and Alzheimer's disease. Treatment with natural products has been found to support improved brain function and reduce low-density-lipoprotein cholesterol level. Fish oil is one such product; among the many plant products are: Morus alba leaves, fruit, and bark; pomegranate fruit and peel; Barley β - glucans; date palm; and Allium sativum. The therapeutic potential was discussed in relation with the antilipidemic drugs, statins (HMG-CoA reductase inhibitors). Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Does Osmotic Stress Affect Natural Product Expression in Fungi?

    Science.gov (United States)

    Overy, David; Correa, Hebelin; Roullier, Catherine; Chi, Wei-Chiung; Pang, Ka-Lai; Rateb, Mostafa; Ebel, Rainer; Shang, Zhuo; Capon, Rob; Bills, Gerald; Kerr, Russell

    2017-08-13

    The discovery of new natural products from fungi isolated from the marine environment has increased dramatically over the last few decades, leading to the identification of over 1000 new metabolites. However, most of the reported marine-derived species appear to be terrestrial in origin yet at the same time, facultatively halo- or osmotolerant. An unanswered question regarding the apparent chemical productivity of marine-derived fungi is whether the common practice of fermenting strains in seawater contributes to enhanced secondary metabolism? To answer this question, a terrestrial isolate of Aspergillus aculeatus was fermented in osmotic and saline stress conditions in parallel across multiple sites. The ex-type strain of A. aculeatus was obtained from three different culture collections. Site-to-site variations in metabolite expression were observed, suggesting that subculturing of the same strain and subtle variations in experimental protocols can have pronounced effects upon metabolite expression. Replicated experiments at individual sites indicated that secondary metabolite production was divergent between osmotic and saline treatments. Titers of some metabolites increased or decreased in response to increasing osmolite (salt or glycerol) concentrations. Furthermore, in some cases, the expression of some secondary metabolites in relation to osmotic and saline stress was attributed to specific sources of the ex-type strains.

  9. De Novo Deep Transcriptome Analysis of Medicinal Plants for Gene Discovery in Biosynthesis of Plant Natural Products.

    Science.gov (United States)

    Han, R; Rai, A; Nakamura, M; Suzuki, H; Takahashi, H; Yamazaki, M; Saito, K

    2016-01-01

    Study on transcriptome, the entire pool of transcripts in an organism or single cells at certain physiological or pathological stage, is indispensable in unraveling the connection and regulation between DNA and protein. Before the advent of deep sequencing, microarray was the main approach to handle transcripts. Despite obvious shortcomings, including limited dynamic range and difficulties to compare the results from distinct experiments, microarray was widely applied. During the past decade, next-generation sequencing (NGS) has revolutionized our understanding of genomics in a fast, high-throughput, cost-effective, and tractable manner. By adopting NGS, efficiency and fruitful outcomes concerning the efforts to elucidate genes responsible for producing active compounds in medicinal plants were profoundly enhanced. The whole process involves steps, from the plant material sampling, to cDNA library preparation, to deep sequencing, and then bioinformatics takes over to assemble enormous-yet fragmentary-data from which to comb and extract information. The unprecedentedly rapid development of such technologies provides so many choices to facilitate the task, which can cause confusion when choosing the suitable methodology for specific purposes. Here, we review the general approaches for deep transcriptome analysis and then focus on their application in discovering biosynthetic pathways of medicinal plants that produce important secondary metabolites. © 2016 Elsevier Inc. All rights reserved.

  10. Natural sweetening of food products by engineering Lactococcus lactis for glucose production

    NARCIS (Netherlands)

    Pool, Wietske A.; Neves, Ana Rute; Kok, Jan; Santos, Helena; Kuipers, Oscar P.

    We show that sweetening of food products by natural fermentation can be achieved by a combined metabolic engineering and transcriptome analysis approach. A Lactococcus lactis ssp. cremoris strain was constructed in which glucose metabolism was completely disrupted by deletion of the genes coding for

  11. Lightweight Approaches to Natural Gas Hydrate Exploration & Production

    Science.gov (United States)

    Max, M. D.; Johnson, A. H.

    2017-12-01

    Lower-cost approaches to drilling and reservoir utilization are made possible by adapting both emerging and new technology to the unique, low risk NGH natural gas resource. We have focused on drilling, wellbore lining technology, and reservoir management with an emphasis on long-term sand control and adaptive mechanical stability during NGH conversion to its constituent gas and water. In addition, we suggest that there are opportunities for management of both the gas and water with respect to maintaining desired thermal conditions. Some of the unique aspects of NGH deposits allow for new, more efficient technology to be applied to development, particularly in drilling. While NGH-bearing sands are in deepwater, they are confined to depths beneath the seafloor of 1.2 kilometers or less. As a result, they will not be significantly above hydrostatic pressure, and temperatures will be less than 30 oC. Drilling will be through semi-consolidated sediment without liquid hydrocarbons. These characteristics mean that high capability drillships are not needed. What is needed is a new perspective about drilling and producing NGH. Drilling from the seafloor will resolve the high-pressure differential between a wellhead on the sea surface in a vessel and reservoir to about the hydrostatic pressure difference between the seafloor and, at most, the base of the GHSZ. Although NGH production will begin using "off-the-shelf" technology, innovation will lead to new technology that will bring down costs and increase efficiency in the same way that led to the shale breakthrough. Commercial success is possible if consideration is given to what is actually needed to produce NGH in a safe and environmentally manner. Max, M.D. 2017. Wellbore Lining for Natural Gas Hydrate. U.S. Patent Application US15644947 Max, M.D. & Johnson, A.H. 2017. E&P Cost Reduction Opportunities for Natural Gas Hydrate. OilPro. . Max, M.D. & Johnson, A.H. 2016. Exploration and Production of Oceanic Natural Gas

  12. Citrus fruit flavor and aroma biosynthesis: isolation, functional characterization, and developmental regulation of Cstps1, a key gene in the production of the sesquiterpene aroma compound valencene.

    Science.gov (United States)

    Sharon-Asa, Liat; Shalit, Moshe; Frydman, Ahuva; Bar, Einat; Holland, Doron; Or, Etti; Lavi, Uri; Lewinsohn, Efraim; Eyal, Yoram

    2003-12-01

    Citrus fruits possess unique aromas rarely found in other fruit species. While fruit flavor is composed of complex combinations of soluble and volatile compounds, several low-abundance sesquiterpenes, such as valencene, nootkatone, alpha-sinensal, and beta-sinensal, stand out in citrus as important flavor and aroma compounds. The profile of terpenoid volatiles in various citrus species and their importance as aroma compounds have been studied in detail, but much is still lacking in our understanding of the physiological, biochemical, and genetic regulation of their production. Here, we report on the isolation, functional expression, and developmental regulation of Cstps1, a sesquiterpene synthase-encoding gene, involved in citrus aroma formation. The recombinant enzyme encoded by Cstps1 was shown to convert farnesyl diphosphate to a single sesquiterpene product identified as valencene by gas chromatography-mass spectrometry (GC-MS). Phylogenetic analysis of plant terpene synthase genes localized Cstps1 to the group of angiosperm sesquiterpene synthases. Within this group, Cstps1 belongs to a subgroup of citrus sesquiterpene synthases. Cstps1 was found to be developmentally regulated: transcript was found to accumulate only towards fruit maturation, corresponding well with the timing of valencene accumulation in fruit. Although citrus fruits are non-climacteric, valencene accumulation and Cstps1 expression were found to be responsive to ethylene, providing further evidence for the role of ethylene in the final stages of citrus fruit ripening. Isolation of the gene encoding valencene synthase provides a tool for an in-depth study of the regulation of aroma compound biosynthesis in citrus and for metabolic engineering for fruit flavor characteristics.

  13. Studies on the biosynthesis of lignins and their production in plant cell cultures. [Forsythia intermedia; Podophyllum hexandrum; Podophyllum peltatum

    Energy Technology Data Exchange (ETDEWEB)

    Abdul-Rahman, M.M.

    1988-01-01

    Phytochemical analysis of Forsythia intermedia tissues has demonstrated the presence of lignins of the dibenzylbutyrolactone and dioxabicyclo(3,3,0)octane classes, together with their O-glucosides. Lignin distribution in different parts of the part, and variation with the season has been recorded. Cell suspension cultures from F. intermedia were developed. These also synthesized lignins, though not the full range as found in the fresh tissues. Culture lines synthesizing either matairesinol 4{prime}-O-glucoside and major lignin components were established. These cultures rapidly metabolized exogenous lignins without producing detectable lignin transformation products. The seasonal variation in aryltetralin lactone levels in young plants Podophyllum hexandrum and P. peltatum has been investigated. Cell cultures of the plants were established, but no lignins were detectable in them. However, a protocol for micropropagation via embryoid production was obtained. Feeding experiments in P. hexandrum plants showed that matairesinol was a precursor of both podophyllotoxin and 4{prime}-demethylpodophyllotoxin, thus indicating it to be a common precursor of the trimethoxy and hydroxydimethoxy series of lignins in this plant. Precursor feeding experiments with {sup 3}H/{sup 14}C-labeled coniferyl alcohol showed an unexpected increase in {sup 3}H/{sup 14}C ratio when incorporated into both Forsythia and Podophyllum lignins.

  14. Marine Natural Products from New Caledonia—A Review

    Directory of Open Access Journals (Sweden)

    Sofia-Eléna Motuhi

    2016-03-01

    Full Text Available Marine micro- and macroorganisms are well known to produce metabolites with high biotechnological potential. Nearly 40 years of systematic prospecting all around the New Caledonia archipelago and several successive research programs have uncovered new chemical leads from benthic and planktonic organisms. After species identification, biological and/or pharmaceutical analyses are performed on marine organisms to assess their bioactivities. A total of 3582 genera, 1107 families and 9372 species have been surveyed and more than 350 novel molecular structures have been identified. Along with their bioactivities that hold promise for therapeutic applications, most of these molecules are also potentially useful for cosmetics and food biotechnology. This review highlights the tremendous marine diversity in New Caledonia, and offers an outline of the vast possibilities for natural products, especially in the interest of pursuing collaborative fundamental research programs and developing local biotechnology programs.

  15. Inhibitors of Microglial Neurotoxicity: Focus on Natural Products

    Directory of Open Access Journals (Sweden)

    Kyoungho Suk

    2011-01-01

    Full Text Available Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels.

  16. The Complexity of Bioactive Natural Products in Plants

    DEFF Research Database (Denmark)

    Frisch, Tina

    Plants produce a diverse range of bioactive natural products promoting their fitness. These specialized metabolites may serve as chemical defence against herbivores and pathogens and may inhibit the growth and development of competing species. Hydroxynitrile glucosides and glucosinolates are two...... classes of defence compounds, which have diverging properties, but also share common biosynthetic features. Hydroxynitrile glucosides are produced in species across the plant kingdom, whereas glucosinolates are found almost exclusively within the Brassicales, which generally does not contain...... hydroxynitrile glucosides. This division has raised questions regarding possible evolutionary relationships between the biosynthetic pathways. The very rare co-occurrence of hydroxynitrile glucosides and glucosinolates found in Alliaria petiolata (garlic mustard, løgkarse) and Carica papaya (papaya) makes...

  17. Role of Antioxidants and Natural Products in Inflammation

    Directory of Open Access Journals (Sweden)

    Palanisamy Arulselvan

    2016-01-01

    Full Text Available Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.

  18. Influenza neuraminidase: a druggable target for natural products.

    Science.gov (United States)

    Grienke, Ulrike; Schmidtke, Michaela; von Grafenstein, Susanne; Kirchmair, Johannes; Liedl, Klaus R; Rollinger, Judith M

    2012-01-01

    The imminent threat of influenza pandemics and repeatedly reported emergence of new drug-resistant influenza virus strains demonstrate the urgent need for developing innovative and effective antiviral agents for prevention and treatment. At present, influenza neuraminidase (NA), a key enzyme in viral replication, spread, and pathogenesis, is considered to be one of the most promising targets for combating influenza. Despite the substantial medical potential of NA inhibitors (NAIs), only three of these drugs are currently on the market (zanamivir, oseltamivir, and peramivir). Moreover, sudden changes in NAI susceptibility revealed the urgent need in the discovery/identification of novel inhibitors. Nature offers an abundance of biosynthesized compounds comprising chemical scaffolds of high diversity, which present an infinite pool of chemical entities for target-oriented drug discovery in the battle against this highly contagious pathogen. This review illuminates the increasing research efforts of the past decade (2000-2011), focusing on the structure, function and druggability of influenza NA, as well as its inhibition by natural products. Following a critical discussion of publications describing some 150 secondary plant metabolites tested for their inhibitory potential against influenza NA, the impact of three different strategies to identify and develop novel NAIs is presented: (i) bioactivity screening of herbal extracts, (ii) exploitation of empirical knowledge, and (iii) computational approaches. This work addresses the latest developments in theoretical and experimental research on properties of NA that are and will be driving anti-influenza drug development now and in the near future.

  19. Toxic element contamination of natural health products and pharmaceutical preparations.

    Directory of Open Access Journals (Sweden)

    Stephen J Genuis

    Full Text Available BACKGROUND: Concern has recently emerged regarding the safety of natural health products (NHPs-therapies that are increasingly recommended by various health providers, including conventional physicians. Recognizing that most individuals in the Western world now consume vitamins and many take herbal agents, this study endeavored to determine levels of toxic element contamination within a range of NHPs. METHODS: Toxic element testing was performed on 121 NHPs (including Ayurvedic, traditional Chinese, and various marine-source products as well as 49 routinely prescribed pharmaceutical preparations. Testing was also performed on several batches of one prenatal supplement, with multiple samples tested within each batch. Results were compared to existing toxicant regulatory limits. RESULTS: Toxic element contamination was found in many supplements and pharmaceuticals; levels exceeding established limits were only found in a small percentage of the NHPs tested and none of the drugs tested. Some NHPs demonstrated contamination levels above preferred daily endpoints for mercury, cadmium, lead, arsenic or aluminum. NHPs manufactured in China generally had higher levels of mercury and aluminum. CONCLUSIONS: Exposure to toxic elements is occurring regularly as a result of some contaminated NHPs. Best practices for quality control-developed and implemented by the NHP industry with government oversight-is recommended to guard the safety of unsuspecting consumers.

  20. Core@shell Nanoparticles: Greener Synthesis Using Natural Plant Products

    Directory of Open Access Journals (Sweden)

    Mehrdad Khatami

    2018-03-01

    Full Text Available Among an array of hybrid nanoparticles, core-shell nanoparticles comprise of two or more materials, such as metals and biomolecules, wherein one of them forms the core at the center, while the other material/materials that were located around the central core develops a shell. Core-shell nanostructures are useful entities with high thermal and chemical stability, lower toxicity, greater solubility, and higher permeability to specific target cells. Plant or natural products-mediated synthesis of nanostructures refers to the use of plants or its extracts for the synthesis of nanostructures, an emerging field of sustainable nanotechnology. Various physiochemical and greener methods have been advanced for the synthesis of nanostructures, in contrast to conventional approaches that require the use of synthetic compounds for the assembly of nanostructures. Although several biological resources have been exploited for the synthesis of core-shell nanoparticles, but plant-based materials appear to be the ideal candidates for large-scale green synthesis of core-shell nanoparticles. This review summarizes the known strategies for the greener production of core-shell nanoparticles using plants extract or their derivatives and highlights their salient attributes, such as low costs, the lack of dependence on the use of any toxic materials, and the environmental friendliness for the sustainable assembly of stabile nanostructures.

  1. Detection of phytohormones in temperate forest fungi predicts consistent abscisic acid production and a common pathway for cytokinin biosynthesis.

    Science.gov (United States)

    Morrison, Erin N; Knowles, Sarah; Hayward, Allison; Thorn, R Greg; Saville, Barry J; Emery, R J N

    2015-01-01

    The phytohormones, abscisic acid and cytokinin, once were thought to be present uniquely in plants, but increasing evidence suggests that these hormones are present in a wide variety of organisms. Few studies have examined fungi for the presence of these "plant" hormones or addressed whether their levels differ based on the nutrition mode of the fungus. This study examined 20 temperate forest fungi of differing nutritional modes (ectomycorrhizal, wood-rotting, saprotrophic). Abscisic acid and cytokinin were present in all fungi sampled; this indicated that the sampled fungi have the capacity to synthesize these two classes of phytohormones. Of the 27 cytokinins analyzed by HPLC-ESI MS/MS, seven were present in all fungi sampled. This suggested the existence of a common cytokinin metabolic pathway in fungi that does not vary among different nutritional modes. Predictions regarding the source of isopentenyl, cis-zeatin and methylthiol CK production stemming from the tRNA degradation pathway among fungi are discussed. © 2015 by The Mycological Society of America.

  2. Production of polyhydroxybutyrate in oil palm (Elaeis guineensis Jacq. mediated by microprojectile bombardment of PHB biosynthesis genes into embryogenic calli

    Directory of Open Access Journals (Sweden)

    Ahmad Parveez eGhulam Kadir

    2015-08-01

    Full Text Available Biodegradable plastics, mainly polyhydroxybutyrate (PHB, which are traditionally produced by bacterial cells, have been produced in the cells of more than 15 plant species. Since the production of biodegradable plastics and the synthesis of oil in plants share the same substrate, acetyl-coenzyme A (acetyl-CoA, producing PHB in oil bearing crops, such as oil palm, will be advantageous. In this study, three bacterial genes, bktB, phaB and phaC, which are required for the synthesis of PHB and selectable marker gene, bar, for herbicide Basta resistant, were transformed into embryogenic calli. A number of transformed embryogenic lines resistant to herbicide Basta were obtained and were later regenerated to produce few hundred plantlets. Molecular analyses, including PCR, Southern blot and real-time PCR have demonstrated stable integration and expression of the transgenes in the oil palm genome. HPLC and Nile Blue A staining analyses confirmed the synthesis of PHB in some of the plantlets.

  3. Production of polyhydroxybutyrate in oil palm (Elaeis guineensis Jacq.) mediated by microprojectile bombardment of PHB biosynthesis genes into embryogenic calli

    Science.gov (United States)

    Parveez, Ghulam Kadir Ahmad; Bahariah, Bohari; Ayub, Nor Hanin; Masani, Mat Yunus Abdul; Rasid, Omar Abdul; Tarmizi, Ahmad Hashim; Ishak, Zamzuri

    2015-01-01

    Biodegradable plastics, mainly polyhydroxybutyrate (PHB), which are traditionally produced by bacterial cells, have been produced in the cells of more than 15 plant species. Since the production of biodegradable plastics and the synthesis of oil in plants share the same substrate, acetyl-coenzyme A (acetyl-CoA), producing PHB in oil bearing crops, such as oil palm, will be advantageous. In this study, three bacterial genes, bktB, phaB, and phaC, which are required for the synthesis of PHB and selectable marker gene, bar, for herbicide Basta resistant, were transformed into embryogenic calli. A number of transformed embryogenic lines resistant to herbicide Basta were obtained and were later regenerated to produce few hundred plantlets. Molecular analyses, including polymerase chain reaction (PCR), Southern blot, and real-time PCR have demonstrated stable integration and expression of the transgenes in the oil palm genome. HPLC and Nile blue A staining analyses confirmed the synthesis of PHB in some of the plantlets. PMID:26322053

  4. Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol

    Directory of Open Access Journals (Sweden)

    Meiya Li

    2015-01-01

    Full Text Available Taxadiene is the first committed precursor to paclitaxel, marketed as Taxol, arguably the most important anticancer agent against ovarian and breast cancer. In Taxus, taxadiene is directly synthesized from geranylgeranyl diphosphate (GGPP that is the common precursor for diterpenoids and is found in most plants and microbes. In this study, Artemisia annua L., a Chinese medicinal herb that grows fast and is rich in terpenoids, was used as a genetic engineering host to produce taxadiene. The TXS (taxadiene synthase gene, cloned from Taxus and inserted into pCAMBIA1304, was transformed into Artemisia annua L. using the Agrobacterium tumefaciens-mediated method. Thirty independent transgenic plants were obtained, and GC-MS analysis was used to confirm that taxadiene was produced and accumulated up to 129.7 μg/g dry mass. However, the high expression of TXS did not affect plant growth or photosynthesis in transgenic Artemisia annua L. It is notable that artemisinin is produced and stored in leaves and most taxadiene accumulated in the stem of transgenic Artemisia annua L., suggesting a new way to produce two important compounds in one transgenic plant: leaves for artemisinin and stem for taxadiene. Overall, this study demonstrates that genetic engineering of the taxane biosynthetic pathway in Artemisia annua L. for the production of taxadiene is feasible.

  5. Biosynthesis of oleamide.

    Science.gov (United States)

    Mueller, Gregory P; Driscoll, William J

    2009-01-01

    Oleamide (cis-9-octadecenamide) is the prototype long chain primary fatty acid amide lipid messenger. The natural occurrence of oleamide was first reported in human serum in 1989. Subsequently oleamide was shown to accumulate in the cerebrospinal fluid of sleep-deprived cats and to induce sleep when administered to experimental animals. Accordingly, oleamide first became known for its potential role in the mechanisms that mediate the drive to sleep. Oleamide also has profound effects on thermoregulation and acts as an analgesic in several models of experimental pain. Although these important pharmacologic effects are well establish, the biochemical mechanism for the synthesis of oleamide has not yet been defined. This chapter reviews the biosynthetic pathways that have been proposed and highlights two mechanisms which are most supported by experimental evidence: the generation of oleamide from oleoylglycine by the neuropeptide processing enzyme, peptidylglycine alpha-amidating monooxygenase (PAM), and alternatively, the direct amidation of oleic acid via oleoyl coenzyme A by cytochrome c using ammonia as the nitrogen source. The latter mechanism is discussed in the context of apoptosis where oleamide may play a role in regulating gap junction communication. Lastly, several considerations and caveats pertinent to the future study oleamide biosynthesis are discussed.

  6. PCR screening reveals considerable unexploited biosynthetic potential of ansamycins and a mysterious family of AHBA-containing natural products in actinomycetes.

    Science.gov (United States)

    Wang, H-X; Chen, Y-Y; Ge, L; Fang, T-T; Meng, J; Liu, Z; Fang, X-Y; Ni, S; Lin, C; Wu, Y-Y; Wang, M-L; Shi, N-N; He, H-G; Hong, K; Shen, Y-M

    2013-07-01

    Ansamycins are a family of macrolactams that are synthesized by type I polyketide synthase (PKS) using 3-amino-5-hydroxybenzoic acid (AHBA) as the starter unit. Most members of the family have strong antimicrobial, antifungal, anticancer and/or antiviral activities. We aimed to discover new ansamycins and/or other AHBA-containing natural products from actinobacteria. Through PCR screening of AHBA synthase gene, we identified 26 AHBA synthase gene-positive strains from 206 plant-associated actinomycetes (five positives) and 688 marine-derived actinomycetes (21 positives), representing a positive ratio of 2·4-3·1%. Twenty-five ansamycins, including eight new compounds, were isolated from six AHBA synthase gene-positive strains through TLC-guided fractionations followed by repeated column chromatography. To gain information about those potential ansamycin gene clusters whose products were unknown, seven strains with phylogenetically divergent AHBA synthase genes were subjected to fosmid library construction. Of the seven gene clusters we obtained, three show characteristics for typical ansamycin gene clusters, and other four, from Micromonospora spp., appear to lack the amide synthase gene, which is unusual for ansamycin biosynthesis. The gene composition of these four gene clusters suggests that they are involved in the biosynthesis of a new family of hybrid PK-NRP compounds containing AHBA substructure. PCR screening of AHBA synthase is an efficient approach to discover novel ansamycins and other AHBA-containing natural products. This work demonstrates that the AHBA-based screening method is a useful approach for discovering novel ansamycins and other AHBA-containing natural products from new microbial resources. Journal of Applied Microbiology © 2013 The Society for Applied Microbiology.

  7. Effects of bioenergy production on European nature conservation options

    Science.gov (United States)

    Schleupner, C.; Schneider, U. A.

    2009-04-01

    To increase security of energy supply and reduce greenhouse gas (GHG) emissions the European Commission set out a long-term strategy for renewable energy in the European Union (EU). Bioenergy from forestry and agriculture plays a key role for both. Since the last decade a significant increase of biomass energy plantations has been observed in Europe. Concurrently, the EU agreed to halt the loss of biodiversity within its member states. One measure is the Natura2000 network of important nature sites that actually covers about 20% of the EU land surface. However, to fulfil the biodiversity target more nature conservation and restoration sites need to be designated. There are arising concerns that an increased cultivation of bioenergy crops will decrease the land available for nature reserves and for "traditional" agriculture and forestry. In the following the economic and ecological impacts of structural land use changes are demonstrated by two examples. First, a case study of land use changes on the Eiderstedt peninsula in Schleswig-Holstein/Germany evaluates the impacts of grassland conversion into bioenergy plantations under consideration of selected meadow birds. Scenarios indicate not only a quantitative loss of habitats but also a reduction of habitat quality. The second study assesses the role of bioenergy production in light of possible negative impacts on potential wetland conservation sites in Europe. By coupling the spatial wetland distribution model "SWEDI" (cf. SCHLEUPNER 2007) to the European Forest and Agricultural Sector Optimization Model (EUFASOM; cf. SCHNEIDER ET AL. 2008) economic and environmental aspects of land use are evaluated simultaneously. This way the costs and benefits of the appropriate measures and its consequences for agriculture and forestry are investigated. One aim is to find the socially optimal balance between alternative wetland uses by integrating biological benefits - in this case wetlands - and economic opportunities - here

  8. Glycolipid biosynthesis in cyanobacteria

    International Nuclear Information System (INIS)

    Van Dusen, W.J.; Jaworski, J.G.

    1987-01-01

    The biosynthesis of monogalactosyldiacyl-glycerol (MGDG) was studied in five different cyanobacteria. Previous work has shown Anabaena variabilis to synthesize both MGDG and monoglucosyl-diacylglycerol (MG1cDG) with MG1cDG being the precursor of MGDG. They have examined four other cyanobacteria to determine if a similar relationship exists. The cyanobacteria studied were Anabaena variabilis, Chlorogloeopsis sp., Schizothrix calcicola, Anacystis nidulans, and Anacystis marina. Each were grown in liquid culture and lipids were labeled with 14 C]CO 2 for 20 min., 1.0 hr, 1.0 hr + 10 hr chase. Glycolipids were analyzed by initial separation of MGDG and MG1cDG by TLC followed by further analysis by HPLC. Complete separation of molecular species was obtained isocratically on an ODS column. All of the cyanobacteria labeled 16-C and 18-C fatty acids except for A. marina which labeled only 14-C and 16-C fatty acids. Desaturation of the fatty acids could be observed in the 1.0 hr and chase experiments. All were capable of labeling both MG1cDG and MGDG with the precursor-product relationship being observed. There does not appear to be a direct relationship between the epimerization of the sugar moiety and fatty acid desaturation

  9. A systematic review of natural health product treatment for vitiligo

    Directory of Open Access Journals (Sweden)

    Boon Heather S

    2008-05-01

    Full Text Available Abstract Background Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected. Methods Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality. Results Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1 L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2 Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3 Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4 Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting. Conclusion Reports investigating the

  10. Discovery, biosynthesis, and rational engineering of novel enterocin and wailupemycin polyketide analogues.

    Science.gov (United States)

    Kalaitzis, John A

    2013-01-01

    The marine actinomycete Streptomyces maritimus produces a structurally diverse set of unusual polyketide natural products including the major metabolite enterocin. Investigations of enterocin biosynthesis revealed that the unique carbon skeleton is derived from an aromatic polyketide pathway which is genetically coded by the 21.3 kb enc gene cluster in S. maritimus. Characterization of the enc biosynthesis gene cluster and subsequent manipulation of it via heterologous expression and/or mutagenesis enabled the discovery of other enc-based metabolites that were produced in only very minor amounts in the wild type. Also described are techniques used to harness the enterocin biosynthetic machinery in order to generate unnatural enc-derived polyketide analogues. This review focuses upon the molecular methods used in combination with classical natural products detection and isolation techniques to access minor metabolites of the S. maritimus secondary metabolome.

  11. Enabling techniques in the search for new antibiotics: Combinatorial biosynthesis of sugar-containing antibiotics.

    Science.gov (United States)

    Park, Je Won; Nam, Sang-Jip; Yoon, Yeo Joon

    2017-06-15

    Nature has a talent for inventing a vast number of natural products, including hybrids generated by blending different scaffolds, resulting in a myriad of bioactive chemical entities. Herein, we review the highlights and recent trends (2010-2016) in the combinatorial biosynthesis of sugar-containing antibiotics where nature's structural diversification capabilities are exploited to enable the creation of new anti-infective and anti-proliferative drugs. In this review, we describe the modern combinatorial biosynthetic approaches for polyketide synthase-derived complex and aromatic polyketides, non-ribosomal peptide synthetase-directed lipo-/glycopeptides, aminoglycosides, nucleoside antibiotics, and alkaloids, along with their therapeutic potential. Finally, we present the feasible nexus between combinatorial biosynthesis, systems biology, and synthetic biology as a toolbox to provide new antibiotics that will be indispensable in the post-antibiotic era. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Natural Products as Leads in Schistosome Drug Discovery

    Directory of Open Access Journals (Sweden)

    Bruno J. Neves

    2015-01-01

    Full Text Available Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ, the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

  13. Identification and quantification of the halogenated natural product BC-3

    Energy Technology Data Exchange (ETDEWEB)

    Melcher, J.; Olbrich, D.; Vetter, W. [Hohenheim Univ., Stuttgart (Germany). Inst. fuer Lebensmittelchemie; Marsh, G. [Stockholm Univ. (Sweden). Dept. of Environmental Chemistry; Gaus, C.; Mueller, J.F. [National Research Centre for Environmental Toxicology, Coopers Plains (Australia)

    2004-09-15

    Halogenated natural products (HNPs) of marine origin are increasingly recognized as critical residues in foodstuff (e. g. fish) and environmental samples (e. g. marine mammals and birds). Some of these HNPs (Q1, MHC-1, BC-2, and HDBPs including BC-10) were detected in diverse fish and marine mammal samples at concentrations sometimes exceeding those of PCBs, DDT, and other anthropogenic pollutants. Recent studies with marine mammal samples from Australia led to the detection of six abundant HNPs (Q1, BC-1, BC-2, BC-3, BC-10, and BC-11). In the meantime, Q1 was identified as heptachloro-1{sup '}-methyl-1,2{sup '}-bipyrrole, BC-2 as 4,6-dibromo-2-(2{sup '},4{sup '}-dibromo)phenoxyanisole, BC- 10 as 1,1{sup '}-dimethyl-3,3{sup '},4,4{sup '}-tetrabromo-5,5{sup '}-dichloro-2,2{sup '}-bipyrrole, and BC-11 as 3,5-dibromo- 2-(3{sup '},5{sup '}-dibromo,2{sup '}-methoxy)phenoxyanisole. However the identity of BC-1 and BC-3 remained unclear. The goal of the present study was the identification of BC-3. The tetrabromo compound BC-3 has previously been detected in marine mammals from four continents. Furthermore, we attempted establishing quantitative concentrations in diverse marine biota samples.

  14. Formulating natural based cosmetic product - irradiated herbal lip balm

    International Nuclear Information System (INIS)

    Seri Chempaka Mohd Yusof; Ros Anita Ahmad Ramli; Foziah Ali; Zainab Harun

    2007-01-01

    Herbal lip balm was formulated in efforts to produce a safe product, attractive with multifunctional usage i.e. prevent chap lips, reduce mouth odour and benefits in improving the health quality. Problems faced in constructing formulations of herbal lip balm were focused to the extraction of anthocyanins, the stability of the pigments in the formulations and changes of colour during irradiation for the sterilization of herbal lip balm. Natural pigment, anthocyanin was used as a colorant agent in herbal lip balm, obtained from various herbs and vegetables i.e. Hibiscus sabdariffa L. (roselle), Brassica oleracea var. capitata f. rubra (red cabbage) and Daucus carota (carrot). Water based extraction method was used in extracting the anthocyanins. The incorporation of honey in the formulations improved the colour of the lip balm. The usage of plant based ingredient i.e. cocoa butter substituting the normal based ingredient i.e. petroleum jelly in lip balm also affecting the colour of herbal lip balm. Irradiation at 2.5, 5.0 and 10 kGy was carried out as preservation and reducing of microbial load of the herbal lip balm and changes in colour were observed in formulations irradiated at 10 kGy. (Author)

  15. Natural products as a resource for biologically active compounds

    International Nuclear Information System (INIS)

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod) 3 is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous 13 C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the 1 H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants

  16. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

    Directory of Open Access Journals (Sweden)

    Scott B Vafai

    Full Text Available Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS. Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

  17. Plants’ Natural Products as Alternative Promising Anti-Candida Drugs

    Science.gov (United States)

    Soliman, Sameh; Alnajdy, Dina; El-Keblawy, Ali A.; Mosa, Kareem A.; Khoder, Ghalia; Noreddin, Ayman M.

    2017-01-01

    Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID:28989245

  18. Natural Products for the Treatment of Chlamydiaceae Infections

    Directory of Open Access Journals (Sweden)

    Mika A. Brown

    2016-10-01

    Full Text Available Due to the global prevalence of Chlamydiae, exploring studies of diverse antichlamydial compounds is important in the development of effective treatment strategies and global infectious disease management. Chlamydiaceae is the most widely known bacterial family of the Chlamydiae order. Among the species in the family Chlamydiaceae, Chlamydia trachomatis and Chlamydia pneumoniae cause common human diseases, while Chlamydia abortus, Chlamydia psittaci, and Chlamydia suis represent zoonotic threats or are endemic in human food sources. Although chlamydial infections are currently manageable in human populations, chlamydial infections in livestock are endemic and there is significant difficulty achieving effective treatment. To combat the spread of Chlamydiaceae in humans and other hosts, improved methods for treatment and prevention of infection are needed. There exist various studies exploring the potential of natural products for developing new antichlamydial treatment modalities. Polyphenolic compounds can inhibit chlamydial growth by membrane disruption, reestablishment of host cell apoptosis, or improving host immune system detection. Fatty acids, monoglycerides, and lipids can disrupt the cell membranes of infective chlamydial elementary bodies (EBs. Peptides can disrupt the cell membranes of chlamydial EBs, and transferrins can inhibit chlamydial EBs from attachment to and permeation through the membranes of host cells. Cellular metabolites and probiotic bacteria can inhibit chlamydial infection by modulating host immune responses and directly inhibiting chlamydial growth. Finally, early stage clinical trials indicate that polyherbal formulations can be effective in treating chlamydial infections. Herein, we review an important body of literature in the field of antichlamydial research.

  19. An analysis of FDA-approved drugs: natural products and their derivatives.

    Science.gov (United States)

    Patridge, Eric; Gareiss, Peter; Kinch, Michael S; Hoyer, Denton

    2016-02-01

    Natural products contribute greatly to the history and landscape of new molecular entities (NMEs). An assessment of all FDA-approved NMEs reveals that natural products and their derivatives represent over one-third of all NMEs. Nearly one-half of these are derived from mammals, one-quarter from microbes and one-quarter from plants. Since the 1930s, the total fraction of natural products has diminished, whereas semisynthetic and synthetic natural product derivatives have increased. Over time, this fraction has also become enriched with microbial natural products, which represent a significant portion of approved antibiotics, including more than two-thirds of all antibacterial NMEs. In recent years, the declining focus on natural products has impacted the pipeline of NMEs from specific classes, and this trend is likely to continue without specific investment in the pursuit of natural products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Metabolic engineering for improved heterologous terpenoid biosynthesis

    NARCIS (Netherlands)

    Ryden, A.; Melillo, E.; Czepnik, M.; Kayser, O.

    Terpenoids belong to the largest class of natural compounds and are produced in all living organisms. The isoprenoid skeleton is based on assembling of C5 building blocks, but the biosynthesis of a great variety of terpenoids ranging from monoterpenoids to polyterpenoids is not fully understood

  1. Biosynthesis of rare hexoses using microorganisms and related enzymes

    Science.gov (United States)

    Li, Zijie; Gao, Yahui; Nakanishi, Hideki

    2013-01-01

    Summary Rare sugars, referred to as monosaccharides and their derivatives that rarely exist in nature, can be applied in many areas ranging from foodstuffs to pharmaceutical and nutrition industry, or as starting materials for various natural products and drug candidates. Unfortunately, an important factor restricting the utilization of rare sugars is their limited availability, resulting from limited synthetic methods. Nowadays, microbial and enzymatic transformations have become a very powerful tool in this field. This article reviews the biosynthesis and enzymatic production of rare ketohexoses, aldohexoses and sugar alcohols (hexitols), including D-tagatose, D-psicose, D-sorbose, L-tagatose, L-fructose, 1-deoxy-L-fructose, D-allose, L-glucose, L-talose, D-gulose, L-galactose, L-fucose, allitol, D-talitol, and L-sorbitol. New systems and robust catalysts resulting from advancements in genomics and bioengineering are also discussed. PMID:24367410

  2. Biosynthesis of rare hexoses using microorganisms and related enzymes

    Directory of Open Access Journals (Sweden)

    Zijie Li

    2013-11-01

    Full Text Available Rare sugars, referred to as monosaccharides and their derivatives that rarely exist in nature, can be applied in many areas ranging from foodstuffs to pharmaceutical and nutrition industry, or as starting materials for various natural products and drug candidates. Unfortunately, an important factor restricting the utilization of rare sugars is their limited availability, resulting from limited synthetic methods. Nowadays, microbial and enzymatic transformations have become a very powerful tool in this field. This article reviews the biosynthesis and enzymatic production of rare ketohexoses, aldohexoses and sugar alcohols (hexitols, including D-tagatose, D-psicose, D-sorbose, L-tagatose, L-fructose, 1-deoxy-L-fructose, D-allose, L-glucose, L-talose, D-gulose, L-galactose, L-fucose, allitol, D-talitol, and L-sorbitol. New systems and robust catalysts resulting from advancements in genomics and bioengineering are also discussed.

  3. Biosynthesis of rare hexoses using microorganisms and related enzymes.

    Science.gov (United States)

    Li, Zijie; Gao, Yahui; Nakanishi, Hideki; Gao, Xiaodong; Cai, Li

    2013-11-12

    Rare sugars, referred to as monosaccharides and their derivatives that rarely exist in nature, can be applied in many areas ranging from foodstuffs to pharmaceutical and nutrition industry, or as starting materials for various natural products and drug candidates. Unfortunately, an important factor restricting the utilization of rare sugars is their limited availability, resulting from limited synthetic methods. Nowadays, microbial and enzymatic transformations have become a very powerful tool in this field. This article reviews the biosynthesis and enzymatic production of rare ketohexoses, aldohexoses and sugar alcohols (hexitols), including D-tagatose, D-psicose, D-sorbose, L-tagatose, L-fructose, 1-deoxy-L-fructose, D-allose, L-glucose, L-talose, D-gulose, L-galactose, L-fucose, allitol, D-talitol, and L-sorbitol. New systems and robust catalysts resulting from advancements in genomics and bioengineering are also discussed.

  4. Biosynthesis of polybrominated aromatic organic compounds by marine bacteria

    Science.gov (United States)

    Agarwal, Vinayak; El Gamal, Abrahim A.; Yamanaka, Kazuya; Poth, Dennis; Kersten, Roland D.; Schorn, Michelle; Allen, Eric E.; Moore, Bradley S.

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) and polybrominated bipyrroles are natural products that bioaccumulate in the marine food chain. PBDEs have attracted widespread attention due to their persistence in the environment and potential toxicity to humans. However, the natural origins of PBDE biosynthesis are not known. Here we report marine bacteria as producers of PBDEs and establish a genetic and molecular foundation for their production that unifies paradigms for the elaboration of bromophenols and bromopyrroles abundant in marine biota. We provide biochemical evidence of marine brominase enzymes revealing decarboxylative-halogenation enzymology previously unknown among halogenating enzymes. Biosynthetic motifs discovered in our study were used to mine sequence databases to discover unrealized marine bacterial producers of organobromine compounds. PMID:24974229

  5. Tyrosine biosynthesis, metabolism, and catabolism in plants.

    Science.gov (United States)

    Schenck, Craig A; Maeda, Hiroshi A

    2018-05-01

    L-Tyrosine (Tyr) is an aromatic amino acid (AAA) required for protein synthesis in all organisms, but synthesized de novo only in plants and microorganisms. In plants, Tyr also serves as a precursor of numerous specialized metabolites that have diverse physiological roles as electron carriers, antioxidants, attractants, and defense compounds. Some of these Tyr-derived plant natural products are also used in human medicine and nutrition (e.g. morphine and vitamin E). While the Tyr biosynthesis and catabolic pathways have been extensively studied in microbes and animals, respectively, those of plants have received much less attention until recently. Accumulating evidence suggest that the Tyr biosynthetic pathways differ between microbes and plants and even within the plant kingdom, likely to support the production of lineage-specific plant specialized metabolites derived from Tyr. The interspecies variations of plant Tyr pathway enzymes can now be used to enhance the production of Tyr and Tyr-derived compounds in plants and other synthetic biology platforms. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Ethanol production by recombinant and natural xylose-utilising yeasts

    Energy Technology Data Exchange (ETDEWEB)

    Eliasson, Anna

    2000-07-01

    The xylose-fermenting capacity of recombinant Saccharomyces cerevisiae carrying XYL1 and XYL2 from Pichia stipitis, which encode xylose reductase (XR) and xylitol dehydrogenase (XDH), respectively, is poor due to high xylitol formation. Whereas, P. stipitis exhibits high ethanol yield on xylose, the tolerance towards inhibitors in the lignocellulosic hydrolysate is low. A recombinant strain possessing the advantageous characteristics of both S. cerevisiae and P. stipitis would constitute a biocatalyst capable of efficient ethanol production from lignocellulosic hydrolysate. In the work presented in this thesis, factors influencing xylose fermentation in recombinant S. cerevisiae and in the natural xylose-fermenting yeast P. stipitis have been identified and investigated. Anaerobic xylulose fermentation was compared in strains of Zygosaccharomyces and S. cerevisiae, mutants and wild-type strains to identify host strain background and genetic modifications beneficial for xylose fermentation. The greatest positive effect was found for over-expression of the gene XKS1 for the pentose phosphate pathway (PPP) enzyme xylulokinase (XK), which increased the ethanol yield by almost 85%. The Zygosaccharomyces strains tested formed large amounts of polyols, making them unsuitable as host strains. The XR/XDH/XK ratio was found to determine whether carbon accumulated in a xylitol pool or was further utilised for ethanol production in recombinant xylose-utilising S. cerevisiae. Simulations, based on a kinetic model, and anaerobic xylose cultivation experiments implied that a 1:{>=}10:{>=}4 relation was optimal in minimising xylitol formation. Ethanol formation increased with decreasing XR/XDH ratio, whereas xylitol formation decreased and XK overexpression was necessary for adequate ethanol formation. Based on the knowledge of optimal enzyme ratios, a stable, xylose-utilising strain, S. cerevisiae TMB 3001, was constructed by chromosomal integration of the XYL1 and XYL2 genes

  7. Identification of potentially safe promising fungal cell factories for the production of polyketide natural food colorants using chemotaxonomic rationale

    Directory of Open Access Journals (Sweden)

    Frisvad Jens C

    2009-04-01

    Full Text Available Abstract Background Colorants derived from natural sources look set to overtake synthetic colorants in market value as manufacturers continue to meet the rising demand for clean label ingredients – particularly in food applications. Many ascomycetous fungi naturally synthesize and secrete pigments and thus provide readily available additional and/or alternative sources of natural colorants that are independent of agro-climatic conditions. With an appropriately selected fungus; using in particular chemotaxonomy as a guide, the fungal natural colorants could be produced in high yields by using the optimized cultivation technology. This approach could secure efficient production of pigments avoiding use of genetic manipulation. Results Polyketide pigment producing ascomycetous fungi were evaluated for their potential as production organisms based on a priori knowledge on species-specific pigment and potential mycotoxin production and BioSafety level (BSL classification. Based on taxonomic knowledge, we pre-selected ascomycetous fungi belonging to Penicillium subgenus Biverticillium that produced yellow, orange or red pigments while deselecting Penicillium marneffei; a well known human pathogen in addition to other mycotoxigenic fungi belonging to the same group. We identified 10 strains belonging to 4 species; viz. P. purpurogenum, P. aculeatum, P. funiculosum, and P. pinophilum as potential pigment producers that produced Monascus-like pigments but no known mycotoxins. The selection/deselection protocol was illustrated in the pigment extracts of P. aculeatum IBT 14259 and P. crateriforme IBT 5015 analysed by HPLC-DAD-MS. In addition, extracellular pigment producing ability of some of the potential pigment producers was evaluated in liquid media with a solid support and N-glutarylmonascorubramine was discovered in the partially purified pigment extract of P. purpurogenum IBT 11181 and IBT 3645. Conclusion The present work brought out that the use

  8. Deposits of naturally occurring radioactivity in production of oil and natural gas; Radioaktive avleiringer i olje- og gassproduksjon

    Energy Technology Data Exchange (ETDEWEB)

    Strand, T; Lysebo, I; Kristensen, D; Birovljev, A

    1997-01-01

    Deposits of naturally occurring radioactive materials is an increasing problem in Norwegian oil and gas production. Activity concentration in solid-state samples and production water, and doses to workers involved in different operations off-shore, have been measured. The report also includes a discussion of different methods of monitoring and alternatives for final disposal of wastes. 154 refs.

  9. High folate production by naturally occurring Lactobacillus sp. with ...

    African Journals Online (AJOL)

    African Journal of Biotechnology. Journal Home ... Milk products are good sources of such vitamins which are produced by probiotics. In order to ... Therefore, two new strains with an ability of high folate production were isolated and identified.

  10. On the nature of the new product strategy

    DEFF Research Database (Denmark)

    Larsson, Flemming

    2006-01-01

    The aim of this paper is to explore the concept of a new product strategy and its relation to portfolio management for product development. Based on a literature review this research adheres to one perception of the new product strategy proposed by literature complemented with a component adressing...... the risk-dimension. Next, it is suggested that the new product strategy is embedded in the product development strategy. Subsequently, it is advocated that companies try to achieve a base for realizing integration, synchronization and strategic alignment by means of a new product strategy. These three...... themes are explicated in a model, which also indicates the relation between the new product strategy and the product development process. Finally, implications for management practice are devised....

  11. Use of natural zeolite-supplemented litter increased broiler production

    African Journals Online (AJOL)

    smyo

    aimed at elucidating the effects of combinations of these products as litter on poultry production, such as .... The bulbs on the ceiling were used ... sample, curved fibrous and acicular mordenites were derived from volcanic glass (Figure 2b).

  12. Using Natural Products to Treat Resistant and Persistent Bacterial Infections

    Science.gov (United States)

    Deering, Robert W.

    Antimicrobial resistance is a growing threat to human health both worldwide and in the United States. Most concerning is the emergence of multi-drug resistant (MDR) bacterial pathogens, especially the 'ESKAPE' pathogens for which treatment options are dwindling. To complicate the problem, approvals of antibiotic drugs are extremely low and many research and development efforts in the pharmaceutical industry have ceased, leaving little certainty that critical new antibiotics are nearing the clinic. New antibiotics are needed to continue treating these evolving infections. In addition to antibiotics, approaches that aim to inhibit or prevent antimicrobial resistance could be useful. Also, studies that improve our understanding of bacterial pathophysiology could lead to new therapies for infectious disease. Natural products, especially those from the microbial world, have been invaluable as resources for new antibacterial compounds and as insights into bacterial physiology. The goal of this dissertation is to find new ways to treat resistant bacterial infections and learn more about the pathophysiology of these bacteria. Investigations of natural products to find molecules able to be used as new antibiotics or to modulate resistance and other parts of bacterial physiology are crucial aspects of the included studies. The first included study, which is reported in chapter two, details a chemical investigation of a marine Pseudoalteromonas sp. Purification efforts of the microbial metabolites were guided by testing against a resistance nodulation of cell division model of efflux pumps expressed in E. coli. These pumps play an important role in the resistance of MDR Gram negative pathogens such as Pseudomonas aeruginosa and Enterobacteriaceae. Through this process, 3,4-dibromopyrrole-2,5-dione was identified as a potent inhibitor of the RND efflux pumps and showed synergistic effects against the E. coli strain with common antibiotics including fluoroquinolones, beta

  13. Pilot Scale Production of Irradiated Natural Rubber Latex and its Dipping Products

    Directory of Open Access Journals (Sweden)

    M. Utama

    2005-07-01

    Full Text Available One hundred and fifty kg natural rubber latex (NRL before and after concentration were added with 3 phr (part hundred ratio of rubber normal butyl acrylate, then the mixture were irradiated at 25 kGy by gamma rays of 60Co in pilot scale. The irradiated natural rubber latex (INRL were then being to use for producing rubber products such as condom, surgical gloves, and spygmomanometer in factory scale. The quality of INRL and rubber products such as : total solid content (TSC, dry rubber content (DRC, KOH, VFA and MST number, tensile strength, modulus, elongation at break, extractable protein content, and response against Type I allergy etc. were evaluated. The economic aspect for producing INRL by means of Gamma Irradiator (GI and Electron Beam Machine (EBM such as payback period (PP, net present value (NPV and internal rate return (IRR were calculated. The results showed that the latex properties of INRL such as DRC, TSC, KOH, VFA, and MST number are not only found to the requirement of the ISO 2004 standard but also the latex has low protein, lipid, and carbohydrate content. The physical and mechanical properties (tensile strength, modulus, and elongation at break of rubber dipping products such as condom, gloves, and sphygmomanometer are not only found to the requirement of ISO 4074, ISO 10282, and ANSI/AAMI SP-1994 standards, but also the allergic response tested clinical latex-sensitive protein allergen by ELISA test on gloves, and by SPT test on condom are found to be negative. It indicates that production of INRL or PVNRL or RVNRL by EBM 250 keV/10 mA, was more cheap than by using gamma γ irradiator 200 kCi, or sulfur vulcanization. The value of PBP (payback period was 2,1 years, NPV (net present value was 4,250 US $, PI (profitability index 1,06 and IRR (internal rate of returns was 25,0%.

  14. Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production.

    Science.gov (United States)

    Liu, Xiaonan; Ding, Wentao; Jiang, Huifeng

    2017-07-19

    Plant natural products (PNPs) are widely used as pharmaceuticals, nutraceuticals, seasonings, pigments, etc., with a huge commercial value on the global market. However, most of these PNPs are still being extracted from plants. A resource-conserving and environment-friendly synthesis route for PNPs that utilizes microbial cell factories has attracted increasing attention since the 1940s. However, at the present only a handful of PNPs are being produced by microbial cell factories at an industrial scale, and there are still many challenges in their large-scale application. One of the challenges is that most biosynthetic pathways of PNPs are still unknown, which largely limits the number of candidate PNPs for heterologous microbial production. Another challenge is that the metabolic fluxes toward the target products in microbial hosts are often hindered by poor precursor supply, low catalytic activity of enzymes and obstructed product transport. Consequently, despite intensive studies on the metabolic engineering of microbial hosts, the fermentation costs of most heterologously produced PNPs are still too high for industrial-scale production. In this paper, we review several aspects of PNP production in microbial cell factories, including important design principles and recent progress in pathway mining and metabolic engineering. In addition, implemented cases of industrial-scale production of PNPs in microbial cell factories are also highlighted.

  15. Biosynthesis of tylophora alkaloids

    International Nuclear Information System (INIS)

    Mulchandani, N.B.; Iyer, S.S.; Badheka, L.P.

    1974-01-01

    Using labelled precursors, biosynthesis of the tylophora alkaloids, tylophorine, tylophorinidine and tylophorinide has been investigated in Tylophora asthmatica plants. The radioactive precursors, phenylalanine-2- 14 C, benzoic acid-1- 14 C, benzoic acid-ring 14 C, acetate-2- 14 C, ornithine-5- 14 C, acetate-2- 14 C, ornithine-5- 14 C and cinnamic acid-2- 14 C were administered to the plants individually by wick technique. Tylophorine was isolated in each case and assayed for its radioactivity to find out the incorporation of the label into it. The results indicate that: (1) phenylalanine via cinnamic acid is an important precursor in the biosynthesis of tylophorine (2) orinithine participates in tylophorine biosynthesis via pyrroline and (3) tylophorinidine may be a direct precursor of tylophorine. (M.G.B.)

  16. Natural personal care products-analysis of ingredient lists and legal situation.

    Science.gov (United States)

    Klaschka, Ursula

    2016-01-01

    Many natural substances are classified as dangerous substances according to the European regulation on classification and labelling. Are they used in natural personal care products today? One hundred ingredient lists were analyzed to find this out. All products with natural substances contained dangerous natural substances or they contained natural substances, for which the information about their classification as dangerous substances is not available. 54 natural substances quoted in the ingredient lists were found to be classified, with 37 substances being classified due to hazardous effects for skin and eyes. However, the most frequently used natural substances are not classified as dangerous. Natural substances are multi-constituent compounds, leading to two main problems in personal care products: the potential interactions of a multitude of substances and the fact that dangerous constituents are not disclosed in the ingredient lists. For example, the fragrance allergens citral, farnesol, limonene, and linalool are frequent components of the natural substances employed. In addition, 82 products listed allergenic fragrance ingredients as single substances in their ingredient lists. Recommendations for sensitive skin in a product's name do not imply that the '26 fragrance allergens' are omitted. Furthermore, 80 products listed 'parfum'/'aroma', and 50 products listed ethanol. The data show that the loopholes for natural substances and for personal care products in the present European chemical legislation (e.g. the exception for classification and labelling of cosmetic products and the exception for information transfer in the supply chain) are not in line with an adequate consumer and environmental protection.

  17. Comparative analysis of chemical similarity methods for modular natural products with a hypothetical structure enumeration algorithm.

    Science.gov (United States)

    Skinnider, Michael A; Dejong, Chris A; Franczak, Brian C; McNicholas, Paul D; Magarvey, Nathan A

    2017-08-16

    Natural products represent a prominent source of pharmaceutically and industrially important agents. Calculating the chemical similarity of two molecules is a central task in cheminformatics, with applications at multiple stages of the drug discovery pipeline. Quantifying the similarity of natural products is a particularly important problem, as the biological activities of these molecules have been extensively optimized by natural selection. The large and structurally complex scaffolds of natural products distinguish their physical and chemical properties from those of synthetic compounds. However, no analysis of the performance of existing methods for molecular similarity calculation specific to natural products has been reported to date. Here, we present LEMONS, an algorithm for the enumeration of hypothetical modular natural product structures. We leverage this algorithm to conduct a comparative analysis of molecular similarity methods within the unique chemical space occupied by modular natural products using controlled synthetic data, and comprehensively investigate the impact of diverse biosynthetic parameters on similarity search. We additionally investigate a recently described algorithm for natural product retrobiosynthesis and alignment, and find that when rule-based retrobiosynthesis can be applied, this approach outperforms conventional two-dimensional fingerprints, suggesting it may represent a valuable approach for the targeted exploration of natural product chemical space and microbial genome mining. Our open-source algorithm is an extensible method of enumerating hypothetical natural product structures with diverse potential applications in bioinformatics.

  18. Natural fibers for hydrogels production and their applications in agriculture

    Directory of Open Access Journals (Sweden)

    Liliana Serna Cock

    2017-10-01

    Full Text Available This paper presents a review on hydrogels applied to agriculture emphasizing on the use of natural fibers. The objectives were to examine, trends in research addressed to identify natural fibers used in hydrogels development and methods for modifying natural fibers, understand factors which determine the water retention capacity of a hydrogel. Consequently, this paper shows some methodologies used to evaluate the hydrogels efficiency and to collect in tables, relevant information in relation to methods of natural fibers modification and hydrogel synthesis. It was found that previous research focused on hydrogels development processed with biodegradable polymers such as starch, chitosan and modified natural fibers, cross-linked with potassium acrylate and acrylamide, respectively. In addition, current researches aimed to obtaining hydrogels with improved properties, which have allowed a resistance to climatic variations and soil physicochemical changes, such as pH, presence of salts, temperature and composition. In fact, natural fibers such as sugarcane, agave fiber and kapok fiber, modified with maleic anhydride, are an alternative to obtain hydrogels due to an increasing of mechanical properties and chemically active sites. However, the use of natural nanofibers in hydrogels, has been a successful proposal to improve hydrogels mechanical and swelling properties, since they give to material an elasticity and rigidity properties. A hydrogel efficiency applied to soil, is measured throughout properties as swellability, mechanical strength, and soil water retention. It was concluded that hydrogels, are an alternative to the current needs for the agricultural sector.

  19. Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening.

    Science.gov (United States)

    Lin, Shih-Hung; Huang, Kao-Jean; Weng, Ching-Feng; Shiuan, David

    2015-01-01

    Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR). The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank) database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity) properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration) values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening.

  20. Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.

    Science.gov (United States)

    Lee, M L; Schneider, G

    2001-01-01

    Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.

  1. Textbook for nature entrepreneurship : product of the WURKS project Nature Entrepreneurship and Tourism within Green Education (NatureToGo)

    NARCIS (Netherlands)

    Felder, M.; Pellis, A.

    2013-01-01

    In recent years, government funding for nature conservation and development has declined. As a result, links between nature conservation and entrepreneurship are increasingly being made in both practice and education. This comes with many questions and challenges. In Green Secondary Vocational

  2. New Concept of the Biosynthesis of 4-Alkyl-L-Proline Precursors of Lincomycin, Hormaomycin, and Pyrrolobenzodiazepines: Could a gamma-Glutamyltransferase Cleave the C-C Bond?

    Czech Academy of Sciences Publication Activity Database

    Jirásková, Petra; Gažák, Radek; Kameník, Zdeněk; Steiningerová, Lucie; Najmanová, Lucie; Kadlčík, Stanislav; Novotná, Jitka; Kuzma, Marek; Janata, Jiří

    2016-01-01

    Roč. 7, Mar 7 (2016), s. 276 ISSN 1664-302X R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) EE2.3.30.0003 Institutional support: RVO:61388971 Keywords : anticancer drug * antibiotics * natural product biosynthesis Subject RIV: EE - Microbiology, Virology Impact factor: 4.076, year: 2016

  3. Convergent Evolution of Ergothioneine Biosynthesis in Cyanobacteria.

    Science.gov (United States)

    Liao, Cangsong; Seebeck, Florian P

    2017-11-02

    Biosynthesis of N-α-trimethyl-2-thiohistidine (ergothioneine) is a frequent trait in cyanobacteria. This sulfur compound may provide essential relief from oxidative stress related to oxygenic photosynthesis. The central steps in ergothioneine biosynthesis are catalyzed by a histidine methyltransferase and an iron-dependent sulfoxide synthase. In this report, we present evidence that some cyanobacteria recruited and adapted a sulfoxide synthase from a different biosynthetic pathway to make ergothioneine. The discovery of a second origin of ergothioneine production underscores the physiological importance of this metabolite and highlights the evolutionary malleability of the thiohistidine biosynthetic machinery. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

    Science.gov (United States)

    Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

    2018-01-01

    The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

  5. Biosynthesis and function of chondroitin sulfate.

    Science.gov (United States)

    Mikami, Tadahisa; Kitagawa, Hiroshi

    2013-10-01

    Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions. Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo. Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes. Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Informatic search strategies to discover analogues and variants of natural product archetypes.

    Science.gov (United States)

    Johnston, Chad W; Connaty, Alex D; Skinnider, Michael A; Li, Yong; Grunwald, Alyssa; Wyatt, Morgan A; Kerr, Russell G; Magarvey, Nathan A

    2016-03-01

    Natural products are a crucial source of antimicrobial agents, but reliance on low-resolution bioactivity-guided approaches has led to diminishing interest in discovery programmes. Here, we demonstrate that two in-house automated informatic platforms can be used to target classes of biologically active natural products, specifically, peptaibols. We demonstrate that mass spectrometry-based informatic approaches can be used to detect natural products with high sensitivity, identifying desired agents present in complex microbial extracts. Using our specialised software packages, we could elaborate specific branches of chemical space, uncovering new variants of trichopolyn and demonstrating a way forward in mining natural products as a valuable source of potential pharmaceutical agents.

  7. Fatty Acid Biosynthesis Pathways in Methylomicrobium buryatense 5G(B1).

    Science.gov (United States)

    Demidenko, Aleksandr; Akberdin, Ilya R; Allemann, Marco; Allen, Eric E; Kalyuzhnaya, Marina G

    2016-01-01

    Methane utilization by methanotrophic bacteria is an attractive application for biotechnological conversion of natural or biogas into high-added-value products. Haloalcaliphilic methanotrophic bacteria belonging to the genus Methylomicrobium are among the most promising strains for methane-based biotechnology, providing easy and inexpensive cultivation, rapid growth, and the availability of established genetic tools. A number of methane bioconversions using these microbial cultures have been discussed, including the derivation of biodiesel, alkanes, and OMEGA-3 supplements. These compounds are derived from bacterial fatty acid pools. Here, we investigate fatty acid biosynthesis in Methylomicrobium buryatense 5G(B1) . Most of the genes homologous to typical Type II fatty acid biosynthesis pathways could be annotated by bioinformatics analyses, with the exception of fatty acid transport and regulatory elements. Different approaches for improving fatty acid accumulation were investigated. These studies indicated that both fatty acid degradation and acetyl- and malonyl-CoA levels are bottlenecks for higher level fatty acid production. The best strain generated in this study synthesizes 111 ± 2 mg/gDCW of extractable fatty acids, which is ~20% more than the original strain. A candidate gene for fatty acid biosynthesis regulation, farE , was identified and studied. Its deletion resulted in drastic changes to the fatty acid profile, leading to an increased pool of C18-fatty acid methyl ester. The FarE-regulon was further investigated by RNA-seq analysis of gene expression in farE -knockout mutants and farE -overexpressing strains. These gene profiles highlighted a novel set of enzymes and regulators involved in fatty acid biosynthesis. The gene expression and fatty acid profiles of the different farE -strains support the hypothesis that metabolic fluxes upstream of fatty acid biosynthesis restrict fatty acid production in the methanotroph.

  8. Contact heating of water products of combustion of natural gas

    Energy Technology Data Exchange (ETDEWEB)

    Aronov, I Z

    1978-01-01

    The USSR's NIIST examined the processes and equipment for heating water by submerged combustion using natural gas. Written for engineers involved with the design and application of thermal engineering equipment operating with natural gas, the book emphasizes equipment, test results, and methods of calculating heat transfer for contact gas economizers developed by Scientific Research Institute of Sanitary Engineering and other Soviet organizations. The economic effectiveness of submerged-combustion heating depends on several factors, including equipment design. Recommendations cover cost-effective designs and applications of contact economizers and boilers.

  9. Voracious transformation of a common natural resource into productive capital

    NARCIS (Netherlands)

    van der Ploeg, F.

    2010-01-01

    I analyze a power struggle where competing factions have private financial assets and deplete a common stock of natural resources with no private property rights. I obtain a feedback Nash equilibrium to the dynamic common-pool problem and obtain political variants of the Hotelling depletion rule and

  10. Use of natural zeolite-supplemented litter increased broiler production

    African Journals Online (AJOL)

    The aim of this study was to ascertain the influence of natural zeolite, consisting mainly of clinoptilolite and mordenite, as a component of the litter material in broiler houses on the performance of the broilers and on some litter characteristics. Live weight gain, feed consumption, feed efficiency, viability and leg and body ...

  11. Structural modeling of natural citrus products as potential cross ...

    African Journals Online (AJOL)

    There are four serotypes of Dengue virus and there are existing drugs used against specific serotype. There is no drug that is effective against all strains of this virus. In this research, bioinformatics tools were used to predict the affinity of natural ligands for the glycoprotein E of Dengue virus by considering the conserved ...

  12. Nature Relation Between Climatic Variables and Cotton Production

    Directory of Open Access Journals (Sweden)

    Zakaria M. Sawan

    2014-08-01

    Full Text Available This study investigated the effect of climatic variables on flower and boll production and retention in cotton (Gossypium barbadense. Also, this study investigated the relationship between climatic factors and production of flowers and bolls obtained during the development periods of the flowering and boll stage, and to determine the most representative period corresponding to the overall crop pattern. Evaporation, sunshine duration, relative humidity, surface soil temperature at 1800 h, and maximum air temperature, are the important climatic factors that significantly affect flower and boll production. The least important variables were found to be surface soil temperature at 0600 h and minimum temperature. There was a negative correlation between flower and boll production and either evaporation or sunshine duration, while that correlation with minimum relative humidity was positive. Higher minimum relative humidity, short period of sunshine duration, and low temperatures enhanced flower and boll formation.

  13. High folate production by naturally occurring Lactobacillus sp. with ...

    African Journals Online (AJOL)

    USER

    2010-08-16

    Aug 16, 2010 ... high folate production, isolation and identification of Lactobacilli in traditional fermented milk ... mended for pregnant women (Van Der Put et al., 2001; ...... utilization of folic acid and vitamin B12 by lactic cultures in skim milk.

  14. Natural Gas and Cellulosic Biomass: A Clean Fuel Combination? Determining the Natural Gas Blending Wall in Biofuel Production.

    Science.gov (United States)

    M Wright, Mark; Seifkar, Navid; Green, William H; Román-Leshkov, Yuriy

    2015-07-07

    Natural gas has the potential to increase the biofuel production output by combining gas- and biomass-to-liquids (GBTL) processes followed by naphtha and diesel fuel synthesis via Fischer-Tropsch (FT). This study reflects on the use of commercial-ready configurations of GBTL technologies and the environmental impact of enhancing biofuels with natural gas. The autothermal and steam-methane reforming processes for natural gas conversion and the gasification of biomass for FT fuel synthesis are modeled to estimate system well-to-wheel emissions and compare them to limits established by U.S. renewable fuel mandates. We show that natural gas can enhance FT biofuel production by reducing the need for water-gas shift (WGS) of biomass-derived syngas to achieve appropriate H2/CO ratios. Specifically, fuel yields are increased from less than 60 gallons per ton to over 100 gallons per ton with increasing natural gas input. However, GBTL facilities would need to limit natural gas use to less than 19.1% on a LHV energy basis (7.83 wt %) to avoid exceeding the emissions limits established by the Renewable Fuels Standard (RFS2) for clean, advanced biofuels. This effectively constitutes a blending limit that constrains the use of natural gas for enhancing the biomass-to-liquids (BTL) process.

  15. Production of mycotoxins on artificially and naturally infested building materials

    DEFF Research Database (Denmark)

    Nielsen, Kristian Fog; Gravesen, S.; Nielsen, P.A.

    1999-01-01

    , especially Asp. ustus and Asp. niger produced many unknown secondary metabolites on the building materials. Analyses of wallpaper and glass-fibre wallpaper naturally infested with Asp. versicolor revealed sterigmatocystin and 5-methoxysterigmatocystin. Analyses of naturally infested wallpaper showed that C......In this study, the ability to produce mycotoxins during growth on artificially infested building materials was investigated for Penicillium chrysogenum, Pen. polonicum, Pen. brevicompactum, Chaetomium spp., Aspergillus ustus, Asp. niger, Ulocladium spp., Alternaria spp., and Paecilomyces spp., all...... isolated from water-damaged building materials. Spores from the different isolates of the above mentioned species were inoculated on gypsum board with and without wallpaper and on chipboard with and without wallpaper. Fungal material was scraped off the materials, extracted, and analyzed using high...

  16. Improving Agricultural Productivity with Radiation Processed Natural Polymers

    International Nuclear Information System (INIS)

    Henriques, Sasha

    2013-01-01

    Full text: Through the power of irradiation to break and create chemical bonds, the natural polymer cassava starch is used to make super water absorbents (SWA), 1kg of which can absorb and hold 200 litres of water and release it slowly over time. Placed in the soil near plants’ roots, SWA can be used where there is little rain or frequent drought. After 9 months the crystals, which resemble sugar crystals, completely disintegrate, leaving no residue. (author)

  17. Application of natural and synthetic polymers in a production of paper

    Directory of Open Access Journals (Sweden)

    Jovanović Slobodan

    2007-01-01

    Full Text Available This work gives the review of most frequently used natural and synthetic polymers in production of paper, board and cardboard. Physical and chemical interaction of natural and synthetic polymers with cellulose fibers, and thus the way these polymers influence the improvement of both production process and the paper characteristics, have been presented.

  18. Natural Products Research in South Africa: End of an Era on Land or ...

    African Journals Online (AJOL)

    NICO

    single era of natural product chemistry research in South Africa but rather three ... The Specialization Era (ca. 1960–1990) ... South African Natural Products in the International Drug. Discovery .... subsequently proposed that 24 was formed through an initial ... complete elimination of M. grisea infestation by the commercial.

  19. Defining "natural product" between public health and business, 17th to 21st centuries.

    Science.gov (United States)

    Stanziani, Alessandro

    2008-07-01

    The historical definition of a natural product stands at the crossroads of business, health, and the symbolic order of things. Until the end of the 19th century, "natural product" was a synonym of perishable. The emergency of organic chemistry made perishability be replaced with "toxicity". Nowadays, genetics is provoking a radical change in the notion and practises of "natural product". However, these concerns are never entirely opposed to "naturality" as a synonym for sacred and symbolic order. Traceability is largely based upon kosher practices and the association between organic and good for health is hardly based upon sound scientific arguments.

  20. The encounter and analysis of naturally occurring radionuclides in gas and oil production and processing

    International Nuclear Information System (INIS)

    Hartog, F.A.; Jonkers, G.; Knaepen, W.A.I.

    1996-01-01

    As a result of oil and gas production, radioactive daughter elements from the uranium and thorium decay series can be mobilized and transported away from the reservoir. Due to changes in flow regime, temperature, pressure or chemical environment NORs (Naturally Occurring Radionuclides) may build up in products, by-products or waste streams from gas and oil production and processing facilities. Products containing NORs are commonly denoted by the acronym NORM (Naturally Occurring Radioactive Materials). Main topics of this paper are: E and P (Exploration and Production) NORM characteristics; incentives for NORM analysis; NORM analysis; interlaboratory test programme; analysis techniques; results and conclusions of the test programme. 4 figs., 2 tabs

  1. A balanced ATP driving force module for enhancing photosynthetic biosynthesis of 3-hydroxybutyrate from CO2.

    Science.gov (United States)

    Ku, Jason T; Lan, Ethan I

    2018-03-01

    Using engineered photoautotrophic microorganisms for the direct chemical synthesis from CO 2 is an attractive direction for both sustainability and CO 2 mitigation. However, the behaviors of non-native metabolic pathways may be difficult to control due to the different intracellular contexts between natural and heterologous hosts. While most metabolic engineering efforts focus on strengthening driving forces in pathway design to favor biochemical production in these organisms, excessive driving force may be detrimental to product biosynthesis due to imbalanced cellular intermediate distribution. In this study, an ATP-hydrolysis based driving force module was engineered into cyanobacterium Synechococcus elongatus PCC 7942 to produce 3-hydroxybutyrate (3HB), a valuable chemical feedstock for the synthesis of biodegradable plastics and antibiotics. However, while the ATP driving force module is effective for increasing product formation, uncontrolled accumulation of intermediate metabolites likely led to metabolic imbalance and thus to cell growth inhibition. Therefore, the ATP driving force module was reengineered by providing a reversible outlet for excessive carbon flux. Upon expression of this balanced ATP driving force module with 3HB biosynthesis, engineered strain produced 3HB with a cumulative titer of 1.2 g/L, a significant increase over the initial strain. This result highlighted the importance of pathway reversibility as an effective design strategy for balancing driving force and intermediate accumulation, thereby achieving a self-regulated control for increased net flux towards product biosynthesis. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  2. METHANOL PRODUCTION FROM BIOMASS AND NATURAL GAS AS TRANSPORTATION FUEL

    Science.gov (United States)

    Two processes are examined for production of methanol. They are assessed against the essential requirements of a future alternative fuel for road transport: that it (i) is producible in amounts comparable to the 19 EJ of motor fuel annually consumed in the U.S., (ii) minimizes em...

  3. Experience curve for natural gas production by hydraulic fracturing

    NARCIS (Netherlands)

    Fukui, R.; Greenfield, C.; Pogue, K.; van der Zwaan, B.

    From 2007 to 2012 shale gas production in the US expanded at an astounding average growth rate of over 50yr, and thereby increased nearly tenfold over this short time period alone. Hydraulic fracturing technology, or ``fracking'', as well as new directional drilling techniques, played key roles in

  4. Analysis of Specific Features of the Ukrainian Market of Natural Gas Production and Consumption

    Directory of Open Access Journals (Sweden)

    Lelyuk Oleksiy V.

    2013-11-01

    Full Text Available The article provides results of the study of specific features of the Ukrainian market of natural gas production and consumption. It analyses dynamics of the specific weight of Ukraine in general volumes of natural gas consumption in the world, dynamics of natural gas consumption in Ukraine during 1990 – 2012 and dependence of natural gas consumption on GDP volumes by the purchasing power parity. It studies the structure of natural gas consumption by regions in 2012 and sectors of economy, resource base of natural gas in Ukraine and also dynamics of established resources of natural gas in Ukraine and dynamics of natural gas production. It analyses base rates of growth of natural gas resources and production in Ukraine. It considers dynamics of import of natural gas into Ukraine and its import prices and also the structure of natural gas import. It identifies the balance of the natural gas market in Ukraine. On the basis of the conducted analysis the article proves that Ukraine is a gas-deficit country of the world, which depends on natural gas import supplies.

  5. Low-Molecular-Weight Metabolites from Diatoms: Structures, Biological Roles and Biosynthesis

    Directory of Open Access Journals (Sweden)

    Valentin Stonik

    2015-06-01

    Full Text Available Diatoms are abundant and important biological components of the marine environment that biosynthesize diverse natural products. These microalgae are rich in various lipids, carotenoids, sterols and isoprenoids, some of them containing toxins and other metabolites. Several groups of diatom natural products have attracted great interest due to their potential practical application as energy sources (biofuel, valuable food constituents, and prospective materials for nanotechnology. In addition, hydrocarbons, which are used in climate reconstruction, polyamines which participate in biomineralization, new apoptotic agents against tumor cells, attractants and deterrents that regulate the biochemical communications between marine species in seawaters have also been isolated from diatoms. However, chemical studies on these microalgae are complicated by difficulties, connected with obtaining their biomass, and the influence of nutrients and contaminators in their environment as well as by seasonal and climatic factors on the biosynthesis of the corresponding natural products. Overall, the number of chemically studied diatoms is lower than that of other algae, but further studies, particularly those connected with improvements in the isolation and structure elucidation technique as well as the genomics of diatoms, promise both to increase the number of studied species with isolated biologically active natural products and to provide a clearer perception of their biosynthesis.

  6. Exploring the production of natural gas through the lenses of the ACEGES model

    International Nuclear Information System (INIS)

    Voudouris, Vlasios; Matsumoto, Ken'ichi; Sedgwick, John; Rigby, Robert; Stasinopoulos, Dimitrios; Jefferson, Michael

    2014-01-01

    Due to the increasing importance of natural gas for modern economic activity, and gas's non-renewable nature, it is extremely important to try to estimate possible trajectories of future natural gas production while considering uncertainties in resource estimates, demand growth, production growth and other factors that might limit production. In this study, we develop future scenarios for natural gas supply using the ACEGES computational laboratory. Conditionally on the currently estimated ultimate recoverable resources, the ‘Collective View’ and ‘Golden Age’ Scenarios suggest that the supply of natural gas is likely to meet the increasing demand for natural gas until at least 2035. The ‘Golden Age’ Scenario suggests significant ‘jumps’ of natural gas production – important for testing the resilience of long-term strategies. - Highlights: • We present the ‘Collective View’ and ‘Golden Age’ Scenarios for natural gas production. • We do not observe any significant supply demand pressure of natural gas until 2035. • We do observe ‘jumps’ in natural gas supply until 2035. • The ACEGES-based scenarios can assess the resilience of longterm strategies

  7. Antiviral Activity of Natural Products Extracted from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Sobia Tabassum

    2011-11-01

    Full Text Available Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and pre-clinical stages. Marine compounds are paving the way for a new trend in modern medicine.

  8. Glycopeptide antibiotic biosynthesis.

    Science.gov (United States)

    Yim, Grace; Thaker, Maulik N; Koteva, Kalinka; Wright, Gerard

    2014-01-01

    Glycopeptides such as vancomycin, teicoplanin and telavancin are essential for treating infections caused by Gram-positive bacteria. Unfortunately, the dwindled pipeline of new antibiotics into the market and the emergence of glycopeptide-resistant enterococci and other resistant bacteria are increasingly making effective antibiotic treatment difficult. We have now learned a great deal about how bacteria produce antibiotics. This information can be exploited to develop the next generation of antimicrobials. The biosynthesis of glycopeptides via nonribosomal peptide assembly and unusual amino acid synthesis, crosslinking and tailoring enzymes gives rise to intricate chemical structures that target the bacterial cell wall. This review seeks to describe recent advances in our understanding of both biosynthesis and resistance of these important antibiotics.

  9. The utility of N-15 nuclear magnetic resonance spectroscopy for the study of natural products

    International Nuclear Information System (INIS)

    Randall, E.W.

    1978-01-01

    The utility of 15 N NMR spectroscopy for the study of natural products and the difficulties which must be overcome arte discussed. The widespread use of pulse Fourier techniques, decouplings, larger magnetic fields and large tube sizes allows a large number of 15 N studies of natural products, the more recent and important of these being peptides, nucleosides and nucleotides. Sites of protonation, tautomerism, sites of nitrosation and proton exchange behaviour for some of these natrual products have been studied. (A.G.)

  10. Engineering of a plasmid-free Escherichia coli strain for improved in vivo biosynthesis of astaxanthin

    Directory of Open Access Journals (Sweden)

    Steuer Kristin

    2011-04-01

    Full Text Available Abstract Background The xanthophyll astaxanthin is a high-value compound with applications in the nutraceutical, cosmetic, food, and animal feed industries. Besides chemical synthesis and extraction from naturally producing organisms like Haematococcus pluvialis, heterologous biosynthesis in non-carotenogenic microorganisms like Escherichia coli, is a promising alternative for sustainable production of natural astaxanthin. Recent achievements in the metabolic engineering of E. coli strains have led to a significant increase in the productivity of carotenoids like lycopene or β-carotene by increasing the metabolic flux towards the isoprenoid precursors. For the heterologous biosynthesis of astaxanthin in E. coli, however, the conversion of β-carotene to astaxanthin is obviously the most critical step towards an efficient biosynthesis of astaxanthin. Results Here we report the construction of the first plasmid-free E. coli strain that produces astaxanthin as the sole carotenoid compound with a yield of 1.4 mg/g cdw (E. coli BW-ASTA. This engineered E. coli strain harbors xanthophyll biosynthetic genes from Pantoea ananatis and Nostoc punctiforme as individual expression cassettes on the chromosome and is based on a β-carotene-producing strain (E. coli BW-CARO recently developed in our lab. E. coli BW-CARO has an enhanced biosynthesis of the isoprenoid precursor isopentenyl diphosphate (IPP and produces β-carotene in a concentration of 6.2 mg/g cdw. The expression of crtEBIY along with the β-carotene-ketolase gene crtW148 (NpF4798 and the β-carotene-hydroxylase gene (crtZ under controlled expression conditions in E. coli BW-ASTA directed the pathway exclusively towards the desired product astaxanthin (1.4 mg/g cdw. Conclusions By using the λ-Red recombineering technique, genes encoding for the astaxanthin biosynthesis pathway were stably integrated into the chromosome of E. coli. The expression levels of chromosomal integrated recombinant

  11. Patented installations for the production of methane and natural manures

    Energy Technology Data Exchange (ETDEWEB)

    Milquet, F

    1951-12-01

    Current processes are reviewed and a new technique is described which maintains economically a constant temperature of 40/sup 0/C in the tanks by complete isolation in winter as in summer and periodic reheating of the mass. The tanks were buried underground and had double metal walls with low density cellular concrete between them. The covers were of thick cork, permanently fixed, and coated with an impermeable substance. Reheating was necessary only once during the fermentation, whereas with tanks above ground it had to be carried out more often and more vigorously. Straw was the raw material and the products were highly profitable quantities of methane and artificial manure.

  12. Catalyst-controlled oligomerization for the collective synthesis of polypyrroloindoline natural products.

    Science.gov (United States)

    Jamison, Christopher R; Badillo, Joseph J; Lipshultz, Jeffrey M; Comito, Robert J; MacMillan, David W C

    2017-12-01

    In nature, many organisms generate large families of natural product metabolites that have related molecular structures as a means to increase functional diversity and gain an evolutionary advantage against competing systems within the same environment. One pathway commonly employed by living systems to generate these large classes of structurally related families is oligomerization, wherein a series of enzymatically catalysed reactions is employed to generate secondary metabolites by iteratively appending monomers to a growing serial oligomer chain. The polypyrroloindolines are an interesting class of oligomeric natural products that consist of multiple cyclotryptamine subunits. Herein we describe an iterative application of asymmetric copper catalysis towards the synthesis of six distinct oligomeric polypyrroloindoline natural products: hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given the customizable nature of the small-molecule catalysts employed, we demonstrate that this strategy is further amenable to the construction of quadrigemine H-type alkaloids not isolated previously from natural sources.

  13. Insects: an underrepresented resource for the discovery of biologically active natural products

    Directory of Open Access Journals (Sweden)

    Lauren Seabrooks

    2017-07-01

    Full Text Available Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.

  14. Sustainability, natural and organic cosmetics: consumer, products, efficacy, toxicological and regulatory considerations

    Directory of Open Access Journals (Sweden)

    Bruno Fonseca-Santos

    2015-03-01

    Full Text Available The interest in sustainable products has increased along the years, since the choice of products, packaging and production processes have a great impact on the environment. These products are classified by regulatory agencies in different categories, aggregating advantages to the product and increasing the demand by consumers. However, there is no harmonization in guidelines of these certifying agencies and each cosmetic industry formulates their product and packaging in a more rational way, which causes less damage to the environment. Many cosmetic products have in their formulation natural products that perform a specific biological function, but these products should be evaluated on efficacy and toxicological aspects. The aim of this article is to approach sustainability, natural and organic cosmetics, considering the consumer and the efficacy, toxicological and regulatory aspects.

  15. Management of natural health products in pediatrics: a provider-focused quality improvement project.

    Science.gov (United States)

    Gutierrez, Emily; Silbert-Flagg, JoAnne; Vohra, Sunita

    2015-01-01

    The use of natural health products by pediatric patients is common, yet health care providers often do not provide management guidance. The purpose of this project was to improve management of natural health products by pediatric nurse practitioners. Pediatric nurse practitioners from large metropolitan city were recruited (n = 32). A paired pretest-posttest design was used. Study participants were engaged to improve knowledge of natural health products, and a management toolkit was created and tested. Mean knowledge scores increased from 59.19 to 76.3 (p improved with regard to patient guidance (p product use (p = .51) and drug/herb interactions (p = .35) were not significant. This investigation is the first known study to improve knowledge and management of natural health products in pediatric clinical practice. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  16. Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

    Science.gov (United States)

    Zha, Weibin

    2018-04-01

    The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

  17. Application of phase-trafficking methods to natural products research.

    Science.gov (United States)

    Araya, Juan J; Montenegro, Gloria; Mitscher, Lester A; Timmermann, Barbara N

    2010-09-24

    A novel simultaneous phase-trafficking approach using spatially separated solid-supported reagents for rapid separation of neutral, basic, and acidic compounds from organic plant extracts with minimum labor is reported. Acidic and basic ion-exchange resins were physically separated into individual sacks ("tea bags") for trapping basic and acidic compounds, respectively, leaving behind in solution neutral components of the natural mixtures. Trapped compounds were then recovered from solid phase by appropriate suspension in acidic or basic solutions. The feasibility of the proposed separation protocol was demonstrated and optimized with an "artificial mixture" of model compounds. In addition, the utility of this methodology was illustrated with the successful separation of the alkaloid skytanthine from Skytanthus acutus Meyen and the main catechins and caffeine from Camellia sinensis L. (Kuntze). This novel approach offers multiple advantages over traditional extraction methods, as it is not labor intensive, makes use of only small quantities of solvents, produces fractions in adequate quantities for biological assays, and can be easily adapted to field conditions for bioprospecting activities.

  18. Natural Products for the Treatment of Trachoma and Chlamydia trachomatis

    Directory of Open Access Journals (Sweden)

    Michael G. Potroz

    2015-03-01

    Full Text Available The neglected tropical disease (NTD trachoma is currently the leading cause of eye disease in the world, and the pathogenic bacteria causing this condition, Chlamydia trachomatis, is also the most common sexually transmitted pathogenic bacterium. Although the serovars of this bacterial species typically vary between ocular and genital infections there is a clear connection between genital C. trachomatis infections and the development of trachoma in infants, such that the solutions to these infections are closely related. It is the unique life cycle of the C. trachomatis bacteria which primarily leads to chronic infections and challenges in treatment using conventional antibiotics. This life cycle involves stages of infective elementary bodies (EBs and reproductive reticulate bodies (RBs. Most antibiotics only target the reproductive RBs and this often leads to the need for prolonged therapy which facilitates the development of drug resistant pathogens. It is through combining several compounds to obtain multiple antimicrobial mechanisms that we are most likely to develop a reliable means to address all these issues. Traditional and ethnobotanical medicine provides valuable resources for the development of novel formulations and treatment regimes based on synergistic and multi-compound therapy. In this review we intend to summarize the existing literature on the application of natural compounds for controlling trachoma and inhibiting chlamydial bacteria and explore the potential for the development of new treatment modalities.

  19. NMR structural studies of oligosaccharides and other natural products

    DEFF Research Database (Denmark)

    Kjærulff, Louise

    produce secondary metabolites for signaling and competing against other organisms, and these molecules are important in drug discovery due to their inherent biological activities. From a marine Photobacterium (P. halotolerans) we isolated the solonamides and the ngercheumicins, two families of cyclic...... through the nJCH correlation, this experiment has exciting applications for configurational assignment of e.g. carbohydrates and for residual dipolar couplings. Identification of known molecules and discovery of novel molecules are other important applications of NMR spectroscopy. Bacteria and fungi....... fijiensis, was also investigated for production of novel secondary metabolites, and a new pyranonigrin (E) was isolated and structure elucidated by NMR spectroscopy along with JBIR-74 and decumbenone A, two known metabolites previously isolated from Aspergillus and Penicillium species. Oligosaccharides...

  20. Exploring fungal biodiversity for the production of water-soluble pigments as potential natural food colorants

    DEFF Research Database (Denmark)

    Mapari, Sameer Shamsuddin; Nielsen, Kristian Fog; Larsen, Thomas Ostenfeld

    2005-01-01

    The production of many currently authorized natural food colorants has a number of disadvantages, including a dependence on the supply of raw materials and variations in pigment extraction. Fungi provide a readily available alternative source of naturally derived food colorants that could easily...... be produced in high yields. The recent authorization of a fungal food colorant has fuelled research to explore the extraordinary chemical diversity and biodiversity of fungi for the biotechnological production of pigments as natural food colorants. These studies require an appropriate use of chernotaxonomic...... technology, in the future it should be possible to employ metabolic engineering to create microbial cell factories for the production of food colorants....

  1. Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms.

    Science.gov (United States)

    Büschleb, Martin; Dorich, Stéphane; Hanessian, Stephen; Tao, Daniel; Schenthal, Kyle B; Overman, Larry E

    2016-03-18

    Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quaternary carbon atoms in their intricate structures are reviewed with 12 representative examples. Emphasis has been put on methods to create quaternary carbon stereocenters, including syntheses of the same natural product by different groups, thereby showcasing the diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quaternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. NATURAL PRODUCTS AS PRESERVATIVES FOR FAST GROWTH WOODS - A REVIEW

    Directory of Open Access Journals (Sweden)

    Ricardo Marques Barreiros

    2011-11-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabela normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Wood is a universal material, economic, historic and sustainable. The paucity of species resistant to biological degradation forced man to use other less durable, especially fast growing, from reforestation, as some species of Eucalyptus and Pinus. These species have moderate or no resistance to wood decay organisms need special treatment and preservatives. The products currently used preservatives are highly toxic and are potential environmental hazards and human health. Thus, there is a growing need to develop effective chemicals, non-toxic to humans and the environment. The direction of research has aimed to develop environmentally friendly products and economic viability, and an alternative is the use of Crude Tall Oil (CTO, which is a waste processing coniferous softwood pulp for the production of kraft paper. The tall oil as a protective agent, has been considered a promising method for significantly reducing the capillary water absorption of sapwood, thereby removing one of the factors that favor the wood being attacked by fungi and insects: water, oxygen and nutrients. Research shows that the tall oil can be used neat, either fresh or distilled, or in combination with biocides.A madeira é um material universal, econ

  3. Natural products for chronic cough: Text mining the East Asian historical literature for future therapeutics.

    Science.gov (United States)

    Shergis, Johannah Linda; Wu, Lei; May, Brian H; Zhang, Anthony Lin; Guo, Xinfeng; Lu, Chuanjian; Xue, Charlie Changli

    2015-08-01

    Chronic cough is a significant health burden. Patients experience variable benefits from over the counter and prescribed products, but there is an unmet need to provide more effective treatments. Natural products have been used to treat cough and some plant compounds such as pseudoephedrine from ephedra and codeine from opium poppy have been developed into drugs. Text mining historical literature may offer new insight for future therapeutic development. We identified natural products used in the East Asian historical literature to treat chronic cough. Evaluation of the historical literature revealed 331 natural products used to treat chronic cough. Products included plants, minerals and animal substances. These natural products were found in 75 different books published between AD 363 and 1911. Of the 331 products, the 10 most frequently and continually used products were examined, taking into consideration findings from contemporary experimental studies. The natural products identified are promising and offer new directions in therapeutic development for treating chronic cough. © The Author(s) 2015.

  4. EFFECTS OF OIL AND NATURAL GAS PRICES ON INDUSTRIAL PRODUCTION IN THE EUROZONE MEMBER COUNTRIES

    Directory of Open Access Journals (Sweden)

    Yılmaz BAYAR

    2014-04-01

    Full Text Available Industrial production is one of the leading indicators of gross domestic product which reflects the overall economic performance of a country. In other words decreases or increases in industrial production point out a contracting or expanding economy. Therefore, changes in prices of oil and natural gas which are the crucial inputs to the industrial production are also important for the overall economy. This study examines the effects of changes in oil and natural gas prices on the industrial production in the 18 Eurozone member countries during the period January 2001-September 2013 by using panel regression. We found that oil prices and natural gas prices had negative effect on industrial production in the Eurozone member countries.

  5. Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening

    Directory of Open Access Journals (Sweden)

    Lin SH

    2015-06-01

    Full Text Available Shih-Hung Lin,1 Kao-Jean Huang,1,2 Ching-Feng Weng,1 David Shiuan1 1Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 2Development Center of Biotechnology, Taipei, Taiwan, Republic of China Abstract: Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR. The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening. Keywords: HMG-CoA reductase, virtual screening, curcumin, salvianolic acid C

  6. Products of steel slags an opportunity to save natural resources.

    Science.gov (United States)

    Motz, H; Geiseler, J

    2001-01-01

    already accepted as a CEN standard and are used for a continuous quality control. Usually the suitability of steel slags is stated by fulfilling the requirements of national and/or international standards and regulations. Based on these standards and regulations in Germany in 1998 about 97% of the produced steel slags have been used as aggregates for road construction (e.g. as surface layer, road base and sub base for high trafficked roads), ways, earthworks, and armourstones for hydraulic structures. Consistent to the successful long-term experience not only products of steel slags but also products of blast furnace slags have been eliminated from the European Waste Catalogue and the European Shipment of Waste Regulation of the European Community, as well as from the lists of OECD for transfrontier movements by the decision of the OECD-Council from 21 September, 1995.

  7. Soil Properties and Plant Biomass Production in Natural Rangeland Management Systems

    Directory of Open Access Journals (Sweden)

    Romeu de Souza Werner

    Full Text Available ABSTRACT Improper management of rangelands can cause land degradation and reduce the economic efficiency of livestock activity. The aim of this study was to evaluate soil properties and quantify plant biomass production in four natural rangeland management systems in the Santa Catarina Plateau (Planalto Catarinense of Brazil. The treatments, which included mowed natural rangeland (NR, burned natural rangeland (BR, natural rangeland improved through the introduction of plant species after harrowing (IH, and natural rangeland improved through the introduction of plant species after chisel plowing (IC, were evaluated in a Nitossolo Bruno (Nitisol. In the improved treatments, soil acidity was corrected, phosphate fertilizer was applied, and intercropped annual ryegrass (Lolium multiflorum, velvet grass (Holcus lanatus, and white clover (Trifolium repens were sown. Management systems with harrowed or chisel plowed soil showed improved soil physical properties; however, the effect decreased over time and values approached those of burned and mowed natural rangelands. Natural rangeland systems in the establishment phase had little influence on soil organic C. The mowed natural rangeland and improved natural rangeland exhibited greater production of grazing material, while burning the field decreased production and increased the proportion of weeds. Improvement of the natural rangelands increased leguminous biomass for pasture.

  8. Importance of microbial natural products and the need to revitalize their discovery.

    Science.gov (United States)

    Demain, Arnold L

    2014-02-01

    Microbes are the leading producers of useful natural products. Natural products from microbes and plants make excellent drugs. Significant portions of the microbial genomes are devoted to production of these useful secondary metabolites. A single microbe can make a number of secondary metabolites, as high as 50 compounds. The most useful products include antibiotics, anticancer agents, immunosuppressants, but products for many other applications, e.g., antivirals, anthelmintics, enzyme inhibitors, nutraceuticals, polymers, surfactants, bioherbicides, and vaccines have been commercialized. Unfortunately, due to the decrease in natural product discovery efforts, drug discovery has decreased in the past 20 years. The reasons include excessive costs for clinical trials, too short a window before the products become generics, difficulty in discovery of antibiotics against resistant organisms, and short treatment times by patients for products such as antibiotics. Despite these difficulties, technology to discover new drugs has advanced, e.g., combinatorial chemistry of natural product scaffolds, discoveries in biodiversity, genome mining, and systems biology. Of great help would be government extension of the time before products become generic.

  9. Investigation on natural radioactive nuclide contents of rock products in Xi'an construction materials market

    International Nuclear Information System (INIS)

    Zhou Chunlin; Han Feng; Shang Aiguo; Li Tiantuo; Guo Huiping; Yie Lichao; Li Guifang

    2001-01-01

    The author reports the investigation results on natural radioactive nuclide contents of rock products from Xi'an construction materials market. The products were classified according to the national standard. The results show that natural radioactive nuclide contents in sampled rock products are in normal radioactive background levels. The radio-activity ranges of 238 U, 226 Ra, 232 Th and 40 K are 2.7 - 181.8, 0.92 - 271.0, 0.63 - 148.0, 1.8 - 1245 Bq·kg -1 , respectively. According to the national standard (JC 518-93), the application of some rock products must be limited

  10. Expanding Canadian natural gas production will strengthen growth of LP-gas industry

    International Nuclear Information System (INIS)

    Hawkins, D.J.

    1994-01-01

    In 1992, over 86% of Canadian propane and 70% of Canadian butane production originated in gas plants. Propane and butane production not recovered at gas plants is recovered in other processing facilities, primarily refineries and heavy oil upgraders. As a result, supplies of both products are largely tied to natural gas production, and the outlook for natural gas therefore provides the basis for any discussion on the outlook for gas processing and NGL industry infrastructure. The paper discusses gas processing, economies of scale, NGL supply, expected declines, industry structure and infrastructure, the two major centers of the Canadian NGL industry, new shippers, and required pipeline expansion

  11. Cyclic Sulfamidate Enabled Syntheses of Amino Acids, Peptides, Carbohydrates, and Natural Products

    Science.gov (United States)

    This article reviews the emergence of cyclic sulfamidates as versatile intermediatesfor the synthesis of unnatural amino acids, chalcogen peptides, modified sugars, drugs and drug candidates, and important natural products.

  12. Evaluation of natural products as potential agrochemical agents with insecticide, fungicide and herbicide activities

    CSIR Research Space (South Africa)

    Dumontet, V

    2012-07-01

    Full Text Available The present work aims to identify new promising plant sources, which could be exploited for their agrochemical properties. A total of 484 natural products from academic libraries were selected for screening against four fungal pathogens, five...

  13. Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction.

    Science.gov (United States)

    Woerly, Eric M; Roy, Jahnabi; Burke, Martin D

    2014-06-01

    The inherent modularity of polypeptides, oligonucleotides and oligosaccharides has been harnessed to achieve generalized synthesis platforms. Importantly, like these other targets, most small-molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled both the synthesis of a wide range of polyene frameworks that covered all of this natural-product chemical space and the first total syntheses of the polyene natural products asnipyrone B, physarigin A and neurosporaxanthin b-D-glucopyranoside. Collectively, these results suggest the potential for a more generalized approach to making small molecules in the laboratory.

  14. Synthesis of most polyene natural product motifs using just twelve building blocks and one coupling reaction

    Science.gov (United States)

    Woerly, Eric M.; Roy, Jahnabi; Burke, Martin D.

    2014-01-01

    The inherent modularity of polypeptides, oligonucleotides, and oligosaccharides has been harnessed to achieve generalized building block-based synthesis platforms. Importantly, like these other targets, most small molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled the synthesis of a wide range of polyene frameworks covering all of this natural product chemical space, and first total syntheses of the polyene natural products asnipyrone B, physarigin A, and neurosporaxanthin β-D-glucopyranoside. Collectively, these results suggest the potential for a more generalized approach for making small molecules in the laboratory. PMID:24848233

  15. Design of compound libraries based on natural product scaffolds and protein structure similarity clustering (PSSC)

    NARCIS (Netherlands)

    Balamurugan, Rengarajan; Dekker, Frank J; Waldmann, Herbert; Dekker, Frans

    Recent advances in structural biology, bioinformatics and combinatorial chemistry have significantly impacted the discovery of small molecules that modulate protein functions. Natural products which have evolved to bind to proteins may serve as biologically validated starting points for the design

  16. Inhibition of aflatoxin B production of Aspergillus flavus, isolated from soybean seeds by certain natural plant products.

    Science.gov (United States)

    Krishnamurthy, Y L; Shashikala, J

    2006-11-01

    The inhibitory effect of cowdung fumes, Captan, leaf powder of Withania somnifera, Hyptis suaveolens, Eucalyptus citriodora, peel powder of Citrus sinensis, Citrus medica and Punica granatum, neem cake and pongamia cake and spore suspension of Trichoderma harzianum and Aspergillus niger on aflatoxin B(1) production by toxigenic strain of Aspergillus flavus isolated from soybean seeds was investigated. Soybean seed was treated with different natural products and fungicide captan and was inoculated with toxigenic strain of A. flavus and incubated for different periods. The results showed that all the treatments were effective in controlling aflatoxin B(1) production. Captan, neem cake, spore suspension of T. harzianum, A. niger and combination of both reduced the level of aflatoxin B(1) to a great extent. Leaf powder of W. somnifera, H. suaveolens, peel powder of C. sinensis, C. medica and pongamia cake also controlled the aflatoxin B(1) production. All the natural product treatments applied were significantly effective in inhibiting aflatoxin B(1) production on soybean seeds by A. flavus. These natural plant products may successfully replace chemical fungicides and provide an alternative method to protect soybean and other agricultural commodities from aflatoxin B(1) production by A. flavus.

  17. Evaluation of antioxidant activity of natural products; Kosanka seibun no kino hyokaho

    Energy Technology Data Exchange (ETDEWEB)

    Miyazawa, T.; Nakagawa, K. [Tohoku Univ., Sendai (Japan)

    1998-10-20

    The methods for evaluating antioxidant property of natural products in in vitro and in vivo lipid peroxidation systems are reviewed. Antioxidant activity of tocopherols, carotenoids, flavonoids and curcuminoids have been demonstrated against lipid peroxidation induced in microsomes, erythrocytes, plasma lipoproteins and in animal trials. Recently, in vivo antioxidant function of natural products was extensively investigated in humans together with explanation of their absorbability and metabolic fate. 35 refs., 8 figs., 4 tabs.

  18. Study on preparation of new antioxidants for radiation vulcanized natural rubber latex product. Antioxidant from keratin

    International Nuclear Information System (INIS)

    Nguyen Quoc Hien; Nguyen Van Toan; Vo Tan Thien; Le Hai

    2000-01-01

    The thermo-oxidative aging resistance of radiation vulcanization of natural rubber latex (RVNRL) products should be adequately by using suitable antioxidants or new kind of effective antioxidant. This work presents the results of preparation of natural antioxidant from hair keratin. Characteristics and effectiveness of resultant antioxidant are also presented. The results obtained indicates that antioxidant made from hair keratin is safe and effective for rubber products from RVNRL. (author)

  19. Collision-Induced Dissociation Mass Spectrometry: A Powerful Tool for Natural Product Structure Elucidation.

    Science.gov (United States)

    Johnson, Andrew R; Carlson, Erin E

    2015-11-03

    Mass spectrometry is a powerful tool in natural product structure elucidation, but our ability to directly correlate fragmentation spectra to these structures lags far behind similar efforts in peptide sequencing and proteomics. Often, manual data interpretation is required and our knowledge of the expected fragmentation patterns for many scaffolds is limited, further complicating analysis. Here, we summarize advances in natural product structure elucidation based upon the application of collision induced dissociation fragmentation mechanisms.

  20. Tolerance of natural baby skin-care products on healthy, full-term infants and toddlers

    OpenAIRE

    Coret, Catherine D; Suero, Michael B; Tierney, Neena K

    2014-01-01

    Catherine D Coret, Michael B Suero, Neena K Tierney Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, USA Purpose: To evaluate the tolerance of baby skin-care products with at least 95% naturally derived ingredients on infants and toddlers. Materials and methods: Healthy, full-term infants and toddlers aged 1–36 months were enrolled. In study 1, a lightly fragranced natural baby hair and body wash (n=30), a lightly fragranced natural baby shampoo (n=30), or a lightly...

  1. Recent Advances in Substrate-Controlled Asymmetric Cyclization for Natural Product Synthesis

    Directory of Open Access Journals (Sweden)

    Jeyun Jo

    2017-06-01

    Full Text Available Asymmetric synthesis of naturally occurring diverse ring systems is an ongoing and challenging research topic. A large variety of remarkable reactions utilizing chiral substrates, auxiliaries, reagents, and catalysts have been intensively investigated. This review specifically describes recent advances in successful asymmetric cyclization reactions to generate cyclic architectures of various natural products in a substrate-controlled manner.

  2. De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.

    Science.gov (United States)

    Eichenberger, Michael; Hansson, Anders; Fischer, David; Dürr, Lara; Naesby, Michael

    2018-06-01

    Anthocyanins (ACNs) are plant secondary metabolites responsible for most of the red, purple and blue colors of flowers, fruits and vegetables. They are increasingly used in the food and beverage industry as natural alternative to artificial colorants. Production of these compounds by fermentation of microorganisms would provide an attractive alternative. In this study, Saccharomyces cerevisiae was engineered for de novo production of the three basic anthocyanins, as well as the three main trans-flavan-3-ols. Enzymes from different plant sources were screened and efficient variants found for most steps of the biosynthetic pathway. However, the anthocyanidin synthase was identified as a major obstacle to efficient production. In yeast, this enzyme converts the majority of its natural substrates leucoanthocyanidins into the off-pathway flavonols. Nonetheless, de novo biosynthesis of ACNs was shown for the first time in yeast and for the first time in a single microorganism. It provides a framework for optimizing the activity of anthocyanidin synthase and represents an important step towards sustainable industrial production of these highly relevant molecules in yeast.

  3. Occurrence and biosynthesis of carotenoids in phytoplankton.

    Science.gov (United States)

    Huang, Jim Junhui; Lin, Shaoling; Xu, Wenwen; Cheung, Peter Chi Keung

    2017-09-01

    Naturally occurring carotenoids are important sources of antioxidants, anti-cancer compounds and anti-inflammatory agents and there is thus considerable market demand for their pharmaceutical applications. Carotenoids are widely distributed in marine and freshwater organisms including microalgae, phytoplankton, crustaceans and fish, as well as in terrestrial plants and birds. Recently, phytoplankton-derived carotenoids have received much attention due to their abundance, rapid rate of biosynthesis and unique composition. The carotenoids that accumulate in particular phytoplankton phyla are synthesized by specific enzymes and play unique physiological roles. This review focuses on studies related to the occurrence of carotenoids in different phytoplankton phyla and the molecular aspects of their biosynthesis. Recent biotechnological advances in the isolation and characterization of some representative carotenoid synthases in phytoplankton are also discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Magnesium affects rubber biosynthesis and particle stability in Ficus elastica, Hevea brasiliensis and Parthenium argentatum

    Science.gov (United States)

    Natural rubber biosynthesis occurs in laticifers of Ficus elastica and Hevea brasiliensis, and in parenchyma cells of Parthenium argentatum. Natural rubber is synthesized by rubber transferase using allylic pyrophosphates as initiators, isopentenyl pyrophosphate as monomeric substrate and magnesium ...

  5.  Mutations of noncollagen genes in osteogenesis imperfecta – implications of the gene products in collagen biosynthesis and pathogenesis of disease

    Directory of Open Access Journals (Sweden)

    Anna Galicka

    2012-06-01

    Full Text Available  Recent investigations revealed that the “brittle bone” phenotype in osteogenesis imperfecta (OI is caused not only by dominant mutations in collagen type I genes, but also by recessively inherited mutations in genes responsible for the post-translational processing of type I procollagen as well as for bone formation. The phenotype of patients with mutations in noncollagen genes overlaps with very severe type III and lethal type II OI caused by mutations in collagen genes. Mutations in genes that encode proteins involved in collagen prolyl 3-hydroxylation (P3H1/CRTAP/CyPB eliminated Pro986 hydroxylation and caused an increase in modification of collagen helix by prolyl 4-hydroxylase and lysyl hydroxylase. However, the importance of these disturbances in the disease pathomechanism is not known. Loss of complex proteins’ function as collagen chaperones may dominate the disease mechanism. The latest findings added to the spectrum of OI-causing and collagen-influencing factors other chaperones (HSP47 and FKBP65 and protein BMP-1, which emphasizes the complexity of collagen folding and secretion as well as their importance in bone formation. Furthermore, mutations in genes encoding transcription factor SP7/Osterix and pigment epithelium-derived factor (PEDF constitute a novel mechanism for OI, which is independent of changes in biosynthesis and processing of collagen.

  6. (1,3;1,4)-β-Glucan Biosynthesis by the CSLF6 Enzyme: Position and Flexibility of Catalytic Residues Influence Product Fine Structure.

    Science.gov (United States)

    Dimitroff, George; Little, Alan; Lahnstein, Jelle; Schwerdt, Julian G; Srivastava, Vaibhav; Bulone, Vincent; Burton, Rachel A; Fincher, Geoffrey B

    2016-04-05

    Cellulose synthase-like F6 (CslF6) genes encode polysaccharide synthases responsible for (1,3;1,4)-β-glucan biosynthesis in cereal grains. However, it is not clear how both (1,3)- and (1,4)-linkages are incorporated into a single polysaccharide chain and how the frequency and arrangement of the two linkage types that define the fine structure of the polysaccharide are controlled. Through transient expression in Nicotiana benthamiana leaves, two CSLF6 orthologs from different cereal species were shown to mediate the synthesis of (1,3;1,4)-β-glucans with very different fine structures. Chimeric cDNA constructs with interchanged sections of the barley and sorghum CslF6 genes were developed to identify regions of the synthase enzyme responsible for these differences. A single amino acid residue upstream of the TED motif in the catalytic region was shown to dramatically change the fine structure of the polysaccharide produced. The structural basis of this effect can be rationalized by reference to a homology model of the enzyme and appears to be related to the position and flexibility of the TED motif in the active site of the enzyme. The region and amino acid residue identified provide opportunities to manipulate the solubility of (1,3;1,4)-β-glucan in grains and vegetative tissues of the grasses and, in particular, to enhance the solubility of dietary fibers that are beneficial to human health.

  7. Regulatory cross-talks and cascades in rice hormone biosynthesis pathways contribute to stress signaling

    Directory of Open Access Journals (Sweden)

    Arindam Deb

    2016-08-01

    Full Text Available Crosstalk among different hormone signaling pathways play an important role in modulating plant response to both biotic and abiotic stress. Hormone activity is controlled by its bio-availability, which is again influenced by its biosynthesis. Thus independent hormone biosynthesis pathways must be regulated and co-ordinated to mount an integrated response. One of the possibilities is to use cis-regulatory elements to orchestrate expression of hormone biosynthesis genes. Analysis of CREs, associated with differentially expressed hormone biosynthesis related genes in rice leaf under Magnaporthe oryzae attack and drought stress enabled us to obtain insights about cross-talk among hormone biosynthesis pathways at the transcriptional level. We identified some master transcription regulators that co-ordinate different hormone biosynthesis pathways under stress. We found that Abscisic acid and Brassinosteroid regulate Cytokinin conjugation; conversely Brassinosteroid biosynthesis is affected by both Abscisic acid and Cytokinin. Jasmonic acid and Ethylene biosynthesis may be modulated by Abscisic acid through DREB transcription factors. Jasmonic acid or Salicylic acid biosynthesis pathways are co-regulated but they are unlikely to influence each other’s production directly. Thus multiple hormones may modulate hormone biosynthesis pathways through a complex regulatory network, where biosynthesis of one hormone is affected by several other contributing hormones.

  8. Influence of natural organic matter fouling and osmotic backwash on pressure retarded osmosis energy production from natural salinity gradients.

    Science.gov (United States)

    Yip, Ngai Yin; Elimelech, Menachem

    2013-01-01

    Pressure retarded osmosis (PRO) has the potential to produce clean, renewable energy from natural salinity gradients. However, membrane fouling can lead to diminished water flux productivity, thus reducing the extractable energy. This study investigates organic fouling and osmotic backwash cleaning in PRO and the resulting impact on projected power generation. Fabricated thin-film composite membranes were fouled with model river water containing natural organic matter. The water permeation carried foulants from the feed river water into the membrane porous support layer and caused severe water flux decline of ∼46%. Analysis of the water flux behavior revealed three phases in membrane support layer fouling. Initial foulants of the first fouling phase quickly adsorbed at the active-support layer interface and caused a significantly greater increase in hydraulic resistance than the subsequent second and third phase foulants. The water permeability of the fouled membranes was lowered by ∼39%, causing ∼26% decrease in projected power density. A brief, chemical-free osmotic backwash was demonstrated to be effective in removing foulants from the porous support layer, achieving ∼44% recovery in projected power density. The substantial performance recovery after cleaning was attributed to the partial restoration of the membrane water permeability. This study shows that membrane fouling detrimentally impacts energy production, and highlights the potential strategies to mitigate fouling in PRO power generation with natural salinity gradients.

  9. Diversity of governance arrangements for indigenous natural products in communal areas of Namibia

    NARCIS (Netherlands)

    Ndeinoma, A.; Wiersum, K.F.

    2017-01-01

    In several countries, it has been observed that development of policies and regulations for non-timber forest products (NTFPs) rarely follows a systematic approach. This paper characterises the diversity of governance arrangements for accessing and marketing indigenous natural products in communal

  10. Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis.

    Science.gov (United States)

    Hotta, Kinya; Chen, Xi; Paton, Robert S; Minami, Atsushi; Li, Hao; Swaminathan, Kunchithapadam; Mathews, Irimpan I; Watanabe, Kenji; Oikawa, Hideaki; Houk, Kendall N; Kim, Chu-Young

    2012-03-04

    Polycyclic polyether natural products have fascinated chemists and biologists alike owing to their useful biological activity, highly complex structure and intriguing biosynthetic mechanisms. Following the original proposal for the polyepoxide origin of lasalocid and isolasalocid and the experimental determination of the origins of the oxygen and carbon atoms of both lasalocid and monensin, a unified stereochemical model for the biosynthesis of polyether ionophore antibiotics was proposed. The model was based on a cascade of nucleophilic ring closures of postulated polyepoxide substrates generated by stereospecific oxidation of all-trans polyene polyketide intermediates. Shortly thereafter, a related model was proposed for the biogenesis of marine ladder toxins, involving a series of nominally disfavoured anti-Baldwin, endo-tet epoxide-ring-opening reactions. Recently, we identified Lsd19 from the Streptomyces lasaliensis gene cluster as the epoxide hydrolase responsible for the epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A. Here we report the X-ray crystal structure of Lsd19 in complex with its substrate and product analogue to provide the first atomic structure-to our knowledge-of a natural enzyme capable of catalysing the disfavoured epoxide-opening cyclic ether formation. On the basis of our structural and computational studies, we propose a general mechanism for the enzymatic catalysis of polyether natural product biosynthesis. © 2012 Macmillan Publishers Limited. All rights reserved

  11. Natural radiation - a perspective to radiological risk factors of nuclear energy production

    DEFF Research Database (Denmark)

    Mustonen, R.; Christensen, T.; Stranden, E.

    1992-01-01

    Radiation doses from natural radiation and from man-made modifications on natural radiation, and different natural radiological environments in the Nordic countries are summarized and used as a perspective for the radiological consequences of nuclear energy production. The significance of different...... radiation sources can be judged against the total collective effective dose equivalent from natural radiation in the Nordic countries, 92 000 manSv per year. The collective dose from nuclear energy production during normal operation is estimated to 20 manSv per year and from non-nuclear energy production...... to 80 manSv per year. The increase in collective dose due to the conservation of heating energy in Nordic dwellings is estimated to 23 000 manSv per year, from 1973 to 1984. An indirect radiological danger index is defined in order to be able to compare the significance of estimated future releases...

  12. Regional air quality impacts of increased natural gas production and use in Texas.

    Science.gov (United States)

    Pacsi, Adam P; Alhajeri, Nawaf S; Zavala-Araiza, Daniel; Webster, Mort D; Allen, David T

    2013-04-02

    Natural gas use in electricity generation in Texas was estimated, for gas prices ranging from $1.89 to $7.74 per MMBTU, using an optimal power flow model. Hourly estimates of electricity generation, for individual electricity generation units, from the model were used to estimate spatially resolved hourly emissions from electricity generation. Emissions from natural gas production activities in the Barnett Shale region were also estimated, with emissions scaled up or down to match demand in electricity generation as natural gas prices changed. As natural gas use increased, emissions decreased from electricity generation and increased from natural gas production. Overall, NOx and SO2 emissions decreased, while VOC emissions increased as natural gas use increased. To assess the effects of these changes in emissions on ozone and particulate matter concentrations, spatially and temporally resolved emissions were used in a month-long photochemical modeling episode. Over the month-long photochemical modeling episode, decreases in natural gas prices typical of those experienced from 2006 to 2012 led to net regional decreases in ozone (0.2-0.7 ppb) and fine particulate matter (PM) (0.1-0.7 μg/m(3)). Changes in PM were predominantly due to changes in regional PM sulfate formation. Changes in regional PM and ozone formation are primarily due to decreases in emissions from electricity generation. Increases in emissions from increased natural gas production were offset by decreasing emissions from electricity generation for all the scenarios considered.

  13. In-use product stocks link manufactured capital to natural capital.

    Science.gov (United States)

    Chen, Wei-Qiang; Graedel, T E

    2015-05-19

    In-use stock of a product is the amount of the product in active use. In-use product stocks provide various functions or services on which we rely in our daily work and lives, and the concept of in-use product stock for industrial ecologists is similar to the concept of net manufactured capital stock for economists. This study estimates historical physical in-use stocks of 91 products and 9 product groups and uses monetary data on net capital stocks of 56 products to either approximate or compare with in-use stocks of the corresponding products in the United States. Findings include the following: (i) The development of new products and the buildup of their in-use stocks result in the increase in variety of in-use product stocks and of manufactured capital; (ii) substitution among products providing similar or identical functions reflects the improvement in quality of in-use product stocks and of manufactured capital; and (iii) the historical evolution of stocks of the 156 products or product groups in absolute, per capita, or per-household terms shows that stocks of most products have reached or are approaching an upper limit. Because the buildup, renewal, renovation, maintenance, and operation of in-use product stocks drive the anthropogenic cycles of materials that are used to produce products and that originate from natural capital, the determination of in-use product stocks together with modeling of anthropogenic material cycles provides an analytic perspective on the material linkage between manufactured capital and natural capital.

  14. Hydrogen Production by Steam Reforming of Natural Gas Over Vanadium-Nickel-Alumina Catalysts.

    Science.gov (United States)

    Yoo, Jaekyeong; Park, Seungwon; Song, Ji Hwan; Song, In Kyu

    2018-09-01

    A series of vanadium-nickel-alumina (xVNA) catalysts were prepared by a single-step sol-gel method with a variation of vanadium content (x, wt%) for use in the hydrogen production by steam reforming of natural gas. The effect of vanadium content on the physicochemical properties and catalytic activities of xVNA catalysts in the steam reforming of natural gas was investigated. It was found that natural gas conversion and hydrogen yield showed volcano-shaped trends with respect to vanadium content. It was also revealed that natural gas conversion and hydrogen yield increased with decreasing nickel crystallite size.

  15. Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced Genome Editing.

    Science.gov (United States)

    Weber, Jakob; Valiante, Vito; Nødvig, Christina S; Mattern, Derek J; Slotkowski, Rebecca A; Mortensen, Uffe H; Brakhage, Axel A

    2017-01-20

    Filamentous fungi produce varieties of natural products even in a strain dependent manner. However, the genetic basis of chemical speciation between strains is still widely unknown. One example is trypacidin, a natural product of the opportunistic human pathogen Aspergillus fumigatus, which is not produced among different isolates. Combining computational analysis with targeted gene editing, we could link a single nucleotide insertion in the polyketide synthase of the trypacidin biosynthetic pathway and reconstitute its production in a nonproducing strain. Thus, we present a CRISPR/Cas9-based tool for advanced molecular genetic studies in filamentous fungi, exploiting selectable markers separated from the edited locus.

  16. Discovery and characterization of natural products that act as pheromones in fish.

    Science.gov (United States)

    Li, Ke; Buchinger, Tyler J; Li, Weiming

    2018-06-20

    Covering: up to 2018 Fish use a diverse collection of molecules to communicate with conspecifics. Since Karlson and Lüscher termed these molecules 'pheromones', chemists and biologists have joined efforts to characterize their structures and functions. In particular, the understanding of insect pheromones developed at a rapid pace, set, in part, by the use of bioassay-guided fractionation and natural product chemistry. Research on vertebrate pheromones, however, has progressed more slowly. Initially, biologists characterized fish pheromones by screening commercially available compounds suspected to act as pheromones based upon their physiological function. Such biology-driven screening has proven a productive approach to studying pheromones in fish. However, the many functions of fish pheromones and diverse metabolites that fish release make predicting pheromone identity difficult and necessitate approaches led by chemistry. Indeed, the few cases in which pheromone identification was led by natural product chemistry indicated novel or otherwise unpredicted compounds act as pheromones. Here, we provide a brief review of the approaches to identifying pheromones, placing particular emphasis on the promise of using natural product chemistry together with assays of biological activity. Several case studies illustrate bioassay-guided fractionation as an approach to pheromone identification in fish and the unexpected diversity of pheromone structures discovered by natural product chemistry. With recent advances in natural product chemistry, bioassay-guided fractionation is likely to unveil an even broader collection of pheromone structures and enable research that spans across disciplines.

  17. Marine actinobacteria associated with marine organisms and their potentials in producing pharmaceutical natural products.

    Science.gov (United States)

    Valliappan, Karuppiah; Sun, Wei; Li, Zhiyong

    2014-09-01

    Actinobacteria are ubiquitous in the marine environment, playing an important ecological role in the recycling of refractory biomaterials and producing novel natural products with pharmic applications. Actinobacteria have been detected or isolated from the marine creatures such as sponges, corals, mollusks, ascidians, seaweeds, and seagrass. Marine organism-associated actinobacterial 16S rRNA gene sequences, i.e., 3,003 sequences, deposited in the NCBI database clearly revealed enormous numbers of actinobacteria associated with marine organisms. For example, RDP classification of these sequences showed that 112 and 62 actinobacterial genera were associated with the sponges and corals, respectively. In most cases, it is expected that these actinobacteria protect the host against pathogens by producing bioactive compounds. Natural products investigation and functional gene screening of the actinobacteria associated with the marine organisms revealed that they can synthesize numerous natural products including polyketides, isoprenoids, phenazines, peptides, indolocarbazoles, sterols, and others. These compounds showed anticancer, antimicrobial, antiparasitic, neurological, antioxidant, and anti-HIV activities. Therefore, marine organism-associated actinobacteria represent an important resource for marine drugs. It is an upcoming field of research to search for novel actinobacteria and pharmaceutical natural products from actinobacteria associated with the marine organisms. In this review, we attempt to summarize the present knowledge on the diversity and natural products production of actinobacteria associated with the marine organisms, based on the publications from 1991 to 2013.

  18. Metabolic Engineering of the Actinomycete Amycolatopsis sp. Strain ATCC 39116 towards Enhanced Production of Natural Vanillin

    OpenAIRE

    Fleige, Christian; Meyer, Florian; Steinbüchel, Alexander

    2016-01-01

    The Gram-positive bacterium Amycolatopsis sp. ATCC 39116 is used for the fermentative production of natural vanillin from ferulic acid on an industrial scale. The strain is known for its outstanding tolerance to this toxic product. In order to improve the productivity of the fermentation process, the strain's metabolism was engineered for higher final concentrations and molar yields. Degradation of vanillin could be decreased by more than 90% through deletion of the vdh gene, which codes for ...

  19. Natural gas productive capacity for the lower 48 states, 1982--1993

    International Nuclear Information System (INIS)

    1993-01-01

    The purpose of this report is to analyze monthly natural gas wellhead productive capacity and project this capacity for 1992 and 1993, based upon historical production data through 1991. Productive capacity is the volume of gas that can be produced from a well, reservoir, or field during a given period of time against a certain wellhead back-pressure under actual reservoir conditions excluding restrictions imposed by pipeline capacity, contracts, or regulatory bodies. For decades, natural gas supplies and productive capacity have been adequate, although in the 1970's the capacity surplus was small because of market structure (both interstate and intrastate), increasing demand, and insufficient drilling. In the early 1980's, lower demand together with increased drilling led to a large surplus of natural gas capacity. After 1986, this large surplus began to decline as demand for gas increased, gas prices dropped, and gas well completions dropped sharply. In late December 1989, this surplus decline, accompanied by exceptionally high demand and temporary weather-related production losses, led to concerns about the adequacy of monthly productive capacity for natural gas. This study indicates that monthly productive capacity will drop sharply during the 1992-1993 period. In the low gas price, low drilling case, gas productive capacity and estimated production demand will be roughly equal in December 1993. In base and high drilling cases, monthly productive capacity should be able to meet normal production demands through 1993 in the lower 48 States. Exceptionally high peak-day or peak-week production demand might not be met because of physical limitations. Beyond 1993, as the capacity of currently producing wells declines, a sufficient number of wells and/or imports must be added each year in order to ensure an adequate gas supply

  20. Chiral thiazoline and thiazole building blocks for the synthesis of peptide-derived natural products.

    Science.gov (United States)

    Just-Baringo, Xavier; Albericio, Fernando; Alvarez, Mercedes

    2014-01-01

    Thiazoline and thiazole heterocycles are privileged motifs found in numerous peptide-derived natural products of biological interest. During the last decades, the synthesis of optically pure building blocks has been addressed by numerous groups, which have developed a plethora of strategies to that end. Efficient and reliable methodologies that are compatible with the intricate and capricious architectures of natural products are a must to further develop their science. Structure confirmation, structure-activity relationship studies and industrial production are fields of paramount importance that require these robust methodologies in order to successfully bring natural products into the clinic. Today's chemist toolbox is assorted with many powerful methods for chiral thiazoline and thiazole synthesis. Ranging from biomimetic approaches to stereoselective alkylations, one is likely to find a suitable method for their needs.

  1. Microbial production of natural gas from coal and organic-rich shale

    Science.gov (United States)

    Orem, William

    2013-01-01

    Natural gas is an important component of the energy mix in the United States, producing greater energy yield per unit weight and less pollution compared to coal and oil. Most of the world’s natural gas resource is thermogenic, produced in the geologic environment over time by high temperature and pressure within deposits of oil, coal, and shale. About 20 percent of the natural gas resource, however, is produced by microorganisms (microbes). Microbes potentially could be used to generate economic quantities of natural gas from otherwise unexploitable coal and shale deposits, from coal and shale from which natural gas has already been recovered, and from waste material such as coal slurry. Little is known, however, about the microbial production of natural gas from coal and shale.

  2. Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.

    Science.gov (United States)

    Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio

    2014-07-01

    Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.

  3. Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute Configuration Assignment.

    Science.gov (United States)

    N L Batista, Andrea; M Dos Santos, Fernando; Batista, João M; Cass, Quezia B

    2018-02-23

    Chiral natural product molecules are generally assumed to be biosynthesized in an enantiomerically pure or enriched fashion. Nevertheless, a significant amount of racemates or enantiomerically enriched mixtures has been reported from natural sources. This number is estimated to be even larger since the enantiomeric purity of secondary metabolites is rarely checked in the natural product isolation pipeline. This latter fact may have drastic effects on the evaluation of the biological activity of chiral natural products. A second bottleneck is the determination of their absolute configurations. Despite the widespread use of optical rotation and electronic circular dichroism, most of the stereochemical assignments are based on empirical correlations with similar compounds reported in the literature. As an alternative, the combination of vibrational circular dichroism and quantum chemical calculations has emerged as a powerful and reliable tool for both conformational and configurational analysis of natural products, even for those lacking UV-Vis chromophores. In this review, we aim to provide the reader with a critical overview of the occurrence of enantiomeric mixtures of secondary metabolites in nature as well the best practices for their detection, enantioselective separation using liquid chromatography, and determination of absolute configuration by means of vibrational circular dichroism and density functional theory calculations.

  4. Mutants of Streptomyces coeruleorubidus impaired in the biosynthesis of daunomycinone glycosides and related metabolites

    International Nuclear Information System (INIS)

    Blumauerova, M.; Stajner, K.; Pokorny, V.; Hostalek, Z.; Vanek, Z.

    1978-01-01

    Mutants of Streptomyces coeruleorubidus, blocked in the biosynthesis of anthracycline antibiotics of the daunomycine complex, were isolated from the production strains after treatment with UV light, γ-radiation, nitrous acid, and after natural selection; according to their different biosynthetic activity the mutants were divided into five phenotypic groups. Mutants of two of these groups produced compounds that had not yet been described in Streptomyces coeruleorubidus (aklavinone, 7-deoxyaklavinone, zeta-rhodomycinone and glycosides of epsilon-rhodomycinone). The mutants differed from the parent strains and also mutually in morphological characteristics but no direct correlation between these changes and the biosynthetic activity could be observed in most cases. (author)

  5. Natural products from Cuscuta reflexa Roxb. with antiproliferation activities in HCT116 colorectal cell lines.

    Science.gov (United States)

    Riaz, Muhammad; Bilal, Aishah; Ali, Muhammad Shaiq; Fatima, Itrat; Faisal, Amir; Sherkheli, Muhammad Azhar; Asghar, Adnan

    2017-03-01

    Parasitic Cuscuta reflexa Roxb. possesses many medicinal properties and is a rich source of a variety of biologically relevant natural products. Natural products are the prime source of leads, drugs, and drug templates, and many of the anticancer and antiviral drugs are either based on natural product or derived from them. Cancer is a devastating disease and one of the leading causes of death worldwide despite improvements in patient survival during the past 50 years; new and improved treatments for cancer are therefore actively sought. Colorectal cancer is the fourth most prevalent cancer worldwide and is responsible for nearly 9% of all cancer deaths. Our search for anticancer natural products from C. reflexa has yielded four natural products: Scoparone (1), p-coumaric acid (2), stigmasta-3,5-diene (3) and 1-O-p-hydroxycinnamoylglucose (4) and among them 1-O-p-hydroxycinnamoyldlucose (4) showed promising antiproliferative activities in HCT116 colorectal cell lines, whereas compounds 1-3 showed moderate activities.

  6. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    Science.gov (United States)

    Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

    2016-10-01

    Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Epoxide hydrolase Lsd19 for polyether formation in the biosynthesis of lasalocid A: direct experimental evidence on polyene-polyepoxide hypothesis in polyether biosynthesis.

    Science.gov (United States)

    Shichijo, Yoshihiro; Migita, Akira; Oguri, Hiroki; Watanabe, Mami; Tokiwano, Tetsuo; Watanabe, Kenji; Oikawa, Hideaki

    2008-09-17

    Polyether metabolites are an important class of natural products. Although their biosynthesis, especially construction of polyether skeletons, attracted organic chemists for many years, no experimental data on the enzymatic polyether formation has been obtained. In this study, a putative epoxide hydrolase gene lsd19 found on the biosynthetic gene cluster of an ionophore polyether lasalocid was cloned and successfully overexpressed in Escherichia coli. Using the purified Lsd19, a proposed substrate, bisepoxyprelasalocid, and its synthesized analogue were successfully converted into lasalocid A and its derivative via a 6-endo-tet cyclization mode. On the other hand, treatment of the bisepoxide with trichloroacetic acid gave isolasalocid A via a 5-exo-tet cyclization mode. Therefore, the enzymatic conversion observed in this study unambiguously showed that the bisepoxyprelasalocid is an intermediate of the lasalocid biosynthesis and that Lsd19 catalyzes the sequential cyclic ether formations involving an energetically disfavored 6-endo-tet cyclization. This is the first example of the enzymatic epoxide-opening reactions leading to a polyether natural product.

  8. Monoterpene biosynthesis potential of plant subcellular compartments.

    Science.gov (United States)

    Dong, Lemeng; Jongedijk, Esmer; Bouwmeester, Harro; Van Der Krol, Alexander

    2016-01-01

    Subcellular monoterpene biosynthesis capacity based on local geranyl diphosphate (GDP) availability or locally boosted GDP production was determined for plastids, cytosol and mitochondria. A geraniol synthase (GES) was targeted to plastids, cytosol, or mitochondria. Transient expression in Nicotiana benthamiana indicated local GDP availability for each compartment but resulted in different product levels. A GDP synthase from Picea abies (PaGDPS1) was shown to boost GDP production. PaGDPS1 was also targeted to plastids, cytosol or mitochondria and PaGDPS1 and GES were coexpressed in all possible combinations. Geraniol and geraniol-derived products were analyzed by GC-MS and LC-MS, respectively. GES product levels were highest for plastid-targeted GES, followed by mitochondrial- and then cytosolic-targeted GES. For each compartment local boosting of GDP biosynthesis increased GES product levels. GDP exchange between compartments is not equal: while no GDP is exchanged from the cytosol to the plastids, 100% of GDP in mitochondria can be exchanged to plastids, while only 7% of GDP from plastids is available for mitochondria. This suggests a direct exchange mechanism for GDP between plastids and mitochondria. Cytosolic PaGDPS1 competes with plastidial GES activity, suggesting an effective drain of isopentenyl diphosphate from the plastids to the cytosol. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  9. Medicinal plants and natural products in amelioration of arsenic toxicity: a short review.

    Science.gov (United States)

    Bhattacharya, Sanjib

    2017-12-01

    Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis. To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically. Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies. This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.

  10. An assessment of natural product discovery from marine (sensu strictu) and marine-derived fungi

    Science.gov (United States)

    Overy, David P.; Bayman, Paul; Kerr, Russell G.; Bills, Gerald F.

    2014-01-01

    The natural products community has been investigating secondary metabolites from marine fungi for several decades, but when one attempts to search for validated reports of new natural products from marine fungi, one encounters a literature saturated with reports from ‘marine-derived’ fungi. Of the 1000+ metabolites that have been characterized to date, only approximately 80 of these have been isolated from species from exclusively marine lineages. These metabolites are summarized here along with the lifestyle and habitats of their producing organisms. Furthermore, we address some of the reasons for the apparent disconnect between the stated objectives of discovering new chemistry from marine organisms and the apparent neglect of the truly exceptional obligate marine fungi. We also offer suggestions on how to reinvigorate enthusiasm for marine natural products discovery from fungi from exclusive marine lineages and highlight the need for critically assessing the role of apparently terrestrial fungi in the marine environment. PMID:25379338

  11. An introduction to planar chromatography and its application to natural products isolation.

    Science.gov (United States)

    Gibbons, Simon

    2012-01-01

    Thin-layer chromatography (TLC) is an easy, inexpensive, rapid, and the most widely used method for the analysis and isolation of small organic natural and synthetic products. It also has use in the biological evaluation of organic compounds, particularly in the areas of antimicrobial and antioxidant metabolites and for the evaluation of acetylcholinesterase inhibitors which have utility in the treatment of Alzheimer's disease. The ease and inexpensiveness of use of this technique, coupled with the ability to rapidly develop separation and bioassay protocols will ensure that TLC will be used for some considerable time alongside conventional instrumental methods. This chapter deals with the basic principles of TLC and describes methods for the analysis and isolation of natural products. Examples of methods for isolation of several classes of natural product are detailed and protocols for TLC bioassays are given.

  12. Natural antifouling compound production by microbes associated with marine macroorganisms — A review

    Directory of Open Access Journals (Sweden)

    Sathianeson Satheesh

    2016-05-01

    Full Text Available In the marine environment, all hard surfaces including marine macroorganims are colonized by microorganisms mainly from the surrounding environment. The microorganisms associated with marine macroorganisms offer tremendous potential for exploitation of bioactive metabolites. Biofouling is a continuous problem in marine sectors which needs huge economy for control and cleaning processes. Biotechnological way for searching natural product antifouling compounds gained momentum in recent years because of the environmental pollution associated with the use of toxic chemicals to control biofouling. While, natural product based antifoulants from marine organisms particularly sponges and corals attained significance due to their activities in field assays, collection of larger amount of organisms from the sea is not a viable one. The microorganisms associated with sponges, corals, ascidians, seaweeds and seagrasses showed strong antimicrobial and also antifouling activities. This review highlights the advances in natural product antifoulants research from microbes associated with marine organisms.

  13. Biosynthesis of flavonoids in bilberry and blueberry - possibilities of the gene level information for the future

    OpenAIRE

    Jaakola, Laura

    2007-01-01

    We have studied the biosynthesis of flavonoids in various tissues of naturally growing European blueberry (bilberry) and the blueberry cultivar 'Northblue'. Focus has also been on the biosynthesis of flavonoids in developing bilberry fruits as well as on the control genes regulating fruit development.

  14. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ginkel, Paul R. van; Yan, Michael B. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Bhattacharya, Saswati [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Pediatrics, University of Wisconsin, Madison, WI 53792 (United States); Polans, Arthur S., E-mail: aspolans@wisc.edu [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Kenealey, Jason D. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT 84602 (United States)

    2015-11-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP{sub 3} pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca{sup 2+}-dependent pro-apoptotic pathways inhibit cancer cell growth.

  15. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    International Nuclear Information System (INIS)

    Ginkel, Paul R. van; Yan, Michael B.; Bhattacharya, Saswati; Polans, Arthur S.; Kenealey, Jason D.

    2015-01-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP 3 pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca 2+ -dependent pro-apoptotic pathways inhibit cancer cell growth.

  16. Natural gas productive capacity for the lower 48 states 1984 through 1996, February 1996

    International Nuclear Information System (INIS)

    1996-01-01

    This is the fourth wellhead productive capacity report. The three previous ones were published in 1991, 1993, and 1994. This report should be of particular interest to those in Congress, Federal and State agencies, industry, and the academic community, who are concerned with the future availability of natural gas. The EIA Dallas Field Office has prepared five earlier reports regarding natural gas productive capacity. These reports, Gas Deliverability and Flow Capacity of Surveillance Fields, reported deliverability and capacity data for selected gas fields in major gas producing areas. The data in the reports were based on gas-well back-pressure tests and estimates of gas-in-place for each field or reservoir. These reports use proven well testing theory, most of which has been employed by industry since 1936 when the Bureau of Mines first published Monograph 7. Demand for natural gas in the United States is met by a combination of natural gas production, underground gas storage, imported gas, and supplemental gaseous fuels. Natural gas production requirements in the lower 48 States have been increasing during the last few years while drilling has remained at low levels. This has raised some concern about the adequacy of future gas supplies, especially in periods of peak heating or cooling demand. The purpose of this report is to address these concerns by presenting a 3-year projection of the total productive capacity of natural gas at the wellhead for the lower 48 States. Alaska is excluded because Alaskan gas does not enter the lower-48 States pipeline system. The Energy Information Administration (EIA) generates this 3-year projection based on historical gas-well drilling and production data from State, Federal, and private sources. In addition to conventional gas-well gas, coalbed gas and oil-well gas are also included

  17. Natural gas productive capacity for the lower 48 States, 1980 through 1995

    International Nuclear Information System (INIS)

    1994-01-01

    The purpose of this report is to analyze monthly natural gas wellhead productive capacity in the lower 48 States from 1980 through 1992 and project this capacity from 1993 through 1995. For decades, natural gas supplies and productive capacity have been adequate to meet demand. In the 1970's the capacity surplus was small because of market structure (split between interstate and intrastate), increasing demand, and insufficient drilling. In the early 1980's, lower demand, together with increased drilling, led to a large surplus capacity as new productive capacity came on line. After 1986, this large surplus began to decline as demand for gas increased, gas prices fell, and gas well completions dropped sharply. In late December 1989, the decline in this surplus, accompanied by exceptionally high demand and temporary weather-related production losses, led to concerns about the adequacy of monthly productive capacity for natural gas. These concerns should have been moderated by the gas system's performance during the unusually severe winter weather in March 1993 and January 1994. The declining trend in wellhead productive capacity is expected to be reversed in 1994 if natural gas prices and drilling meet or exceed the base case assumption. This study indicates that in the low, base, and high drilling cases, monthly productive capacity should be able to meet normal production demands through 1995 in the lower 48 States (Figure ES1). Exceptionally high peak-day or peak-week production demand might not be met because of physical limitations such as pipeline capacity. Beyond 1995, as the capacity of currently producing wells declines, a sufficient number of wells and/or imports must be added each year in order to ensure an adequate gas supply

  18. Natural Fostering in Fritillaria cirrhosa: Integrating herbal medicine production with biodiversity conservation

    Directory of Open Access Journals (Sweden)

    Xiwen Li

    2012-02-01

    Full Text Available Protected areas are generally regarded as a power tool to conserve biodiversity. Nonetheless, few protected areas could address three crucial problems simultaneously, namely funding, public participation and rural living. Here, we introduced a new protective approach, Natural Fostering, which integrated herbal medicine production with community conservation. The principles of Natural Fostering adopted species–species interaction at community level. Most effective chemical components of herbal medicine are derived from such interaction. Fritillaria cirrhosa was selected as an economic botany, one of herbal medicines, to carry out Natural Fostering. Community habitats, herbal medicine production, funding and income of local family were investigated to verify the feasibility of Natural Fostering for biodiversity. We found the density of plant populations and the annual average personal income of rural people increased. F. cirrhosa production could provide sufficient funds for sustainable conservation. Local people gradually changed their life style of wild collection and overgrazing, instead of herbal medicine production. The fostering area set up a good sustainable economic cycle. Natural Fostering can be presented as an effective and pragmatic way to conserve biological diversity and sustainable utilization of traditional medicinal resources.

  19. Natural product-like virtual libraries: recursive atom-based enumeration.

    Science.gov (United States)

    Yu, Melvin J

    2011-03-28

    A new molecular enumerator is described that allows chemically and architecturally diverse sets of natural product-like and drug-like structures to be generated from a core structure as simple as a single carbon atom or as complex as a polycyclic ring system. Integrated with a rudimentary machine-learning algorithm, the enumerator has the ability to assemble biased virtual libraries enriched in compounds predicted to meet target criteria. The ability to dynamically generate relatively small focused libraries in a recursive manner could reduce the computational time and infrastructure necessary to construct and manage extremely large static libraries. Depending on enumeration conditions, natural product-like structures can be produced with a wide range of heterocyclic and alicyclic ring assemblies. Because natural products represent a proven source of validated structures for identifying and designing new drug candidates, mimicking the structural and topological diversity found in nature with a dynamic set of virtual natural product-like compounds may facilitate the creation of new ideas for novel, biologically relevant lead structures in areas of uncharted chemical space.

  20. Forecasting natural gas supply in China: Production peak and import trends

    International Nuclear Information System (INIS)

    Lin Boqiang; Wang Ting

    2012-01-01

    China's natural gas consumption has increased rapidly in recent years making China a net gas importer. As a nonrenewable energy, the gas resource is exhaustible. Based on the forecast of this article, China's gas production peak is likely to approach in 2022. However, China is currently in the industrialization and urbanization stage, and its natural gas consumption will persistently increase. With China's gas production peak, China will have to face a massive expansion in gas imports. As the largest developing country, China's massive imports of gas will have an effect on the international gas market. In addition, as China's natural gas price is still controlled by the government and has remained at a low level, the massive imports of higher priced gas will exert great pressure on China's gas price reform. - Highlights: ► We figured out the natural gas production peak of China. ► We predict the import trends of natural gas of China. ► We study the international and national impacts of China's increasing import of gas. ► It is important for China to accelerate price reformation of natural gas.

  1. Marine Sponge Derived Natural Products between 2001 and 2010: Trends and Opportunities for Discovery of Bioactives

    Science.gov (United States)

    Mehbub, Mohammad Ferdous; Lei, Jie; Franco, Christopher; Zhang, Wei

    2014-01-01

    Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity of sponge-derived new natural products discovered between 2001 and 2010. The data has been analyzed with a view to gaining an outlook on the future trends and opportunities in the search for new compounds and their sources from marine sponges. PMID:25196730

  2. The paradox of natural products as pharmaceuticals. Experimental evidences of a mango stem bark extract.

    Science.gov (United States)

    Núñez-Sellés, Alberto J; Delgado-Hernández, René; Garrido-Garrido, Gabino; García-Rivera, Dagmar; Guevara-García, Mariela; Pardo-Andreu, Gilberto L

    2007-05-01

    Recent findings regarding basic, pre-clinical and clinical studies on a mango stem bark extract (MSBE) developed in Cuba (Vimang) on an industrial scale are summarized. Ethnomedical studies, extract reproducibility, biological effects and clinical evaluations in terms of patient quality of life are described as experimental evidences to support the statement that natural products, even being a mixture of compounds, could be as effective as "monoceuticals" for medical uses. Discussion about the use of "monoceuticals" versus "natureceuticals" in health care and medicine is based on effectiveness and availability, taking Vimang as an example of a natural product with supported scientific evidence to be used as antioxidant, analgesic, anti-inflammatory and immunomodulator.

  3. Epoxide-Opening Cascades in the Synthesis of Polycyclic Polyether Natural Products

    Science.gov (United States)

    2009-01-01

    The group of polycyclic polyether natural products is of special interest due to the fascinating structure and biological effects displayed by its members. The latter includes potentially therapeutic antibiotic, antifungal, and anticancer properties, as well as extreme lethality. The polycyclic structural features of this family can, in some cases, be traced to their biosynthetic origin, but in others that are less well understood, only to proposed biosynthetic pathways that feature dramatic, yet speculative, epoxide–opening cascades. In this review we summarize how such epoxide–opening cascade reactions have been used in the synthesis of polycyclic polyethers and related natural products. PMID:19572302

  4. Natural Products as Adjunctive Treatment for Pancreatic Cancer: Recent Trends and Advancements

    Directory of Open Access Journals (Sweden)

    Qingxi Yue

    2017-01-01

    Full Text Available Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.

  5. Recent Advances in the Discovery and Development of Marine Natural Products with Cardiovascular Pharmacological Effects.

    Science.gov (United States)

    Zhou, Jie-Bin; Luo, Rong; Zheng, Ying-Lin; Pang, Ji-Yan

    2018-01-01

    Numerous studies have indicated that marine natural products are one of the most important sources of the lead compounds in drug discovery for their unique structures, various bioactivities and less side effects. In this review, the marine natural products with cardiovascular pharmacological effects reported after 2000 will be presented. Their structural types, relevant biological activities, origin of isolation and information of strain species will be discussed in detail. Finally, by describing our studies as an example, we also discuss the chances and challenges for translating marine-derived compounds into preclinical or clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Expanding the range of 'druggable' targets with natural product-based libraries: an academic perspective.

    Science.gov (United States)

    Bauer, Renato A; Wurst, Jacqueline M; Tan, Derek S

    2010-06-01

    Existing drugs address a relatively narrow range of biological targets. As a result, libraries of drug-like molecules have proven ineffective against a variety of challenging targets, such as protein-protein interactions, nucleic acid complexes, and antibacterial modalities. In contrast, natural products are known to be effective at modulating such targets, and new libraries are being developed based on underrepresented scaffolds and regions of chemical space associated with natural products. This has led to several recent successes in identifying new chemical probes that address these challenging targets. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Structure of a putative fluorinated natural product from Streptomyces sp. TC1.

    Science.gov (United States)

    Aldemir, Hülya; Kohlhepp, Stefanie V; Gulder, Tanja; Gulder, Tobias A M

    2014-11-26

    Fluorine-containing natural products are extremely rare. The recent report on the isolation and biological activity of the bacterial secondary metabolite 3-(3,5-di-tert-butyl-4-fluorophenyl)propionic acid was thus highly remarkable. The compound contained the first aromatic fluorine substituent known to date in any natural product. The promise to discover an enzyme capable of aromatic fluorination in the producing strain Streptomyces sp. TC1 prompted our immediate interest. A close inspection of the originally reported analytical data of the fluoro metabolite revealed inconsistencies that triggered us to validate the reported structure. The results of these efforts are presented in this communication.

  8. Investigating the Structure-Activity Relationship of the Insecticidal Natural Product Rocaglamide.

    Science.gov (United States)

    Hall, Roger G; Bruce, Ian; Cooke, Nigel G; Diorazio, Louis J; Cederbaum, Fredrik; Dobler, Markus R; Irving, Ed

    2017-12-01

    The natural product Rocaglamide (1), isolated from the tree Aglaia elliptifolia, is a compelling but also challenging lead structure for crop protection. In laboratory assays, the natural product shows highly interesting insecticidal activity against chewing pests and beetles, but also phytotoxicity on some crop plants. Multi-step syntheses with control of stereochemistry were required to probe the structure-activity relationship (SAR), and seek simplified analogues. After a significant research effort, just two areas of the molecule were identified which allow modification whilst maintaining activity, as will be highlighted in this paper.

  9. The importance of asking "how and why?" in natural product structure elucidation.

    Science.gov (United States)

    Brown, Patrick D; Lawrence, Andrew L

    2017-10-18

    Covering: up to 2017This review highlights why careful consideration of the biosynthetic origin (the how) and the biological function (the why) of a natural product can be so useful during the determination of its structure. Recent examples of structural reassignments inspired by biosynthetic and functional insights will be presented. This review will demonstrate the importance of viewing the origin, structure and function of a natural product as intertwined threads of a single story, best viewed as a whole rather than as discrete topics.

  10. How does increased corn-ethanol production affect US natural gas prices?

    International Nuclear Information System (INIS)

    Whistance, Jarrett; Thompson, Wyatt

    2010-01-01

    In recent years, there has been a push to increase biofuel production in the United States. The biofuel of choice, so far, has been ethanol produced from corn. The effects of increased corn-ethanol production on the consumer prices of food and energy continue to be studied and debated. This study examines, in particular, the effects of increased corn-ethanol production on US natural gas prices. A structural model of the natural gas market is developed and estimated using two stage least squares. A baseline projection for the period 2007-2018 is determined, and two scenarios are simulated. In the first scenario, current biofuel policies including EISA mandates, tariffs, and tax credits are removed. In the second scenario, we hold ethanol production to the level required only for largely obligatory additive use. The results indicate that the increased level of corn-ethanol production occurring as a result of the current US biofuel policies may lead to natural gas prices that are as much as 0.25% higher, on average, than if no biofuel policies were in place. A similar comparison between the baseline and second scenario indicates natural gas prices could be as much as 0.5% higher, on average, for the same period.

  11. Quantifying methane emissions from natural gas production in north-eastern Pennsylvania

    Directory of Open Access Journals (Sweden)

    Z. R. Barkley

    2017-11-01

    Full Text Available Natural gas infrastructure releases methane (CH4, a potent greenhouse gas, into the atmosphere. The estimated emission rate associated with the production and transportation of natural gas is uncertain, hindering our understanding of its greenhouse footprint. This study presents a new application of inverse methodology for estimating regional emission rates from natural gas production and gathering facilities in north-eastern Pennsylvania. An inventory of CH4 emissions was compiled for major sources in Pennsylvania. This inventory served as input emission data for the Weather Research and Forecasting model with chemistry enabled (WRF-Chem, and atmospheric CH4 mole fraction fields were generated at 3 km resolution. Simulated atmospheric CH4 enhancements from WRF-Chem were compared to observations obtained from a 3-week flight campaign in May 2015. Modelled enhancements from sources not associated with upstream natural gas processes were assumed constant and known and therefore removed from the optimization procedure, creating a set of observed enhancements from natural gas only. Simulated emission rates from unconventional production were then adjusted to minimize the mismatch between aircraft observations and model-simulated mole fractions for 10 flights. To evaluate the method, an aircraft mass balance calculation was performed for four flights where conditions permitted its use. Using the model optimization approach, the weighted mean emission rate from unconventional natural gas production and gathering facilities in north-eastern Pennsylvania approach is found to be 0.36 % of total gas production, with a 2σ confidence interval between 0.27 and 0.45 % of production. Similarly, the mean emission estimates using the aircraft mass balance approach are calculated to be 0.40 % of regional natural gas production, with a 2σ confidence interval between 0.08 and 0.72 % of production. These emission rates as a percent of production are

  12. Quantifying methane emissions from natural gas production in north-eastern Pennsylvania

    Science.gov (United States)

    Barkley, Zachary R.; Lauvaux, Thomas; Davis, Kenneth J.; Deng, Aijun; Miles, Natasha L.; Richardson, Scott J.; Cao, Yanni; Sweeney, Colm; Karion, Anna; Smith, MacKenzie; Kort, Eric A.; Schwietzke, Stefan; Murphy, Thomas; Cervone, Guido; Martins, Douglas; Maasakkers, Joannes D.

    2017-11-01

    Natural gas infrastructure releases methane (CH4), a potent greenhouse gas, into the atmosphere. The estimated emission rate associated with the production and transportation of natural gas is uncertain, hindering our understanding of its greenhouse footprint. This study presents a new application of inverse methodology for estimating regional emission rates from natural gas production and gathering facilities in north-eastern Pennsylvania. An inventory of CH4 emissions was compiled for major sources in Pennsylvania. This inventory served as input emission data for the Weather Research and Forecasting model with chemistry enabled (WRF-Chem), and atmospheric CH4 mole fraction fields were generated at 3 km resolution. Simulated atmospheric CH4 enhancements from WRF-Chem were compared to observations obtained from a 3-week flight campaign in May 2015. Modelled enhancements from sources not associated with upstream natural gas processes were assumed constant and known and therefore removed from the optimization procedure, creating a set of observed enhancements from natural gas only. Simulated emission rates from unconventional production were then adjusted to minimize the mismatch between aircraft observations and model-simulated mole fractions for 10 flights. To evaluate the method, an aircraft mass balance calculation was performed for four flights where conditions permitted its use. Using the model optimization approach, the weighted mean emission rate from unconventional natural gas production and gathering facilities in north-eastern Pennsylvania approach is found to be 0.36 % of total gas production, with a 2σ confidence interval between 0.27 and 0.45 % of production. Similarly, the mean emission estimates using the aircraft mass balance approach are calculated to be 0.40 % of regional natural gas production, with a 2σ confidence interval between 0.08 and 0.72 % of production. These emission rates as a percent of production are lower than rates found in any

  13. Hacking an Algal Transcription Factor for Lipid Biosynthesis.

    Science.gov (United States)

    Chen, Xiulai; Hu, Guipeng; Liu, Liming

    2018-03-01

    Transcriptional engineering is a viable means for engineering microalgae to produce lipid, but it often results in a trade-off between production and growth. A recent study shows that engineering a single transcriptional regulator enables efficient carbon partitioning to lipid biosynthesis with high biomass productivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Technical review of coal gasifiers for production of synthetic natural gas

    International Nuclear Information System (INIS)

    Lee, Geun Woo; Shin, Yong Seung

    2012-01-01

    Because of the increasing cost of oil and natural gas, energy production technologies using coal, including synthetic natural gas (SNG) and integrated gasification combined cycle (IGCC), have attracted attention because of the relatively low cost of coal. During the early stage of a project, the developer or project owner has many options with regard to the selection of a gasifier. In particular, from the viewpoint of feasibility, the gasifier is a key factor in the economic evaluation. This study compares the technical aspects of gasifiers for a real SNG production project in an early stage. A fixed bed slagging gasifier, wet type entrained gasifier, and dry type entrained gasifier, all of which have specific advantages, can be used for the SNG production project. Base on a comparison of the process descriptions and performances of each gasifier, this study presents a selection guideline for a gasifier for an SNG production project that will be beneficial to project developers and EPC (Engineering, Procurement, Construction) contractors

  15. Economic growth to raise U.S. oil products, natural gas demand

    International Nuclear Information System (INIS)

    Beck, R.J.

    1994-01-01

    An accelerating economy will raise consumption of oil products and natural gas in the US this year. Contributing to demand growth will be the slump that began late last year in prices for crude oil and petroleum products. Some price recovery is likely in 1994, but there's little reason to expect a major increase. With oil production falling and demand rising, imports will have to climb again this year. OGJ projects a 2.6% increase this year following a 6.6% increase last year. Imports are expected to fill a record high 49.3% of US oil demand this year. The paper discusses energy and the economy, overall energy use, energy by source, the electrification trend, energy supplies, imports, refining operations, the growth of margins, and the energy demand of motor gasoline, jet fuel, distillate fuels, residual fuel oils, other petroleum products, and natural gas

  16. 46_ _267 - 278__Aminu- Biosynthesis

    African Journals Online (AJOL)

    User

    ISSN 2006 – 6996. BIOSYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL STUDY OF .... the excitation of surface Plasmon vibration with. AgNPs. ... Thin films of the sample were prepared on a carbon ... The resulting film on the SEM.

  17. Cellulose biosynthesis in higher plants

    Directory of Open Access Journals (Sweden)

    Krystyna Kudlicka

    2014-01-01

    Full Text Available Knowledge of the control and regulation of cellulose synthesis is fundamental to an understanding of plant development since cellulose is the primary structural component of plant cell walls. In vivo, the polymerization step requires a coordinated transport of substrates across membranes and relies on delicate orientations of the membrane-associated synthase complexes. Little is known about the properties of the enzyme complexes, and many questions about the biosynthesis of cell wall components at the cell surface still remain unanswered. Attempts to purify cellulose synthase from higher plants have not been successful because of the liability of enzymes upon isolation and lack of reliable in vitro assays. Membrane preparations from higher plant cells incorporate UDP-glucose into a glucan polymer, but this invariably turns out to be predominantly β -1,3-linked rather than β -1,4-linked glucans. Various hypotheses have been advanced to explain this phenomenon. One idea is that callose and cellulose-synthase systems are the same, but cell disruption activates callose synthesis preferentially. A second concept suggests that a regulatory protein as a part of the cellulose-synthase complex is rapidly degraded upon cell disruption. With new methods of enzyme isolation and analysis of the in vitro product, recent advances have been made in the isolation of an active synthase from the plasma membrane whereby cellulose synthase was separated from callose synthase.

  18. Control of Cowpea Weevil, Callosobruchus Maculatus (F.) (Coleoptera: Bruchidae), Using Natural Plant Products

    OpenAIRE

    Tiroesele, Bamphitlhi; Thomas, Kesegofetse; Seketeme, Seipati

    2014-01-01

    A laboratory study was conducted to investigate the effects of natural products on the reproduction and damage of Callosobruchus maculatus, the cowpea weevil, on cowpea seeds at Botswana College of Agriculture in Gaborone, Botswana. The cowpea variety Blackeye was used in the study. Fifty grams of each plant product (garlic, peppermint and chilies) was added to 500 g of the cowpea seeds. Findings of this experiment revealed that chilies and garlic had negative effects on cowpea weevils for al...

  19. Tolerance of natural baby skin-care products on healthy, full-term infants and toddlers.

    Science.gov (United States)

    Coret, Catherine D; Suero, Michael B; Tierney, Neena K

    2014-01-01

    To evaluate the tolerance of baby skin-care products with at least 95% naturally derived ingredients on infants and toddlers. Healthy, full-term infants and toddlers aged 1-36 months were enrolled. In study 1, a lightly fragranced natural baby hair and body wash (n=30), a lightly fragranced natural baby shampoo (n=30), or a lightly fragranced natural baby lotion (n=32) were assessed over 2 weeks. In study 2, a lightly fragranced natural baby hair and body wash and a lightly fragranced natural baby lotion (n=33) were assessed as a regimen over 4 weeks. The wash and shampoo were used three or more times per week, but not more than once daily. Lotions were applied in the morning or after a bath. Clinicians assessed the arms, legs, torso, or scalp for erythema, dryness, peeling/flakiness (study 1 only), tactile roughness, edema (study 1 only), rash/irritation (study 2 only), and overall skin condition (study 2 only) at baseline, week 1, and weeks 2 or 4. Parents completed skin assessment questionnaires. In study 2, stratum corneum hydration was measured. Subjects were monitored for adverse events. No significant changes in clinical grading scores were observed, indicating that all products were well tolerated. By the end of each study, >90% of parents/caregivers believed each product was mild and gentle. In study 2, improvement in stratum corneum hydration was observed (+37% at week 1 and +48% at week 4, Pproduct-related adverse events. The natural baby skin-care products were well tolerated by infants and toddlers when used alone or as part of a skin-care regimen.

  20. Production Of Hollow Toy Product From Radiation Pre vulcanized Natural Rubber Latex (RVNRL) By Using Casting And Moulding Technique

    International Nuclear Information System (INIS)

    Mohd Noorwadi Mat Lazim; Sofian Ibrahim; Muhammad Saiful Omar

    2013-01-01

    Hollow toy products are very synonym to the child from the age of months since it able to stimulating each of their sense such as sight, hearing, taste, touch and smell. Most of hollow toy products are made from natural rubber latex by using moulding and casting technique. The moulding and casting technique is a manufacturing process by pored liquid latex into a mould, which contain cavity of the desired shape. The mould made from plaster of Paris able to absorbs water from latex meanwhile the presence of calcium ions from plaster of Paris will tend to diffuse into latex thus promote formation of deposit on surface of cavity mould. To improve the quality and safety of hollow toy product made from latex, Radiation Pre vulcanized Natural Rubber Latex (RVNRL) has been identified to be used because it can fulfill the standard requirement for latex and also due to its special abilities such as lower modulus (soft latex products), nitrosamines free, low in nitrosatables, free from chemical accelerators induced allergies and better biodegradability. This paper identify the problem appears from the process of making hollow toy products from RVNRL by using moulding and casting technique. (author)