Novel Tandem Biotransformation Process for the Biosynthesis of a Novel Compound, 4-(2,3,5,6-Tetramethylpyrazine-1)-4′-Demethylepipodophyllotoxin▿

Science.gov (United States)

Tang, Ya-Jie; Zhao, Wei; Li, Hong-Mei

2011-01-01

According to the structure of podophyllotoxin and its structure-function relationship, a novel tandem biotransformation process was developed for the directional modification of the podophyllotoxin structure to directionally synthesize a novel compound, 4-(2,3,5,6-tetramethylpyrazine-1)-4′-demethylepipodophyllotoxin (4-TMP-DMEP). In this novel tandem biotransformation process, the starting substrate of podophyllotoxin was biotransformed into 4′-demethylepipodophyllotoxin (product 1) with the demethylation of the methoxyl group at the 4′ position by Gibberella fujikuroi SH-f13, which was screened out from Shennongjia prime forest humus soil (Hubei, China). 4′-Demethylepipodophyllotoxin (product 1) was then biotransformed into 4′-demethylpodophyllotoxone (product 2) with the oxidation of the hydroxyl group at the 4 position by Alternaria alternata S-f6, which was screened out from the gathered Dysosma versipellis plants in the Wuhan Botanical Garden, Chinese Academy of Sciences. Finally, 4′-demethylpodophyllotoxone (product 2) and ligustrazine were linked with a transamination reaction to synthesize the target product 4-TMP-DMEP (product 3) by Alternaria alternata S-f6. Compared with podophyllotoxin (i.e., a 50% effective concentration [EC50] of 529 μM), the EC50 of 4-TMP-DMEP against the tumor cell line BGC-823 (i.e., 0.11 μM) was significantly reduced by 5,199 times. Simultaneously, the EC50 of 4-TMP-DMEP against the normal human proximal tubular epithelial cell line HK-2 (i.e., 0.40 μM) was 66 times higher than that of podophyllotoxin (i.e., 0.006 μM). Furthermore, compared with podophyllotoxin (i.e., log P = 0.34), the water solubility of 4-TMP-DMEP (i.e., log P = 0.66) was significantly enhanced by 94%. For the first time, the novel compound 4-TMP-DMEP with superior antitumor activity was directionally synthesized from podophyllotoxin by the novel tandem biotransformation process developed in this work. PMID:21398491

Biotransformation of limonene by an endophytic fungus using synthetic and orange residue-based media.

Science.gov (United States)

Bier, Mário Cesar Jucoski; Medeiros, Adriane Bianchi Pedroni; Soccol, Carlos Ricardo

2017-02-01

Aroma and fragrances have high commercial value for use in food, cosmetics and perfumes. The biotransformation of terpenes by microorganisms represents an attractive alternative method for production of flavourings. Endophytic fungi offer a great potential for the production of several groups of compounds; however, few studies have evaluated the biotransformation of limonene. Following preliminary studies on the biotransformation of limonene, submerged fermentation was carried out using an endophytic fungus isolated from Pinus taeda and identified as Phomopsis sp. The presence of several biotransformation products was detected and identified by mass spectrometry (GC-MS). The studied strain showed a divergent metabolic behaviour, as compounds of interest such as α-terpineol, carvone, and limoneno-1,2-diol were produced under different conditions. In addition to the minor metabolites terpinen-4-ol, menthol and carveol, this strain also produced major metabolites, including 0.536 g L -1 carvone and 2.08 g L -1 limonene-1,2-diol in synthetic medium and 2.10 g L -1 limonene-1,2-diol in a natural orange extract medium with single fed-batch, while the cyclic fed-batch resulted in concentrations less than 1 g L -1 . Therefore, our study produced a wide variety of limonene derivatives at a high concentration using a natural medium and a newly isolated endophytic fungal strain. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Biotransformation of sclareolide by filamentous fungi: cytotoxic evaluations of the derivatives

Energy Technology Data Exchange (ETDEWEB)

Cano, Arturo [Universidad Nacional Autonoma de Mexico, D.F. (Mexico). Facultad de Estudios Superiores Zaragoza; Ramirez-Apan, Maria Teresa; Delgado, Guillermo, E-mail: delgado@unam.m [Universidad Nacional Autonoma de Mexico, D.F. (Mexico)

2011-07-01

Sclareolide (1) was incubated with eight different species of filamentous fungi conventionally used for bio-oxidations. Compound 1 was metabolized with Aspergillus niger in medium A to yield 3-ketosclareolide (2) and 3b-hydroxysclareolide (4), while in medium B (containing major number of nutrients with respect to medium A), compounds 2, 4, 3{alpha},6{beta}-dihydroxysclareolide (16), 1-ketosclareolide (17), 3-keto-15-hydroxysclareolide (18) and 3{beta},15-dihydroxysclareolide (19) were obtained. The biotransformation products 16-19 were found to be new substances. Fermentation of 1 with Cunninghamella blackesleeana using medium A afforded 2 and 4, while using medium B yielded 2, 4, 16 and 17. Compounds 2, 4 and 17 were also obtained with Curvularia lunata. Biotransformation of 1 with Beauveria bassiana yielded 4 in satisfactory yield, with Rhizopus oligosporus and Mucor miehei afforded 2 and 4, while with R. nigricans and Fusarium moliniforme yielded 2, 4 and 16. Cytotoxic evaluation of 1 and the obtained products against selected human cancer cell lines (U251, PC-3, K562, HCT-15, MCF-7 and SKUL-1) indicated that 16 (3{alpha},6{beta}-dihydroxysclareolide) displayed moderate cytotoxic (IC{sub 50} < 100 {mu}M) against U251, PC-3, HCT-15 and MCF-7. (author)

Biotransformation of sclareolide by filamentous fungi: cytotoxic evaluations of the derivatives

International Nuclear Information System (INIS)

Cano, Arturo

2011-01-01

Sclareolide (1) was incubated with eight different species of filamentous fungi conventionally used for bio-oxidations. Compound 1 was metabolized with Aspergillus niger in medium A to yield 3-ketosclareolide (2) and 3b-hydroxysclareolide (4), while in medium B (containing major number of nutrients with respect to medium A), compounds 2, 4, 3α,6β-dihydroxysclareolide (16), 1-ketosclareolide (17), 3-keto-15-hydroxysclareolide (18) and 3β,15-dihydroxysclareolide (19) were obtained. The biotransformation products 16-19 were found to be new substances. Fermentation of 1 with Cunninghamella blackesleeana using medium A afforded 2 and 4, while using medium B yielded 2, 4, 16 and 17. Compounds 2, 4 and 17 were also obtained with Curvularia lunata. Biotransformation of 1 with Beauveria bassiana yielded 4 in satisfactory yield, with Rhizopus oligosporus and Mucor miehei afforded 2 and 4, while with R. nigricans and Fusarium moliniforme yielded 2, 4 and 16. Cytotoxic evaluation of 1 and the obtained products against selected human cancer cell lines (U251, PC-3, K562, HCT-15, MCF-7 and SKUL-1) indicated that 16 (3α,6β-dihydroxysclareolide) displayed moderate cytotoxic (IC 50 < 100 μM) against U251, PC-3, HCT-15 and MCF-7. (author)

Glycyrrhiza glabra (Linn.) and Lavandula officinalis (L.) cell suspension cultures-based biotransformation of β-artemether.

Science.gov (United States)

Patel, Suman; Gaur, Rashmi; Upadhyaya, Mohita; Mathur, Archana; Mathur, Ajay K; Bhakuni, Rajendra S

2011-07-01

The biotransformation of β-artemether (1) by cell suspension cultures of Glycyrrhiza glabra and Lavandula officinalis is reported here for the first time. The major biotransformed product appeared as a grayish-blue color spot on thin-layer chromatography (TLC) with transparent crystal-like texture. Based on its infrared (IR) and (1)H nuclear magnetic resonance (NMR) spectra, the product was characterized as a tetrahydrofuran (THF)-acetate derivative (2). The highest conversion efficiencies of 57 and 60% were obtained when 8-9-day-old cell suspensions of G. glabra and L. officinalis were respectively fed with 4-7 mg of compound 1 in 40 ml of medium per culture and the cells were harvested after 2-5 days of incubation. The addition of compound 1 at the beginning of the culture cycle caused severe growth depression in a dose-dependent manner, resulting in poor bioconversion efficiency of ~25% at 2-5 mg/culture dose only.

Perspective on Biotransformation and De Novo Biosynthesis of Licorice Constituents.

Science.gov (United States)

Zhao, Yujia; Lv, Bo; Feng, Xudong; Li, Chun

2017-12-27

Licorice, an important herbal medicine, is derived from the dried roots and rhizomes of Glycyrrhiza genus plants. It has been widely used in food, pharmaceutical, tobacco, and cosmetics industries with high economic value. However, overexploitation of licorice resources has severely destroyed the local ecology. Therefore, producing bioactive compounds of licorice through the biotransformation and bioengineering methods is a hot spot in recent years. In this perspective, we comprehensively summarize the biotransformation of licorice constituents into high-value-added derivatives by biocatalysts. Furthermore, successful cases and the strategies for de novo biosynthesizing compounds of licorice in microbes have been summarized. This paper will provide new insights for the further research of licorice.

Biotransformation model of neutral and weakly polar organic compounds in fish incorporating internal partitioning.

Science.gov (United States)

Kuo, Dave T F; Di Toro, Dominic M

2013-08-01

A model for whole-body in vivo biotransformation of neutral and weakly polar organic chemicals in fish is presented. It considers internal chemical partitioning and uses Abraham solvation parameters as reactivity descriptors. It assumes that only chemicals freely dissolved in the body fluid may bind with enzymes and subsequently undergo biotransformation reactions. Consequently, the whole-body biotransformation rate of a chemical is retarded by the extent of its distribution in different biological compartments. Using a randomly generated training set (n = 64), the biotransformation model is found to be: log (HLφfish ) = 2.2 (±0.3)B - 2.1 (±0.2)V - 0.6 (±0.3) (root mean square error of prediction [RMSE] = 0.71), where HL is the whole-body biotransformation half-life in days, φfish is the freely dissolved fraction in body fluid, and B and V are the chemical's H-bond acceptance capacity and molecular volume. Abraham-type linear free energy equations were also developed for lipid-water (Klipidw ) and protein-water (Kprotw ) partition coefficients needed for the computation of φfish from independent determinations. These were found to be 1) log Klipidw  = 0.77E - 1.10S - 0.47A - 3.52B + 3.37V + 0.84 (in Lwat /kglipid ; n = 248, RMSE = 0.57) and 2) log Kprotw  = 0.74E - 0.37S - 0.13A - 1.37B + 1.06V - 0.88 (in Lwat /kgprot ; n = 69, RMSE = 0.38), where E, S, and A quantify dispersive/polarization, dipolar, and H-bond-donating interactions, respectively. The biotransformation model performs well in the validation of HL (n = 424, RMSE = 0.71). The predicted rate constants do not exceed the transport limit due to circulatory flow. Furthermore, the model adequately captures variation in biotransformation rate between chemicals with varying log octanol-water partitioning coefficient, B, and V and exhibits high degree of independence from the choice of training chemicals. The

Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil

International Nuclear Information System (INIS)

Liu, Chen; Liu, Jinxia

2016-01-01

Microbial transformation of polyfluoroalkyl phosphate esters (PAPs) into perfluorocarboxylic acids (PFCAs) has recently been confirmed to occur in activated sludge and soil. However, there lacks quantitative information about the half-lives of the PAPs and their significance as the precursors to PFCAs. In the present study, the biotransformation of 6:2 and 8:2 diPAP in aerobic soil was investigated in semi-dynamics reactors using improved sample preparation methods. To develop an efficient extraction method for PAPs, six different extraction solvents were compared, and the phenomenon of solvent-enhanced hydrolysis was investigated. It was found that adding acetic acid could enhance the recoveries of the diPAPs and inhibit undesirable hydrolysis during solvent extraction of soil. However 6:2 and 8:2 monoPAPs, which are the first breakdown products from diPAPs, were found to be unstable in the six solvents tested and quickly hydrolyzed to form fluorotelomer alcohols. Therefore reliable measurement of the monoPAPs from a live soil was not achievable. The apparent DT_5_0 values of 6:2 diPAP and 8:2 diPAP biotransformation were estimated to be 12 and > 1000 days, respectively, using a double first-order in parallel model. At the end of incubation of day 112, the major degradation products of 6:2 diPAP were 5:3 fluorotelomer carboxylic acid (5:3 acid, 9.3% by mole), perfluoropentanoic acid (PFPeA, 6.4%) and perfluorohexanoic acid (PFHxA, 6.0%). The primary product of 8:2 diPAP was perfluorooctanoic acid (PFOA, 2.1%). The approximately linear relationship between the half-lives of eleven polyfluoroalkyl and perfluoroalkyl substances (PFASs, including 6:2 and 8:2 diPAPs) that biotransform in aerobic soils and their molecular weights suggested that the molecular weight is a good indicator of the general stability of low-molecular-weight PFAS-based compounds in aerobic soils. - Highlights: • Biotransformation of 6:2 and 8:2 diPAPs in an aerobic soil was investigated. �

Applications and Mechanisms of Ionic Liquids in Whole-Cell Biotransformation

Science.gov (United States)

Fan, Lin-Lin; Li, Hong-Ji; Chen, Qi-He

2014-01-01

Ionic liquids (ILs), entirely composed of cations and anions, are liquid solvents at room temperature. They are interesting due to their low vapor pressure, high polarity and thermostability, and also for the possibility to fine-tune their physicochemical properties through modification of the chemical structures of their cations or anions. In recent years, ILs have been widely used in biotechnological fields involving whole-cell biotransformations of biodiesel or biomass, and organic compound synthesis with cells. Research studies in these fields have increased from the past decades and compared to the typical solvents, ILs are the most promising alternative solvents for cell biotransformations. However, there are increasing limitations and new challenges in whole-cell biotransformations with ILs. There is little understanding of the mechanisms of ILs’ interactions with cells, and much remains to be clarified. Further investigations are required to overcome the drawbacks of their applications and to broaden their application spectrum. This work mainly reviews the applications of ILs in whole-cell biotransformations, and the possible mechanisms of ILs in microbial cell biotransformation are proposed and discussed. PMID:25007820

Applications and mechanisms of ionic liquids in whole-cell biotransformation.

Science.gov (United States)

Fan, Lin-Lin; Li, Hong-Ji; Chen, Qi-He

2014-07-09

Ionic liquids (ILs), entirely composed of cations and anions, are liquid solvents at room temperature. They are interesting due to their low vapor pressure, high polarity and thermostability, and also for the possibility to fine-tune their physicochemical properties through modification of the chemical structures of their cations or anions. In recent years, ILs have been widely used in biotechnological fields involving whole-cell biotransformations of biodiesel or biomass, and organic compound synthesis with cells. Research studies in these fields have increased from the past decades and compared to the typical solvents, ILs are the most promising alternative solvents for cell biotransformations. However, there are increasing limitations and new challenges in whole-cell biotransformations with ILs. There is little understanding of the mechanisms of ILs' interactions with cells, and much remains to be clarified. Further investigations are required to overcome the drawbacks of their applications and to broaden their application spectrum. This work mainly reviews the applications of ILs in whole-cell biotransformations, and the possible mechanisms of ILs in microbial cell biotransformation are proposed and discussed.

Mercury Analysis of Acid- and Alkaline-Reduced Biological Samples: Identification of meta-Cinnabar as the Major Biotransformed Compound in Algae†

OpenAIRE

Kelly, David; Budd, Kenneth; Lefebvre, Daniel D.

2006-01-01

The biotransformation of HgII in pH-controlled and aerated algal cultures was investigated. Previous researchers have observed losses in Hg detection in vitro with the addition of cysteine under acid reduction conditions in the presence of SnCl2. They proposed that this was the effect of Hg-thiol complexing. The present study found that cysteine-Hg, protein and nonprotein thiol chelates, and nucleoside chelates of Hg were all fully detectable under acid reduction conditions without previous d...

The role of biotransformation in dietary (anti)carcinogenesis

NARCIS (Netherlands)

Iersel, M.L.P.S. van; Verhagen, H.; Bladeren, P.J. van

1999-01-01

The fact that dietary compounds influence the susceptibility of human beings to cancer, is widely accepted. One of the possible mechanisms that is responsible for these (anti)carcinogenic effects is that dietary constituents may modulate biotransformation enzymes, thereby affecting the

Biotransformation of Trichoderma spp. and their tolerance to aromatic amines, a major class of pollutants.

Science.gov (United States)

Cocaign, Angélique; Bui, Linh-Chi; Silar, Philippe; Chan Ho Tong, Laetitia; Busi, Florent; Lamouri, Aazdine; Mougin, Christian; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Dairou, Julien

2013-08-01

Trichoderma spp. are cosmopolitan soil fungi that are highly resistant to many toxic compounds. Here, we show that Trichoderma virens and T. reesei are tolerant to aromatic amines (AA), a major class of pollutants including the highly toxic pesticide residue 3,4-dichloroaniline (3,4-DCA). In a previous study, we provided proof-of-concept remediation experiments in which another soil fungus, Podospora anserina, detoxifies 3,4-DCA through its arylamine N-acetyltransferase (NAT), a xenobiotic-metabolizing enzyme that enables acetyl coenzyme A-dependent detoxification of AA. To assess whether the N-acetylation pathway enables AA tolerance in Trichoderma spp., we cloned and characterized NATs from T. virens and T. reesei. We characterized recombinant enzymes by determining their catalytic efficiencies toward several toxic AA. Through a complementary approach, we also demonstrate that both Trichoderma species efficiently metabolize 3,4-DCA. Finally, we provide evidence that NAT-independent transformation is solely (in T. virens) or mainly (in T. reesei) responsible for the observed removal of 3,4-DCA. We conclude that T. virens and, to a lesser extent, T. reesei likely utilize another, unidentified, metabolic pathway for the detoxification of AA aside from acetylation. This is the first molecular and functional characterization of AA biotransformation in Trichoderma spp. Given the potential of Trichoderma for cleanup of contaminated soils, these results reveal new possibilities in the fungal remediation of AA-contaminated soil.

Biotransformation of chalcones by the endophytic fungus Aspergillus flavus isolated from Paspalum maritimum trin

Energy Technology Data Exchange (ETDEWEB)

Correa, Marivaldo J.C.; Nunes, Fatima M.; Bitencourt, Heriberto R.; Borges, Fabio C.; Guilhon, Giselle M.S.P.; Arruda, Mara S.P.; Marinho, Andrey M. R.; Santos, Alberdan S.; Alves, Claudio N.; Santos, Lourivaldo S., E-mail: lss@ufpa.b [Universidade Federal do Para (IQ/FEQ/UFPA), Belem, PA (Brazil). Inst. de Tecnologia. Faculdade de Engenharia Quimica; Brasil, Davi S.B. [Universidade Federal do Para (PPGQ/IQ/UFPA), Belem, PA (Brazil). Inst. de Quimica. Programa de Pos-Graduacao em Quimica

2011-07-01

The fungus Aspergillus flavus isolated as endophytic of the plant Paspalum maritimum Trin. was evaluated for its potential application in biotransformation reactions. The compounds chalcone (1), 3,4,5-trimethoxychalcone (2) and 2,3,4,4'-tetramethoxy chalcone (3) were biotransformed, respectively, in dihydrochalcone (4), 3,4,5-trimethoxydihydrochalcone (5) and 2,3,4,4'-tetramethoxydihydrochalcone (6). The structures were elucidated by spectroscopic methods including 1D and 2D NMR techniques, and MS analysis. The dihydrochalcones 5 and 6 are new compounds. (author)

Biotransformation of chalcones by the endophytic fungus Aspergillus flavus isolated from Paspalum maritimum trin

International Nuclear Information System (INIS)

Correa, Marivaldo J.C.; Nunes, Fatima M.; Bitencourt, Heriberto R.; Borges, Fabio C.; Guilhon, Giselle M.S.P.; Arruda, Mara S.P.; Marinho, Andrey M. R.; Santos, Alberdan S.; Alves, Claudio N.; Santos, Lourivaldo S.; Brasil, Davi S.B.

2011-01-01

The fungus Aspergillus flavus isolated as endophytic of the plant Paspalum maritimum Trin. was evaluated for its potential application in biotransformation reactions. The compounds chalcone (1), 3,4,5-trimethoxychalcone (2) and 2,3,4,4'-tetramethoxy chalcone (3) were biotransformed, respectively, in dihydrochalcone (4), 3,4,5-trimethoxydihydrochalcone (5) and 2,3,4,4'-tetramethoxydihydrochalcone (6). The structures were elucidated by spectroscopic methods including 1D and 2D NMR techniques, and MS analysis. The dihydrochalcones 5 and 6 are new compounds. (author)

Biotransformation of tetracycline by a novel bacterial strain Stenotrophomonas maltophilia DT1.

Science.gov (United States)

Leng, Yifei; Bao, Jianguo; Chang, Gaofeng; Zheng, Han; Li, Xingxing; Du, Jiangkun; Snow, Daniel; Li, Xu

2016-11-15

Although several abiotic processes have been reported that can transform antibiotics, little is known about whether and how microbiological processes may degrade antibiotics in the environment. This work isolated one tetracycline degrading bacterial strain, Stenotrophomonas maltophilia strain DT1, and characterized the biotransformation of tetracycline by DT1 under various environmental conditions. The biotransformation rate was the highest when the initial pH was 9 and the reaction temperature was at 30°C, and can be described using the Michaelis-Menten model under different initial tetracycline concentrations. When additional substrate was present, the substrate that caused increased biomass resulted in a decreased biotransformation rate of tetracycline. According to disk diffusion tests, the biotransformation products of tetracycline had lower antibiotic potency than the parent compound. Six possible biotransformation products were identified, and a potential biotransformation pathway was proposed that included sequential removal of N-methyl, carbonyl, and amine function groups. Results from this study can lead to better estimation of the fate and transport of antibiotics in the environment and has the potential to be utilized in designing engineering processes to remove tetracycline from water and soil. Copyright © 2016 Elsevier B.V. All rights reserved.

White rot fungi and advanced combined biotechnology with nanomaterials: promising tools for endocrine-disrupting compounds biotransformation.

Science.gov (United States)

Huang, Danlian; Guo, Xueying; Peng, Zhiwei; Zeng, Guangming; Xu, Piao; Gong, Xiaomin; Deng, Rui; Xue, Wenjing; Wang, Rongzhong; Yi, Huan; Liu, Caihong

2017-10-29

Endocrine-disrupting compounds (EDCs) can interfere with endocrine systems and bio-accumulate through the food chain and even decrease biodiversity in contaminated areas. This review discusses a critical overview of recent research progress in the biotransformation of EDCs (including polychlorinated biphenyl and nonylphenol, and suspected EDCs such as heavy metals and sulfonamide antibiotics) by white rot fungi (WRF) based on techniques with an emphasis on summarizing and analyzing fungal molecular, metabolic and genetic mechanisms. Not only intracellular metabolism which seems to perform essential roles in the ability of WRF to transform EDCs, but also advanced applications are deeply discussed. This review mainly reveals the removal pathway of heavy metal and antibiotic pollutants because the single pollution almost did not exist in a real environment while the combined pollution has become more serious and close to people's life. The trends in WRF technology and its related advanced applications which use the combined technology, including biocatalysis of WRF and adsorption of nanomaterials, to degrade EDCs have also been introduced. Furthermore, challenges and future research needs EDCs biotransformation by WRF are also discussed. This research, referring to metabolic mechanisms and the combined technology of WRF with nanomaterials, undoubtedly contributes to the applications of biotechnology. This review will be of great benefit to an understanding of the trends in biotechnology for the removal of EDCs.

Trypsin inhibitory activity of artemisinin and its biotransformed product

International Nuclear Information System (INIS)

Shahwar, D.; Raza, M.A.

2013-01-01

Summary: Artemisinin (1 ), a sesquiterpene lactone is an important constituent of anti-malarial drugs. In the present study, it was extracted from aerial parts of Artemisia roxburghiana Besser. Biotransformation of artemisinin ( 1 ) was carried out in the culture of Aspergillus niger GC-4 which yielded 5-hydroxy artemisinin (2 ) The structures of 1-2 were confirmed through spectral studies. Both compounds were screened against trypsin using colorimetric method. The biotransformed product 2 showed significant protease inhibitory activity with 53.5 +- 1.6% inhibition and IC/sub 50/ = 0.29 +- 0.02 mM as compared to artemisinin (20.4 +- 0.3% inhibition). (author)

Comparison of the disposition of several nitrogen-containing compounds in the sea urchin and other marine invertebrates

Energy Technology Data Exchange (ETDEWEB)

Landrum, P.F.; Crosby, D.G.

1981-01-01

1. The disposition of an aromatic amine and three aromatic nitro compounds was investigated in the sea urchin, Strongylocentrotus purpuratus. 2. The sea urchin rapidly eliminated injected compounds. The elimination rate constants decreased in the order p-toluidine greater than p-nitroanisole . p-nitrophenol greater than p-nitrotoluene. The fraction of total injected compound eliminated in 8 h was lowest for p-nitrophenol less than p-toluidine less than p-nitrotoluene less than p-nitroanisole. 3. Biotransformation for the sea urchin was primarily reduction of the nitro group followed by acetylation of the amine. 4. Other animals, starfish (Pisaster ochraceus), sea cucumber (Cucumaria miniata), gum boot chiton (Cryptochiton stelleri) and mussels (Mytilus californianus), injected with p-nitroanisole exhibited a trend toward oxidative biotransformation. 5. Elimination of parent compound was the major pathway for reducing body burden of xenobiotics for the invertebrates studied. 6. p-Toluidine oxidizes during analysis and was thus not suitable for studying biotransformation.

Factors impacting biotransformation kinetics of trace organic compounds in lab-scale activated sludge systems performing nitrification and denitrification

Energy Technology Data Exchange (ETDEWEB)

Su, Lijuan; Aga, Diana [Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Chandran, Kartik [Department of Earth and Environmental Engineering, Columbia University, New York, NY 10027 (United States); Khunjar, Wendell O., E-mail: wkhunjar@hazenandsawyer.com [Hazen and Sawyer P.C., Fairfax, VA 22030 (United States)

2015-01-23

Highlights: • We examined TOrC biotransformation kinetics in nitrifying and denitrifying reators. • TOrC biotransformation was linked to heterotrophic and autotrophic activity. • TOrC biotransformation rates were not sensitive to the initial TOrC concentration. • Readily biodegradable organic matter suppressed TOrC biotransformation rates. - Abstract: To predict TOrC fate in biological activated sludge systems, there is a need to accurately determine TOrC biodegradation kinetics in mixed microbial cultures. Short-term batch tests with salicylic acid, 17α-ethinylestradiol, nonylphenol, trimethoprim and carbamazepine were conducted with lab-scale activated sludge cultures in which the initial TOrC concentration (1 mg/L and 0.0005 mg/L) and readily biodegradable substrate concentrations were varied. The results indicate that pseudo-first order kinetic estimates of TOrC are not sensitive (p > 0.05) to the initial TOrC concentration as long as the initial TOrC concentration (S{sub 0}) to biomass (X{sub 0}) ratio (on COD basis) is below 2 × 10{sup −3}. The presence of readily biodegradable organic matter suppresses TOrC biotransformation rates under nitrifying and denitrifying conditions, and this impact can be adequately described using a reversible non-competitive inhibition equation. These results demonstrate the importance of closely mimicking parent reactor conditions in batch testing because biotransformation parameters are impacted by in-situ carbon loading and redox conditions.

Factors impacting biotransformation kinetics of trace organic compounds in lab-scale activated sludge systems performing nitrification and denitrification

International Nuclear Information System (INIS)

Su, Lijuan; Aga, Diana; Chandran, Kartik; Khunjar, Wendell O.

2015-01-01

Highlights: • We examined TOrC biotransformation kinetics in nitrifying and denitrifying reators. • TOrC biotransformation was linked to heterotrophic and autotrophic activity. • TOrC biotransformation rates were not sensitive to the initial TOrC concentration. • Readily biodegradable organic matter suppressed TOrC biotransformation rates. - Abstract: To predict TOrC fate in biological activated sludge systems, there is a need to accurately determine TOrC biodegradation kinetics in mixed microbial cultures. Short-term batch tests with salicylic acid, 17α-ethinylestradiol, nonylphenol, trimethoprim and carbamazepine were conducted with lab-scale activated sludge cultures in which the initial TOrC concentration (1 mg/L and 0.0005 mg/L) and readily biodegradable substrate concentrations were varied. The results indicate that pseudo-first order kinetic estimates of TOrC are not sensitive (p > 0.05) to the initial TOrC concentration as long as the initial TOrC concentration (S 0 ) to biomass (X 0 ) ratio (on COD basis) is below 2 × 10 −3 . The presence of readily biodegradable organic matter suppresses TOrC biotransformation rates under nitrifying and denitrifying conditions, and this impact can be adequately described using a reversible non-competitive inhibition equation. These results demonstrate the importance of closely mimicking parent reactor conditions in batch testing because biotransformation parameters are impacted by in-situ carbon loading and redox conditions

Modeling of Pharmaceutical Biotransformation by Enriched Nitrifying Culture under Different Metabolic Conditions

DEFF Research Database (Denmark)

Xu, Yifeng; Chen, Xueming; Yuan, Zhiguo

2018-01-01

Pharmaceutical removal could be significantly enhanced through cometabolism during nitrification processes. To date, pharmaceutical biotransformation models have not considered the formation of transformation products associated with the metabolic type of microorganisms. Here we report a comprehe......Pharmaceutical removal could be significantly enhanced through cometabolism during nitrification processes. To date, pharmaceutical biotransformation models have not considered the formation of transformation products associated with the metabolic type of microorganisms. Here we report...... a comprehensive model to describe and evaluate the biodegradation of pharmaceuticals and the formation of their biotransformation products by enriched nitrifying cultures. The biotransformation of parent compounds was linked to the microbial processes via cometabolism induced by ammonium-oxidizing bacteria (AOB......) growth, metabolism by AOB, cometabolism by heterotrophs (HET) growth, and metabolism by HET in the model framework. The model was calibrated and validated using experimental data from pharmaceutical biodegradation experiments at realistic levels, taking two pharmaceuticals as examples, i.e., atenolol...

Dynamic Passive Dosing for Studying the Biotransformation of Hydrophobic Organic Chemicals: Microbial Degradation as an Example

DEFF Research Database (Denmark)

Smith, Kilian E. C.; Rein, Arno; Trapp, Stefan

2012-01-01

Biotransformation plays a key role in hydrophobic organic compound (HOC) fate, and understanding kinetics as a function of (bio)availability is critical for elucidating persistence, accumulation, and toxicity. Biotransformation mainly occurs in an aqueous environment, posing technical challenges...... for producing kinetic data because of low HOC solubilities and sorptive losses. To overcome these, a new experimental approach based on passive dosing is presented. This avoids using cosolvent for introducing the HOC substrate, buffers substrate depletion so biotransformation is measured within a narrow...... also similar for both PAHs, but decreased by around 2 orders of magnitude with increasing dissolved concentrations. Dynamic passive dosing is a useful tool for measuring biotransformation kinetics at realistically low and defined dissolved HOC concentrations....

Biotransformation and Incorporation into Proteins along a Simulated Terrestrial Food Chain

Energy Technology Data Exchange (ETDEWEB)

Unrine, J.M., B.P. Jackson and W.A. Hopkins

2007-01-01

Selenium is an essential trace element in vertebrates, but there is a narrow concentration range between dietary requirement and toxicity threshold. Although a great deal is known about the biochemistry of Se from a nutritional perspective, considerably less attention has been focused on the specific biochemistry of Se as an environmental toxicant. Recent advances in hyphenated analytical techniques have provided the capability of quantifying specific chemical forms of Se in biological tissues as well as the distribution of Se among macromolecules. We applied liquid chromatography coupled to inductively coupled plasma mass spectrometry to investigate biotransformations of selenomethionine along a simulated terrestrial food chain consisting of selenomethionine exposed crickets (Acheta domesticus) fed to western fence lizards (Sceloporus occidentalis). Evidence was obtained for selenomethionine biotransformation as well as for sex-specific differences in the metabolism of Se compounds and their subsequent incorporation into proteins in the lizard. The results demonstrate the complexities involved in trophic transfer of Se due to the potential for extensive biotransformation and the species- and even sex-specific nature of these biotransformations.

A new technique for promoting cyclic utilization of cyclodextrins in biotransformation.

Science.gov (United States)

Shen, Yanbing; Yu, Ziqi; Yang, Xu; Wang, Fang; Luo, Jianmei; Wang, Min

2017-01-01

Cyclodextrins (CDs) can improve the productivity of steroid biotransformation by enhancing substrate solubility. CDs can be recycled by grafting them with appropriate carriers. Loofah fiber is an excellent grafting material for CDs, and can be applied to the biotransformation and recycling of β-cyclodextrin (β-CD). In this work, a technique for recycling β-CD in cortisone acetate (CA) biotransformation by Arthrobacter simplex CPCC 140451 was studied. Loofah fiber-grafted β-CD (LF-β-CD) was prepared using epichlorohydrin, which is a cross-linking agent. The grafting yield of β-CD was 74.8 mg g -1 dried fibers. LF-β-CD could increase the solubility of CA and enhance biotransformation. The initial conversion rate of CA was 1.5-fold higher than that of the blank group. LF-β-CD was also used in biocatalytic reactions for eight cycles, and it maintained the conversion ratio of CA at approximately 90%. Given the above positive results, LF-β-CD can be utilized in biotechnological recycling applications. This method can also be applied to CD derivatives and hydrophobic compounds.

Estimation of biotransformation and sorption of emerging organic compounds (EOCs) during artificial recharge through a reactive barrier.

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Valhondo, C.; Martinez-Landa, L.; Carrera, J.; Hidalgo, J. J.; Ayora, C.

2016-12-01

The reuse of lesser quality water such as effluents from wastewater treatment plants or effluent-receiving water bodies has been promoted due to the water shortages affecting many regions of the world. Artificial recharge through infiltration basins is known to improve several water quality parameters including the attenuation of emerging organic compounds (EOCs). Many of these contaminants exhibit redox dependent biotransformation because the redox state is one of the factors controlling microbial community development. Together with biotransformation, sorption also affects the behavior of EOCs in their passage through the soil. We studied EOCs attenuation in an infiltration system is located in Sant Vicenç dells Horts on the Llobregat delta (Barcelona, Spain), where the local water agency has an artificial recharge pilot project . The Llobregat river water used for the artificial recharge is affected by treatment plant effluents which contain EOCs. A reactive barrier consisting of vegetable compost, clay, and iron oxide was installed in the bottom of the infiltration basin to enhance biotransformation and sorption of EOCs. The barrier releases dissolved organic carbon, which favors the development of a broad range of redox environments, and supplies neutral, cationic, and anionic surfaces to favor sorption of different types of contaminants. Results were excellent, but quantitative evaluation of the EOCs attenuation requires knowledge of the residence time distribution of infiltrated water. A tracer test was performed by adding tracers to the infiltration water and interpreting the breakthrough curves at diverse monitoring points with a 2D multilayer numerical model. The calibrated model quantify degradation, as a first order law, and sorption through a linear distribution coefficient for ten selected EOCs. Results indicate higher degradation rates and sorption coefficients in the reactive barrier than in the rest of the aquifer for nine and eight of the ten

Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

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Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

2013-01-01

Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

The Remarkable Structural Diversity Achieved in ent-Kaurane Diterpenes by Fungal Biotransformations

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Jacqueline A. Takahashi

2014-02-01

Full Text Available The use of biotransformations in organic chemistry is widespread, with highlights of interesting applications in the functionalization of natural products containing unactivated carbons, like the kaurane diterpenes. A number of compounds with kaurane skeletons can be isolated in large amounts from several plant species and a myriad of biological activities has been related to these compounds. Studies on structure versus activity have showed that, in most cases, in kaurane diterpenes, activity increases with the increase of functionalization. Since naturally occurring kaurane diterpenes usually have limited functional groups to be used as targets for semi-synthetic modifications, production of more polar derivatives from kaurane diterpenes have been achieved mostly through the use of fungal biotransformations. In this review, selected examples the wonderful chemical diversity produced by fungi in kaurane diterpenes is presented. This diversity includes mainly hydroxylation of nearly all carbon atoms of the kaurane molecule, many of them carried out stereoselectively, as well as ring rearrangements, among other chemical modifications. Sources of starting materials, general biotransformation protocols employed, fungi with most consistent regioselectivity towards kaurane skeleton, as well as biological activities associated with starting materials and products are also described.

Organohalogen Compounds in Pet Dog and Cat: Do Pets Biotransform Natural Brominated Products in Food to Harmful Hydroxlated Substances?

Science.gov (United States)

Mizukawa, Hazuki; Nomiyama, Kei; Nakatsu, Susumu; Iwata, Hisato; Yoo, Jean; Kubota, Akira; Yamamoto, Miyuki; Ishizuka, Mayumi; Ikenaka, Yoshinori; Nakayama, Shouta M M; Kunisue, Tatsuya; Tanabe, Shinsuke

2016-01-05

There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organohalogen contaminants and their hydroxylated metabolites. This study investigated the blood contaminants polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PCBs, OH-PBDEs, and MeO-PBDEs), in pet dogs and cats. We also measured the residue levels of these compounds in commercially available pet foods. Chemical analyses of PCBs and OH-PCBs showed that the OH-PCB levels were 1 to 2 orders of magnitude lower in cat and dog food products than in their blood, suggesting that the origin of OH-PCBs in pet dogs and cats is PCBs ingested with their food. The major congeners of OH-/MeO-PBDEs identified in both pet food products and blood were natural products (6OH-/MeO-BDE47 and 2'OH-/MeO-BDE68) from marine organisms. In particular, higher concentrations of 6OH-BDE47 than 2'OH-BDE68 and two MeO-PBDE congeners were observed in the cat blood, although MeO-BDEs were dominant in cat foods, suggesting the efficient biotransformation of 6OH-BDE47 from 6MeO-BDE47 in cats. We performed in vitro demethylation experiments to confirm the biotransformation of MeO-PBDEs to OH-PBDEs using liver microsomes. The results showed that 6MeO-BDE47 and 2'MeO-BDE68 were demethylated to 6OH-BDE47 and 2'OH-BDE68 in both animals, whereas no hydroxylated metabolite from BDE47 was detected. The present study suggests that pet cats are exposed to MeO-PBDEs through cat food products containing fish flavors and that the OH-PBDEs in cat blood are derived from the CYP-dependent demethylation of naturally occurring MeO-PBDE congeners, not from the hydroxylation of PBDEs.

Biotransformation of dichlorodiphenyltrichloroethane in the benthic polychaete, Nereis succinea: quantitative estimation by analyzing the partitioning of chemicals between gut fluid and lipid.

Science.gov (United States)

Wang, Fei; Pei, Yuan-yuan; You, Jing

2015-02-01

Biotransformation plays an important role in the bioaccumulation and toxicity of a chemical in biota. Dichlorodiphenyltrichloroethane (DDT) commonly co-occurs with its metabolites (dichlorodiphenyldichloroethane [DDD] and dichlorodiphenyldichloroethylene [DDE]), in the environment; thus it is a challenge to accurately quantify the biotransformation rates of DDT and distinguish the sources of the accumulated metabolites in an organism. The present study describes a method developed to quantitatively analyze the biotransformation of p,p'-DDT in the benthic polychaete, Nereis succinea. The lugworms were exposed to sediments spiked with DDT at various concentrations for 28 d. Degradation of DDT to DDD and DDE occurred in sediments during the aging period, and approximately two-thirds of the DDT remained in the sediment. To calculate the biotransformation rates, residues of individual compounds measured in the bioaccumulation testing (after biotransformation) were compared with residues predicted by analyzing the partitioning of the parent and metabolite compounds between gut fluid and tissue lipid (before biotransformation). The results suggest that sediment ingestion rates decreased when DDT concentrations in sediment increased. Extensive biotransformation of DDT occurred in N. succinea, with 86% of DDT being metabolized to DDD and biotransformation, and the remaining 30% was from direct uptake of sediment-associated DDD. In addition, the biotransformation was not dependent on bulk sediment concentrations, but rather on bioaccessible concentrations of the chemicals in sediment, which were quantified by gut fluid extraction. The newly established method improved the accuracy of prediction of the bioaccumulation and toxicity of DDTs. © 2014 SETAC.

Biotransformation of 20(S)-protopanaxatriol by Mucor racemosus and the anti-cancer activities of some products.

Science.gov (United States)

Chen, Guangtong; Ge, Hongjuan; Song, Yan; Li, Jianlin; Zhai, Xuguang; Wu, Juanjuan; Ling, Xiang

2015-10-01

To produce new derivatives of 20(S)-protopanaxatriol by fungal biotransformation. Biotransformation of 20(S)-protopanaxatriol (1) by Mucor racemosus AS 3.205 afforded six products. Their structures were elucidated on the basis of extensive spectroscopic analyses. M. racemosus could selectively catalyze dehydrogenation at C-12 and further hydroxylation at C-7, C-11, and C-15, as well as rearrangement of double bond at C-26. Two of these new compounds exhibited potent inhibitory activity against SH-SY5Y and HepG2 cell lines. Biotransformation by M. racemosus AS 3.205 was an effective approach to produce new derivatives of 20(S)-protopanaxatriol.

Biotransformação de limoneno: uma revisão das principais rotas metabólicas Biotransformation of limonene: a review of the main metabolic pathways

Directory of Open Access Journals (Sweden)

Mário Roberto Maróstica Júnior

2007-04-01

Full Text Available There is considerable progress in the study of the biotransformation of limonene. Extensive research on the biotransformation of limonene has resulted in the elucidation of new metabolic pathways. Natural flavors can be produced via biotransformation, satisfying consumer demand for natural products. This review presents some elements concerning the biotransformation of limonene with emphasis on the metabolic pathways. Some comments are also made on problems related to biocatalysis as well as on the application of some compounds originating from the biotransformation of the inexpensive limonene.

Biotransformation of (+)-isofraxinellone by Aspergillus niger and insect antifeedant activity.

Science.gov (United States)

Okuno, Yoshiharu; Marumoto, Shinsuke; Tsurumi, Jun; Miyazawa, Mitsuo

2018-01-24

The biotransformation of (+)-isofraxinellone (1) by Aspergillus niger was investigated. Compound 1 was transformed to only one new compound 2. The structure of 2 was identified as (-)-(4S)-4-hydroxyisofraxinellone which was regio- and stereo-selective hydroxylated at the C-4 position by IR, EI-MS 1D and 2D NMR. Absolute configuration of hydroxyl group at the C-4 position was detected by modified Mosher's method. Antifeedant activity of compounds 1 and 2 against larvae of Spodoptera litura was assayed. These compounds showed potent antifeedant activity and ED 50 (50% of effective dose) values were 3.91 and 4.43 μg/cm 2 , respectively.

(Bio)transformation of 2,4-dinitroanisole (DNAN) in soils

Energy Technology Data Exchange (ETDEWEB)

Olivares, Christopher I., E-mail: olivarec@email.arizona.edu [Department of Chemical and Environmental Engineering, University of Arizona, P.O. Box 210011, Tucson, AZ 85721 (United States); Abrell, Leif [Department of Soil, Water & Environmental Science, University of Arizona, P.O. Box 210011, Tucson, AZ 85721 (United States); Department of Chemistry & Biochemistry, University of Arizona, P.O. Box 210011, Tucson, AZ 85721 (United States); Khatiwada, Raju; Chorover, Jon [Department of Soil, Water & Environmental Science, University of Arizona, P.O. Box 210011, Tucson, AZ 85721 (United States); Sierra-Alvarez, Reyes; Field, Jim A. [Department of Chemical and Environmental Engineering, University of Arizona, P.O. Box 210011, Tucson, AZ 85721 (United States)

2016-03-05

Highlights: • DNAN anaerobic transformation was faster than aerobic conversion. • Anaerobic DNAN conversion rate correlated well with soil organic carbon (≤2.07%). • H{sub 2} added as electron donor enhanced DNAN biotransformation. • DNAN nitroreduction lead to monomer products which coupled to form azo dimers. • Anaerobic transformation pathway and azo dimer formation mechanism were proposed. - Abstract: Recent studies have begun to assess the environmental fate and toxicity of 2,4-dinitroanisole (DNAN), an insensitive munition compound of interest to defense agencies. Aerobic and anaerobic DNAN biotransformation in soils was evaluated in this study. Under aerobic conditions, there was little evidence of transformation; most observed removal was attributed to adsorption and subsequent slow chemical reactions. Under anaerobic conditions, DNAN was reductively (bio)transformed and the rate of the transformation was positively correlated with soil organic carbon (OC) up to a threshold of 2.07% OC. H{sub 2} addition enhanced the nitroreduction rate compared to endogenous treatments lacking H{sub 2}. Heat-killed treatments provided rates similar to the endogenous treatment, suggesting that abiotic factors play a role in DNAN reduction. Ten (bio)transformation products were detected by high-resolution mass spectrometry. The proposed transformation pathway involves reduction of DNAN to aromatic amines, with putative reactive nitroso-intermediates coupling with the amines to form azo dimers. Secondary reactions include N-alkyl substitution, O-demethylation (sometimes followed by dehydroxylation), and removal of an N-containing group. Globally, our results suggest that the main reaction DNAN undergoes in anaerobic soils is nitroreduction to 2-methoxy-5-nitroaniline (MENA) and 2,4-diaminoanisole (DAAN), followed by anaerobic coupling reactions yielding azo-dimers. The dimers were subsequently subject to further (bio)transformations.

Characterization of biotransformation enzyme activities in primary rat proximal tubular cells

NARCIS (Netherlands)

Schaaf, G.; de Groene, E.M.; Maas, R.; Commandeur, J.N.M.; Fink-Gremmels, J.

2001-01-01

The proximal tubule is a frequent target for nephrotoxic compounds due to it's ability to transport and accumulate xenobiotics and their metabolites, as well as by the presence of an organ-selective set of biotransformation enzymes. The aim of the present study was to characterize the activities of

A field experiment for the anaerobic biotransformation of aromatic hydrocarbon compounds at Seal Beach, California

International Nuclear Information System (INIS)

Reinhard, M.; Wills, L.E.; Ball, H.A.; Harmon, T.

1991-01-01

Biotransformation of aromatic hydrocarbons under anaerobic conditions is of interest because dissolved oxygen is rapidly consumed in groundwater contaminant plumes of hydrocarbon fuel. Anaerobic biotransformation of aromatic hydrocarbons has been demonstrated under different redox regimes including nitrate-reducing iron-reducing and fermentative-methanogenic conditions. Recently, laboratory evidence has been obtained for the degradation of alkylbenzenes including toluene under sulfate-reducing conditions. The long-term objective of this study is to determine transformation rates under the conditions of the Seal Beach site, and second to explore the feasibility of inducing nitrate- and sulfate-reducing conditions and fermentative-methanogenic conditions in field bioreactors. Both laboratory studies and field studies in bioreactors are being conducted. This paper reports on the experimental design of the bioreactors and initial results

Biotransformation of nitrogen- and sulfur-containing pollutants during coking wastewater treatment: Correspondence of performance to microbial community functional structure.

Science.gov (United States)

Joshi, Dev Raj; Zhang, Yu; Gao, Yinxin; Liu, Yuan; Yang, Min

2017-09-15

Although coking wastewater is generally considered to contain high concentration of nitrogen- and sulfur-containing pollutants, the biotransformation processes of these compounds have not been well understood. Herein, a high throughput functional gene array (GeoChip 5.0) in combination with Illumina MiSeq sequencing of the 16S rRNA gene were used to identify microbial functional traits and their role in biotransformation of nitrogen- and sulfur-containing compounds in a bench-scale aerobic coking wastewater treatment system operated for 488 days. Biotransformation of nitrogen and sulfur-containing pollutants deteriorated when pH of the bioreactor was increased to >8.0, and the microbial community functional structure was significantly associated with pH (Mantels test, P functional microbial community structure (P functional genes for biotransformation of nitrogen- and sulfur-containing pollutants. Functional characterization of taxa and network analysis suggested that Burkholderiales, Actinomycetales, Rhizobiales, Pseudomonadales, and Hydrogenophiliales (Thiobacillus) were key functional taxa. Variance partitioning analysis showed that pH and influent ammonia nitrogen jointly explained 25.9% and 35.5% of variation in organic pollutant degrading genes and microbial community structure, respectively. This study revealed a linkage between microbial community functional structure and the likely biotransformation of nitrogen- and sulfur-containing pollutants, along with a suitable range of pH (7.0-7.5) for stability of the biological system treating coking wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phenolic biotransformations during conversion of ferulic acid to vanillin by lactic acid bacteria.

Science.gov (United States)

Kaur, Baljinder; Chakraborty, Debkumar; Kumar, Balvir

2013-01-01

Vanillin is widely used as food additive and as a masking agent in various pharmaceutical formulations. Ferulic acid is an important precursor of vanillin that is available in abundance in cell walls of cereals like wheat, corn, and rice. Phenolic biotransformations can occur during growth of lactic acid bacteria (LAB), and their production can be made feasible using specialized LAB strains that have been reported to produce ferulic acid esterases. The present study aimed at screening a panel of LAB isolates for their ability to release phenolics from agrowaste materials like rice bran and their biotransformation to industrially important compounds such as ferulic acid, 4-ethyl phenol, vanillic acid, vanillin, and vanillyl alcohol. Bacterial isolates were evaluated using ferulic acid esterase, ferulic acid decarboxylase, and vanillin dehydrogenase assays. This work highlights the importance of lactic acid bacteria in phenolic biotransformations for the development of food grade flavours and additives.

Phenolic Biotransformations during Conversion of Ferulic Acid to Vanillin by Lactic Acid Bacteria

Science.gov (United States)

Kaur, Baljinder; Kumar, Balvir

2013-01-01

Vanillin is widely used as food additive and as a masking agent in various pharmaceutical formulations. Ferulic acid is an important precursor of vanillin that is available in abundance in cell walls of cereals like wheat, corn, and rice. Phenolic biotransformations can occur during growth of lactic acid bacteria (LAB), and their production can be made feasible using specialized LAB strains that have been reported to produce ferulic acid esterases. The present study aimed at screening a panel of LAB isolates for their ability to release phenolics from agrowaste materials like rice bran and their biotransformation to industrially important compounds such as ferulic acid, 4-ethyl phenol, vanillic acid, vanillin, and vanillyl alcohol. Bacterial isolates were evaluated using ferulic acid esterase, ferulic acid decarboxylase, and vanillin dehydrogenase assays. This work highlights the importance of lactic acid bacteria in phenolic biotransformations for the development of food grade flavours and additives. PMID:24066293

Enantioselective biotransformations of nitriles in organic synthesis.

Science.gov (United States)

Wang, Mei-Xiang

2015-03-17

The hydration and hydrolysis of nitriles are valuable synthetic methods used to prepare carboxamides and carboxylic acids. However, chemical hydration and hydrolysis of nitriles involve harsh reaction conditions, have low selectivity, and generate large amounts of waste. Therefore, researchers have confined the scope of these reactions to simple nitrile substrates. However, biological transformations of nitriles are highly efficient, chemoselective, and environmentally benign, which has led synthetic organic chemists and biotechologists to study these reactions in detail over the last two decades. In nature, biological systems degrade nitriles via two distinct pathways: nitrilases catalyze the direct hydrolysis of nitriles to afford carboxylic acids with release of ammonia, and nitrile hydratases catalyze the conversion of nitriles into carboxamides, which then furnish carboxylic acids via hydrolysis in the presence of amidases. Researchers have subsequently developed biocatalytic methods into useful industrial processes for the manufacture of commodity chemicals, including acrylamide. Since the late 1990s, research by my group and others has led to enormous progress in the understanding and application of enantioselective biotransformations of nitriles in organic synthesis. In this Account, I summarize the important advances in enantioselective biotransformations of nitriles and amides, with a primary focus on research from my laboratory. I describe microbial whole-cell-catalyzed kinetic resolution of various functionalized nitriles, amino- and hydroxynitriles, and nitriles that contain small rings and the desymmetrization of prochiral and meso dinitriles and diamides. I also demonstrate how we can apply the biocatalytic protocol to synthesize natural products and bioactive compounds. These nitrile biotransformations offer an attractive and unique protocol for the enantioselective synthesis of polyfunctionalized organic compounds that are not readily obtainable by

Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil.

Science.gov (United States)

Liu, Chen; Liu, Jinxia

2016-05-01

Microbial transformation of polyfluoroalkyl phosphate esters (PAPs) into perfluorocarboxylic acids (PFCAs) has recently been confirmed to occur in activated sludge and soil. However, there lacks quantitative information about the half-lives of the PAPs and their significance as the precursors to PFCAs. In the present study, the biotransformation of 6:2 and 8:2 diPAP in aerobic soil was investigated in semi-dynamics reactors using improved sample preparation methods. To develop an efficient extraction method for PAPs, six different extraction solvents were compared, and the phenomenon of solvent-enhanced hydrolysis was investigated. It was found that adding acetic acid could enhance the recoveries of the diPAPs and inhibit undesirable hydrolysis during solvent extraction of soil. However 6:2 and 8:2 monoPAPs, which are the first breakdown products from diPAPs, were found to be unstable in the six solvents tested and quickly hydrolyzed to form fluorotelomer alcohols. Therefore reliable measurement of the monoPAPs from a live soil was not achievable. The apparent DT50 values of 6:2 diPAP and 8:2 diPAP biotransformation were estimated to be 12 and > 1000 days, respectively, using a double first-order in parallel model. At the end of incubation of day 112, the major degradation products of 6:2 diPAP were 5:3 fluorotelomer carboxylic acid (5:3 acid, 9.3% by mole), perfluoropentanoic acid (PFPeA, 6.4%) and perfluorohexanoic acid (PFHxA, 6.0%). The primary product of 8:2 diPAP was perfluorooctanoic acid (PFOA, 2.1%). The approximately linear relationship between the half-lives of eleven polyfluoroalkyl and perfluoroalkyl substances (PFASs, including 6:2 and 8:2 diPAPs) that biotransform in aerobic soils and their molecular weights suggested that the molecular weight is a good indicator of the general stability of low-molecular-weight PFAS-based compounds in aerobic soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biotransformation of isofraxetin-6-O-β-d-glucopyranoside by Angelica sinensis (Oliv.) Diels callus.

Science.gov (United States)

Zhou, Di; Zhang, Yuhua; Jiang, Zhe; Hou, Yue; Jiao, Kun; Yan, Chunyan; Li, Ning

2017-01-15

Isofraxetin-6-O-β-d-glucopyranoside, identified from traditional medicinal herbal Xanthoceras sorbifolia Bunge, has been demonstrated to be a natural neuroinflammatory inhibitor. In order to obtain more derivatives with potential anti-neuroinflammatory effects, biotransformation was carried out. According to the characteristics of coumarin skeleton, suspension cultures of Angelica sinensis (Oliv.) Diels callus (A. sinensis callus) were employed because of the presence of diverse phenylpropanoids biosynthetic enzymes. As a result, 15 products were yielded from the suspension cultures, including a new coumarin: 8'-dehydroxymethyl cleomiscosin A (1), together with 14 known compounds. Their structures were elucidated by extensive spectroscopic analysis. Furthermore, the biotransformed pathways were discussed. Among them, compound 13 was transformed from isofraxetin-6-O-β-d-glucopyranoside, while compounds 1-6, 10-12, 14-15 were derived from the culture medium stimulated by the substrate. The biotransformation processes include hydroxylation, oxidation and esterification. Furthermore, their inhibitory effects on lipopolysaccharide (LPS)-activated nitric oxide (NO) production were evaluated in BV2 microglial cells. It is worth noting that, 1, 1'-methanediylbis(4-methoxybenzene) (3), obtucarbamates A (5), 2-nonyl-4-hydroxyquinoline N-oxide (10) and 1H-indole-3-carbaldehyde (11) exhibited significant inhibitory effect against neuroinflammation with IC 50 values at 1.22, 10.57, 1.02 and 0.76μM respectively, much stronger than that of the positive control minocycline (IC 50 35.82μM). Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased Yield of Biotransformation of Androsta-1, 4-Dien-3, 17-Dione from Β-Sitosterol by Using Sulfobutyl Ether-Β-Cyclodextrin Complexation Technique

Directory of Open Access Journals (Sweden)

Wang Jingwen

2016-01-01

Full Text Available Substrate solubility in steroid biotransformation is critical for enhancing the biotransformation of hydrophobic compounds. In this study, the sulfobutyl ether-β-cyclodextrin (SBE-β-CD complexation technique was used for the biotransformation of β-sitosterol to androsta-1, 4-diene-3, 17-dione with Mycobacterium ATCC25795. The production yield was increased by 26.72%, and the biotransformation course was shortened by 24h using β-sitosterol/SBE-β-CD inclusion complexes as substrates (1.0 g/L. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that an inclusion complex was formed between SBE-β-CD and β-sitosterol. The complex significantly increased the solubility of β-sitosterol and improved the biotransformation efficiency of the substrate.

Phenolic Biotransformations during Conversion of Ferulic Acid to Vanillin by Lactic Acid Bacteria

Directory of Open Access Journals (Sweden)

Baljinder Kaur

2013-01-01

Full Text Available Vanillin is widely used as food additive and as a masking agent in various pharmaceutical formulations. Ferulic acid is an important precursor of vanillin that is available in abundance in cell walls of cereals like wheat, corn, and rice. Phenolic biotransformations can occur during growth of lactic acid bacteria (LAB, and their production can be made feasible using specialized LAB strains that have been reported to produce ferulic acid esterases. The present study aimed at screening a panel of LAB isolates for their ability to release phenolics from agrowaste materials like rice bran and their biotransformation to industrially important compounds such as ferulic acid, 4-ethyl phenol, vanillic acid, vanillin, and vanillyl alcohol. Bacterial isolates were evaluated using ferulic acid esterase, ferulic acid decarboxylase, and vanillin dehydrogenase assays. This work highlights the importance of lactic acid bacteria in phenolic biotransformations for the development of food grade flavours and additives.

Evaluation of Predicted and Observed Data on Biotransformation of Twenty-Nine Trace Organic Chemicals

KAUST Repository

Bertolini, Maria

2011-07-01

Trace organic chemicals present in household products, pesticides, pharmaceuticals and personal care products may have adverse ecotoxicological effects once they are released to the environment. These chemicals are usually transported with the sewage to wastewater treatment facilities, where they might be attenuated depending on the degree of treatment applied prior to discharge to receiving streams. This study evaluates the removal performance of 29 trace organic compounds during two different activated sludge treatment systems. Predominant attenuation processes such as biotransformation and sorption for the target compounds were identified. Biotransformation rate constants determined in this study were used to assess removal of compounds from other treatment plants with similar operational conditions, using data gathered from the literature. The commercial software Catalogic was applied to predict environmental fate of chemicals. The software program consisted of four models able to simulate molecular transformations and to generate degradation trees. In order to assess the accuracy of this program in predicting biotransformation, one biodegradation model is used to contrast predicted degradation pathway with metabolic pathways reported in the literature. The predicted outcome was correct for more than 40 percent of the 29 targeted substances, while 38 percent of the chemicals exhibited some degree of lower agreement between predicted and observed pathways. Percent removal data determined for the two treatment facilities was compared with transformation probability output from Catalogic. About 80 percent of the 29 compounds exhibited a good correlation between probability of transformation of the parent compound and percent removal data from the two treatment plants (R2 = 0.82 and 0.9). Based upon findings for 29 trace organic chemicals regarding removal during activated sludge treatment, attacked fragments present in their structures, predicted data from

Quantitative structure activity relationships for the biotransformation and toxicity of halogenated benzene - derivatives : implications for enzyme catalysis and reaction mechanisms

NARCIS (Netherlands)

Cnubben, N.H.P.

1996-01-01

Organisms are frequently exposed to low molecular weight xenobiotic compounds. An advanced enzymatic machinery modifies these compounds into more hydrophilic metabolites which are subsequently excreted from the body. This process of biotransformation aims to detoxify bodyforeign

Biotransformation and bioactivation reactions of alicyclic amines in drug molecules.

Science.gov (United States)

Bolleddula, Jayaprakasam; DeMent, Kevin; Driscoll, James P; Worboys, Philip; Brassil, Patrick J; Bourdet, David L

2014-08-01

Aliphatic nitrogen heterocycles such as piperazine, piperidine, pyrrolidine, morpholine, aziridine, azetidine, and azepane are well known building blocks in drug design and important core structures in approved drug therapies. These core units have been targets for metabolic attack by P450s and other drug metabolizing enzymes such as aldehyde oxidase and monoamine oxidase (MAOs). The electron rich nitrogen and/or α-carbons are often major sites of metabolism of alicyclic amines. The most common biotransformations include N-oxidation, N-conjugation, oxidative N-dealkylation, ring oxidation, and ring opening. In some instances, the metabolic pathways generate electrophilic reactive intermediates and cause bioactivation. However, potential bioactivation related adverse events can be attenuated by structural modifications. Hence it is important to understand the biotransformation pathways to design stable drug candidates that are devoid of metabolic liabilities early in the discovery stage. The current review provides a comprehensive summary of biotransformation and bioactivation pathways of aliphatic nitrogen containing heterocycles and strategies to mitigate metabolic liabilities.

Biotransformation of citrus aromatics nootkatone and valencene by microorganisms.

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Furusawa, Mai; Hashimoto, Toshihiro; Noma, Yoshiaki; Asakawa, Yoshinori

2005-11-01

Biotransformations of the sesquiterpene ketone nootkatone from the crude drug Alpiniae Fructus and grapefruit oil, and the sesquiterpene hydrocarbon valencene from Valencia orange oil were carried out with microorganisms such as Aspergillus niger, Botryosphaeria dothidea, and Fusarium culmorum to afford structurally interesting metabolites. Their stereostructures were established by a combination of high-resolution NMR spectral and X-ray crystallographic analysis and chemical reaction. Metabolic pathways of compounds and by A. niger are proposed.

Expanding the chemical space for natural products by Aspergillus-Streptomyces co-cultivation and biotransformation

Science.gov (United States)

Wu, Changsheng; Zacchetti, Boris; Ram, Arthur F.J.; van Wezel, Gilles P.; Claessen, Dennis; Hae Choi, Young

2015-01-01

Actinomycetes and filamentous fungi produce a wide range of bioactive compounds, with applications as antimicrobials, anticancer agents or agrochemicals. Their genomes contain a far larger number of gene clusters for natural products than originally anticipated, and novel approaches are required to exploit this potential reservoir of new drugs. Here, we show that co-cultivation of the filamentous model microbes Streptomyces coelicolor and Aspergillus niger has a major impact on their secondary metabolism. NMR-based metabolomics combined with multivariate data analysis revealed several compounds that correlated specifically to co-cultures, including the cyclic dipeptide cyclo(Phe-Phe) and 2-hydroxyphenylacetic acid, both of which were produced by A. niger in response to S. coelicolor. Furthermore, biotransformation studies with o-coumaric acid and caffeic acid resulted in the production of the novel compounds (E)-2-(3-hydroxyprop-1-en-1-yl)-phenol and (2E,4E)-3-(2-carboxy-1-hydroxyethyl)-2,4-hexadienedioxic acid, respectively. This highlights the utility of microbial co-cultivation combined with NMR-based metabolomics as an efficient pipeline for the discovery of novel natural products. PMID:26040782

Vanillin production by biotransformation of phenolic compounds in fungus, Aspergillus luchuensis.

Science.gov (United States)

Taira, Junsei; Toyoshima, Rin; Ameku, Nana; Iguchi, Akira; Tamaki, Yasutomo

2018-03-13

Vanillin is valuable and popular flavor used in foods and cosmetics. Many bacteria species have the ability to decarboxylate substituted cinnamic acids in order to form vanillin. However, the phenolic biotransformation including vanillin production in a common fungus, the Aspergillus luchuensis, which is used in distilled beverages, has not yet been clarified. This study focused on elucidating the vanillin production due to phenolic biotransformation in A. luchuensis during fermentation. The phenolic metabolites were extracted by a solid phase column and they were determined using on LC/MS and LC/MS/MS in a selective ion mode. As a result, ferulic acid, vanillin and vanillic acid, were detected in the rice koji fermentationed by A. luchuensis and also fermentated with yeast. In addition, the accurate molecular formula of vanillin glucoside (C 14 H 17 O 8 , 313.0927, (M-H) - and its production ions was also determined by HRESI-mass spectrometry. Based on the results including the phenolic metabolites and related genes found in A. luchuensis genome, this study proposed the vanillin production mechanism due to the side chain cleavage of ferulic acid through Coenzyme A (CoA) and feruloyl-CoA hydratase/lyase, to form vanillin and acetyl-COA. In this study, another possible vanillin production pathway also was proposed due to the neutral hexose hydrolysis of vanillin glucoside. The subsequent dehydrogenation of vanillin produced vanillic acid. In addition, vanillin was detected in the distilled alcohol indicating its contribution to the aroma profile of beverages. It has been unknown that the vanillin in the distilled solution is derived from the vanillin produced during rice-koji and/or moromi mash fermentations.

Biotransformation of Food Dyes by Human Intestinal Bacteria ...

African Journals Online (AJOL)

Biotransformation of food dyes (Tartrazine and Quinoline yellow) by Streptococcus faecalis and Escherichia coli isolated from human intestinal microflora was investigated. Decolourisation of the media containing the dyes was used as an index of biotransformation. Biotransformation was higher under aerobic than under ...

Lipases and whole cell biotransformations of 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid and its ester.

Science.gov (United States)

Majewska, Paulina; Serafin, Monika; Klimek-Ochab, Magdalena; Brzezińska-Rodak, Małgorzata; Żymańczyk-Duda, Ewa

2016-06-01

A wide spectrum of commercially available lipases and microbial whole cells catalysts were tested for biotransformations of 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid 1 and its butyryl ester. The best results were achieved for biocatalytic hydrolysis of ester: 2-butyryloxy-2-(ethoxyphenylphosphinyl)acetic acid 2 performed by lipase from Candida cylindracea, what gave optically active products with 85% enantiomeric excess, 50% conversion degree and enantioselectivity 32.9 for one pair of enantiomers. Also enzymatic systems of Penicillium minioluteum and Fusarium oxysporum were able to hydrolyze tested compound with high enantiomeric excess (68-93% ee), enantioselectivity (44 for one pair of enantiomers) and conversion degree about 50-55%. Enzymatic acylation of hydroxyphosphinate was successful in case when porcine pancreas lipase was used. After 4days of biotransformation the conversion reaches 45% but the enantiomeric enrichment of the isomers mixture do not exceed 43%. Obtained chiral compounds are valuable derivatizing agents for spectroscopic (NMR) evaluation of enantiomeric excess for particular compounds (e.g. amino acids). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Organometallic compounds in the environment

National Research Council Canada - National Science Library

Craig, P. J

2003-01-01

... of Organometallic Species in the Environment 20 1.10 Stability of Organometallic Compounds in Biological Systems 1.11 G eneral Comments on the Toxicities of Organometallic Compounds 22 1.12 General Considerations on Environmental R eactivity of Organometallic Compounds 24 1.13 Microbial Biotransformation of Metals and M etalloids 25 1.13.1 Introduction 25 1...

Biotransformation of bergapten and xanthotoxin by Glomerella cingulata.

Science.gov (United States)

Marumoto, Shinsuke; Miyazawa, Mitsuo

2010-07-14

The biotransformation of bergapten (1) by the fungus Glomerella cingulata gave the corresponding reduced acid, 6,7-furano-5-methoxy hydrocoumaric acid (2), a new compound. Xanthotoxin (3) was also converted to the corresponding reduced acid cnidiol b (4) and demethylated metabolite xanthotoxol (5) by G. cingulata. The structure of the new compound 2 was elucidated by high-resolution mass spectrometry, extensive NMR techniques, including (1)H NMR and (13)C NMR, (1)H-(1)H correlation spectroscopy, heteronuclear multiple quantum coherence, and heteonuclear multiple bond coherence. The methyl ester or methyl ether or methyl ester and ether derivatives of 2 and 4 were synthesized. All compounds were tested for the beta-secretase (BACE1) inhibitory activity in vitro. The methyl ester and ether derivative 8 was shown to possess BACE1 inhibitory activity, and a IC(50) value was 0.64 +/- 0.04 mM.

Microbial Biotransformation to Obtain New Antifungals

Science.gov (United States)

Bianchini, Luiz F.; Arruda, Maria F. C.; Vieira, Sergio R.; Campelo, Patrícia M. S.; Grégio, Ana M. T.; Rosa, Edvaldo A. R.

2015-01-01

Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called “green chemistry,” which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact. PMID:26733974

Biotransformation of mercury in pH-stat cultures of eukaryotic freshwater algae.

Science.gov (United States)

Kelly, David J A; Budd, Kenneth; Lefebvre, Daniel D

2007-01-01

Eukaryotic algae were studied to determine their ability to biotransform Hg(II) under aerated and pH controlled conditions. All algae converted Hg(II) into beta-HgS and Hg(0) to varying degrees. When Hg(II) was administered as HgCl(2) to the algae, biotransformation by species of Chlorophyceae (Selenastrum minutum and Chlorella fusca var. fusca) was initiated with beta-HgS synthesis (K (1/2) of hours) and concomitant Hg degrees evolution occurred in the first hour. Hg degrees synthesis was impeded by the formation of beta-HgS and this inhibition was released in C. fusca var. fusca when cellular thiols were oxidized by the addition of dimethylfumarate (DMF). The diatom, Navicula pelliculosa (Bacillariophyceae), converted a substantially greater proportion of the applied Hg(II) into Hg(0), whereas the thermophilic alga, Galdieria sulphuraria (Cyanidiophyceae), rapidly biotransformed as much as 90% of applied Hg(II) into beta-HgS (K (1/2) approximately 20 min). This thermophile was also able to generate Hg(0) even after all exogenously applied HgCl(2) had been biotransformed. The results suggest that beta-HgS may be the major dietary mercurial for grazers of contaminated eukaryotic algae.

Bio-transformation of selenium in Se-enriched bacterial strains of Lactobacillus casei.

Science.gov (United States)

Kurek, Eliza; Ruszczyńska, Anna; Wojciechowski, Marcin; Łuciuk, Anna; Michalska-Kacymirow, Magdalena; Motyl, Ilona; Bulska, Ewa

Selenium is an element of very great importance for the proper functioning of the human body, mainly due to its antioxidant properties. Selenium exhibits a preventive effect in the case of cardiovascular disease, the immune system, male infertility and inhibits the toxic action of other agents. Selenium is important for Hashimoto's disease. Intake of selenium in the diet slows the aging process. The biological and toxicological effects of selenium strongly depend on its chemical form. Some organisms for example: plant, yeast, are capable of metabolizing low bioavailable selenium compounds (inorganic selenium) into its high bioavailable forms (organic selenium). The aim of this study was to investigate the bio-transformation of selenium by Lactobacillus bacteria towards the characterisation of selenium metabolites. The speciation of selenium was evaluated by high performance liquid chromatography with inductively coupled plasma mass spectrometry detector. The extraction of selenium species from lyophilized bacteria was executed with water, the mixture of lipase and protease, as well as lisozyme and sodium dodecyl sulphate. All investigated bacteria strains cultivated in the presence of Na2SeO3 effectively uptake selenium. Surprisingly, none of the applied extraction media exhibited a strong power to release the majority of the uptaken selenium compounds. Thus a maximum of 10% of the selenium was extracted from bacteria exposed to the enzymes. However, it was found that Lactobacillus bacteria are able to metabolize inorganic ions of selenium (IV) into Se-methionine, Se-methyloselenocysteine and other unidentified forms. The study confirmed the ability of probiotic bacteria to biotransform inorganic selenium into its organic derivatives. Therefore, Se-enriched bacteria can be considered as an addition to the functional food. selenium speciation, extraction procedure, Lactobacillus casei bacteria, Lactic acid bacteria (LAB), HPLC ICP-MS, functional food.

Studies on the Diels-Alder adduct from cyclopentadiene and p-benzoquinone: Biotransformation, enantiomeric excess and absolute configuration

Directory of Open Access Journals (Sweden)

Felipe Camargo Braga

2012-06-01

Full Text Available The use of microorganisms or isolated enzymes in synthetic routes has been extensively used by industry and academic research. A great advantage of biotransformation in a synthetic route is highly regio- and enatiosselective control, which can be achieved through microbial catalyzed reaction. Biotransformation is one of the most efficient methods in a production of high purity optical compounds and development of efficient routes for target molecules. Biotransformation by Mucor ramosissimus of enedione 1 gave the keto-alcohol (--2 with enantiomeric excess (ee>99,9% (determined by 1H NMR with [(+-Eu(hfc]3 and their epimer (--3. Determination of the absolute configuration of epimer (--3 was accomplished by controlled reaction and measuring of optical rotation (scheme 1. The fungus M. ramosissimus is a promising species to perform desymmetrization of diketones with high enantioselectivity.

Somatic and gastrointestinal in vivo biotransformation rates of hydrophobic chemicals in fish.

Science.gov (United States)

Lo, Justin C; Campbell, David A; Kennedy, Christopher J; Gobas, Frank A P C

2015-10-01

To improve current bioaccumulation assessment methods, a methodology is developed, applied, and investigated for measuring in vivo biotransformation rates of hydrophobic organic substances in the body (soma) and gastrointestinal tract of the fish. The method resembles the Organisation for Economic Co-operation and Development (OECD) 305 dietary bioaccumulation test but includes reference chemicals to determine both somatic and gastrointestinal biotransformation rates of test chemicals. Somatic biotransformation rate constants for the test chemicals ranged between 0 d(-1) and 0.38 (standard error [SE] 0.03)/d(-1) . Gastrointestinal biotransformation rate constants varied from 0 d(-1) to 46 (SE 7) d(-1) . Gastrointestinal biotransformation contributed more to the overall biotransformation in fish than somatic biotransformation for all test substances but 1. Results suggest that biomagnification tests can reveal the full extent of biotransformation in fish. The common presumption that the liver is the main site of biotransformation may not apply to many substances exposed through the diet. The results suggest that the application of quantitative structure-activity relationships (QSARs) for somatic biotransformation rates and hepatic in vitro models to assess the effect of biotransformation on bioaccumulation can underestimate biotransformation rates and overestimate the biomagnification potential of chemicals that are biotransformed in the gastrointestinal tract. With some modifications, the OECD 305 test can generate somatic and gastrointestinal biotransformation data to develop biotransformation QSARs and test in vitro-in vivo biotransformation extrapolation methods. © 2015 SETAC.

Silica ecosystem for synergistic biotransformation

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Mutlu, Baris R.; Sakkos, Jonathan K.; Yeom, Sujin; Wackett, Lawrence P.; Aksan, Alptekin

2016-06-01

Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues, we designed and produced a synthetic ecosystem by co-encapsulation in a silica gel matrix, which enabled precise control of the microbial populations and their microenvironment. As a case study, two greatly different microorganisms: Pseudomonas sp. NCIB 9816 and Synechococcus elongatus PCC 7942 were encapsulated. NCIB 9816 can aerobically biotransform over 100 aromatic hydrocarbons, a feat useful for synthesis of higher value commodity chemicals or environmental remediation. In our system, NCIB 9816 was used for biotransformation of naphthalene (a model substrate) into CO2 and the cyanobacterium PCC 7942 was used to provide the necessary oxygen for the biotransformation reactions via photosynthesis. A mathematical model was constructed to determine the critical cell density parameter to maximize oxygen production, and was then used to maximize the biotransformation rate of the system.

Production of human milk oligosaccharides by enzymatic and whole-cell microbial biotransformations.

Science.gov (United States)

Sprenger, Georg A; Baumgärtner, Florian; Albermann, Christoph

2017-09-20

Human milk oligosaccharides (HMO) are almost unique constituents of breast milk and are not found in appreciable amounts in cow milk. Due to several positive aspects of HMO for the development, health, and wellbeing of infants, production of HMO would be desirable. As a result, scientists from different disciplines have developed methods for the preparation of single HMO compounds. Here, we review approaches to HMO preparation by (chemo-)enzymatic syntheses or by whole-cell biotransformation with recombinant bacterial cells. With lactose as acceptor (in vitro or in vivo), fucosyltransferases can be used for the production of 2'-fucosyllactose, 3-fucosyllactose, or more complex fucosylated core structures. Sialylated HMO can be produced by sialyltransferases and trans-sialidases. Core structures as lacto-N-tetraose can be obtained by glycosyltransferases from chemical donor compounds or by multi-enzyme cascades; recent publications also show production of lacto-N-tetraose by recombinant Escherichia coli bacteria and approaches to obtain fucosylated core structures. In view of an industrial production of HMOs, the whole cell biotransformation is at this stage the most promising option to provide human milk oligosaccharides as food additive. Copyright © 2017 Elsevier B.V. All rights reserved.

Endophytic fungi as models for the stereoselective biotransformation of thioridazine.

Science.gov (United States)

Borges, Keyller Bastos; Borges, Warley De Souza; Pupo, Mônica Tallarico; Bonato, Pierina Sueli

2007-12-01

The stereoselective kinetic biotransformation of thioridazine, a phenothiazine neuroleptic drug, by endophytic fungi was investigated. In general, the sulfur of lateral chain (position 2) or the sulfur of phenothiazinic ring (position 5) were oxidated yielding the major human metabolites thioridazine-2-sulfoxide and thioridazine-5-sulfoxide. The quantity of metabolites biosynthesized varied among the 12 endophytic fungi evaluated. However, mono-2-sulfoxidation occurred in higher ratio and frequency. Among the 12 fungi evaluated, 4 of them deserve prominence for presenting an evidenced stereoselective biotransformation: Phomopsis sp. (TD2), Glomerella cingulata (VA1), Diaporthe phaseolorum (VR4), and Aspergillus fumigatus (VR12). Both enantiomers of thioridazine were consumed by the fungi; however, the 2-sulfoxidation yielded preferentially the R configuration at the sulfur atom.

Vigna radiata as a New Source for Biotransformation of Hydroquinone to Arbutin

Directory of Open Access Journals (Sweden)

Zahra Tofighi, Mohsen Amini, Mahzad Shirzadi, Hamideh Mirhabibi, Negar Ghazi Saeedi, Narguess Yassa

2016-06-01

Full Text Available Background: The suspension culture of Vigna radiata was selected for biotransformation of hydroquinone to its β-D-glucoside form (arbutin as an important therapeutic and cosmetic compound. Methods: The biotransformation efficiency of a Vigna radiata cell culture in addition to different concentrations of hydroquinone (6-20 mg/100 ml was investigated after 24 hours in comparison to an Echinacea purpurea cell culture and attempts were made to increase the efficacy of the process by adding elicitors. Results: Arbutin was accumulated in cells and found in the media only in insignificant amounts. The arbutin content of the biomass extracts of V. radiata and E. purpurea was different, ranging from 0.78 to 1.89% and 2.00 to 3.55% of dry weight, respectively. V. radiata demonstrated a bioconversion efficiency of 55.82% after adding 8 mg/100 ml precursor, which was comparable with result of 69.53% for E. purpurea cells after adding 10 mg/100 ml hydroquinone (P>0.05. In both cultures, adding hydroquinone in two portions with a 24-hour interval increased the biotransformation efficiency. Different concentrations of methyl jasmonate (25, 50, and 100 µM and chitosan (50 and 100 µg/ml as elicitors increased the bio-efficiency percentage of the V. radiata culture in comparison with the flask containing only hydroquinone. Conclusion: This is the first report of the biotransformation possibility of V. radiata cultures. It was observed the bioconversion capacity increased by adding hydroquinone in two portions, which was comparable to adding an elicitor.

Application of in Vitro Biotransformation Data and ...

Science.gov (United States)

The adverse biological effects of toxic substances are dependent upon the exposure concentration and the duration of exposure. Pharmacokinetic models can quantitatively relate the external concentration of a toxicant in the environment to the internal dose of the toxicant in the target tissues of an exposed organism. The exposure concentration of a toxic substance is usually not the same as the concentration of the active form of the toxicant that reaches the target tissues following absorption, distribution, and biotransformation of the parent toxicant. Biotransformation modulates the biological activity of chemicals through bioactivation and detoxication pathways. Many toxicants require biotransformation to exert their adverse biological effects. Considerable species differences in biotransformation and other pharmacokinetic processes can make extrapolation of toxicity data from laboratory animals to humans problematic. Additionally, interindividual differences in biotransformation among human populations with diverse genetics and lifestyles can lead to considerable variability in the bioactivation of toxic chemicals. Compartmental pharmacokinetic models of animals and humans are needed to understand the quantitative relationships between chemical exposure and target tissue dose as well as animal to human differences and interindividual differences in human populations. The data-based compartmental pharmacokinetic models widely used in clinical pharmacology ha

Biotransformation of soy flour isoflavones by Aspergillus niger NRRL 3122 β-glucosidase enzyme.

Science.gov (United States)

Abdella, Asmaa; El-Baz, Ashraf F; Ibrahim, Ibrahim A; Mahrous, Emad Eldin; Yang, Shang-Tian

2017-12-11

β-glucosidase enzyme produced from Aspergillus niger NRRL 3122 has been partially purified and characterised. Its molecular weight was 180 KDa. The optimal pH and temperature were 3.98 and 55 °C, respectively. It promoted the hydrolysis of soy flour isoflavone glycosides to their aglycone. Two-level Plackett-Burman design was applied and effective variables for genistein production were determined. Reaction time had a significant positive effect, and pH had a significant negative effect. They were further evaluated using Box-Behnken model. Accordingly, the optimal combination of the major reaction affecting factors was reaction time, 5 h and pH, 4. The concentration of genistein increased by 11.73 folds using this optimal combination. The antioxidant activity of the non-biotransformed and biotransformed soy flour extracts was determined by DPPH method. It was found that biotransformation increased the antioxidant activity by four folds.

Isolation and biotransformation of goniothalamin in the production of goniothalamin analogue

Science.gov (United States)

Azizan, Izzatul Hidayah; Khalid, Rozida Mohd; Din, Laily; Latip, Jalifah

2016-11-01

Goniothalamin is a pharmacologically active styrylpyrone compound extracted from Goniothalamus species. It was found to be selectively preventing proliferation of several cancer cell lines without being cytotoxic towards normal cells. Further research on this compound and its derivatives revealed that some of the derivatives also possess anti proliferative activity. The purpose of this study is to synthesise goniothalamin derivatives via biotransformation of goniothalamin using an enzyme assay. Goniothalamin which was isolated from Goniothalamus andersonii, was allowed to react with dienelactone hydrolase for 30 minutes. The enzyme reaction's product was extracted and analysed using LC-MS. Based on the pseudomelecular ion, one goniothalamin analogue with dihydro functionality was obtained.

Biotransformering af pyren i havbørsteormen Nereis virens

DEFF Research Database (Denmark)

Jørgensen, Anne; Giessing, Anders; Juul Rasmussen, Lene

føden og ved overførsel over epithelet. Graden af systemisk akkumulering af PAHer afhænger af optaget men ligeledes af effektiviteten af biotransformering i den pågældende organisme. N. virens er kendt for effektivt at biotransformere PAHer. I nærværende undersøgelse blev biotransformering undersøgt med......-glucuronid er den fase II metabolit der primært produceres ved biotransformering af pyren. Dette indikerer at de vigtigste enzymer i biotransformering af pyren i N. virens er CYP enzymer og glucuronosyl transferase enzymer....

Biotransformation of pesticides in saturated-zone materials

Science.gov (United States)

Hoyle, Blythe L.; Arthur, Ellen L.

Many studies have been conducted to evaluate pesticide contamination of groundwater in the United States, but investigations of pesticide biotransformation in saturated zones are much less numerous than in surface soils. Because results of studies using soils are not directly applicable to the subsurface, the purpose of this paper is to illustrate examples of pesticide biotransformation in saturated-zone materials. Although it must be considered with caution, the US Environmental Protection Agency's (EPA) "Pesticides in Ground Water Database" was used to focus the discussion on the biotransformation potential of dibromoethane (EDB), atrazine, acetanilide herbicides, and aldicarb, all of which have been detected in groundwater in the United States. Results of more than two dozen studies indicate that a biotransformation potential for these pesticides exists in saturated-zone materials, although for any given pesticide substantial differences in biotransformation occurred. These variations were due both to differences in experimental methods and to heterogeneities in the subsurface materials under investigation. However, because biotransformation mechanisms were not well investigated, it is generally not possible to extrapolate predictions of biotransformation potential beyond the specific sites investigated. These results highlight the need to better understand microbial genetic regulation of biotransformation processes so that genetic information may be effectively incorporated into future investigations of biotransformation potential in the subsurface. Résumé De nombreuses études ont été réalisées pour évaluer le degré de pollution des aquifères par les pesticides aux États-Unis, mais les recherches concernant la biotransformation des pesticides dans les eaux souterraines sont beaucoup moins nombreuses que dans les sols. Du fait que les résultats des études concernant les sols ne sont pas directement applicables au milieu souterrain, le propos de cet

Is arsenic biotransformation a detoxification mechanism for microorganisms?

International Nuclear Information System (INIS)

Rahman, M. Azizur; Hassler, Christel

2014-01-01

Arsenic (As) is extremely toxic to living organisms at high concentration. In aquatic systems, As exists in different chemical forms. The two major inorganic As (iAs) species are As V , which is thermodynamically stable in oxic waters, and As III , which is predominant in anoxic conditions. Photosynthetic microorganisms (e.g., phytoplankton and cyanobacteria) take up As V , biotransform it to As III , then biomethylate it to methylarsenic (MetAs) forms. Although As III is more toxic than As V , As III is much more easily excreted from the cells than As V . Therefore, majority of researchers consider the reduction of As V to As III as a detoxification process. The biomethylation process results in the conversion of toxic iAs to the less toxic pentavalent MetAs forms (monomethylarsonate; MMA V , dimethylarsonate; DMA V , and trimethylarsenic oxide; TMAO V ) and trimethylarsine (TMAO III ). However, biomethylation by microorganisms also produces monomethylarsenite (MMA III ) and dimethylarsenite (DMA III ), which are more toxic than iAs, as a result of biomethylation by the microorganisms, demonstrates the need to reconsider to what extent As biomethylation contributes to a detoxification process. In this review, we focused on the discussion of whether the biotransformation of As species in microorganisms is really a detoxification process with recent data

Sex differences in hepatic and intestinal contributions to nevirapine biotransformation in rats.

Science.gov (United States)

Pinheiro, P F; Marinho, A T; Antunes, A M M; Marques, M M; Pereira, S A; Miranda, J P

2015-05-25

The understanding of the intestine contribution to drug biotransformation improved significantly in recent years. However, the sources of inter-individual variability in intestinal drug biotransformation, namely sex-differences, are still elusive. Nevirapine (NVP) is an orally taken anti-HIV drug associated with severe idiosyncratic reactions elicited by toxic metabolites, with women at increased risk. As such, NVP is a good model to assess sex-dimorphic metabolism. The aim of this study was to perform a comparative profiling of NVP biotransformation in rat intestine and liver and evaluate whether or not it is organ- and sex-dependent. Therefore, nevirapine-containing solutions were perfused through the intestine, in a specially designed chamber, or incubated with liver slices, from male and female Wistar rats. The levels of NVP and its Phase I metabolites were quantified by HPLC-UV. Liver incubation experiments yielded the metabolites 2-, 3-, 8-, and 12-OH-NVP, being 12-OH-NVP and 2-OH-NVP the major metabolites in males and females, respectively. Inter-sex differences in the metabolic profile were also detected in the intestine perfusion experiments. Herein, the metabolites 3- and 12-OH-NVP were only found in male rats, whereas 2-OH-NVP levels were higher in females, both in extraluminal (pbiotransformation was observed, strengthening the relevance of the intestinal contribution in the biotransformation of orally taken-drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Biotransformation of chlorpyrifos and endosulfan by bacteria and fungi.

Science.gov (United States)

Supreeth, M; Raju, N S

2017-08-01

Large quantities of pesticides are applied on crops to protect them from pests in modern agricultural practices around the globe. The two insecticides, chlorpyrifos, belonging to the organophosphorous group and endosulfan, belonging to the organochlorine group, are vastly used insecticides on agricultural crops in the last three decades. Hence, both these insecticides are ubiquitous in the environment. Once applied, these two insecticides undergo transformation in the environment either biologically or non-biologically. Microbial degradation has been considered a safe and cost-effective method for removing contaminants from the environment. Both the insecticides have been subjected to biodegradation studies using various bacteria and fungi by the researchers. Here, in this review, we report on biotransformed products formed during the course of biodegradation of these two insecticides and also discuss about the aftereffects of their transformed metabolites. This is important, because the primary biotransformed metabolites 3,5,6, trichloro-2-pyridinol of chlorpyrifos and endosulfan sulfate of endosulfan are toxic as their parent compounds and are noxious to variety of organisms. In conclusion, it is recommended to obtain microbial cultures capable of mineralizing pesticides completely without formation of any such toxic by-product before adopting bioremediation or bioaugmentation technology.

Biotransformation of pharmaceuticals under nitrification, nitratation and heterotrophic conditions

International Nuclear Information System (INIS)

Fernandez-Fontaina, E.; Gomes, I.B.; Aga, D.S.; Omil, F.; Lema, J.M.; Carballa, M.

2016-01-01

The effect of nitrification, nitratation and heterotrophic conditions on the biotransformation of several pharmaceuticals in a highly enriched nitrifying activated sludge was evaluated in this study by selective activation of ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB) and heterotrophic bacteria. Nitrifiers displayed a noticeable capacity to process ibuprofen due to hydroxylation by ammonia monooxygenase (AMO) to produce 2-hydroxy-ibuprofen. Naproxen was also biotransformed under nitrifying conditions. On the other hand, heterotrophic bacteria present in the nitrifying activated sludge (NAS) biotransformed sulfamethoxazole. In contrast, both nitrifying and heterotrophic activities were ineffective against diclofenac, diazepam, carbamazepine and trimethoprim. Similar biotransformation rates of erythromycin, roxithromycin and fluoxetine were observed under all conditions tested. Overall, results from this study give more evidence on the role of the different microbial communities present in activated sludge reactors on the biological removal of pharmaceuticals. - Highlights: • The removal of pharmaceuticals in nitrifying activated sludge (NAS) was studied. • Nitrifying activity increases biotransformation rate of ibuprofen and naproxen. • Hydroxylation of ibuprofen by ammonia monooxygenase of ammonia oxidizing bacteria • Heterotrophic activity enhances biotransformation of sulfamethoxazole in NAS. • Recalcitrance of trimethoprim, diclofenac, carbamazepine and diazepam in NAS

Biotransformation of pharmaceuticals under nitrification, nitratation and heterotrophic conditions

Energy Technology Data Exchange (ETDEWEB)

Fernandez-Fontaina, E., E-mail: eduardo.fernandez.fontaina@usc.es [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Gomes, I.B. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Aga, D.S. [Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States); Omil, F.; Lema, J.M.; Carballa, M. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain)

2016-01-15

The effect of nitrification, nitratation and heterotrophic conditions on the biotransformation of several pharmaceuticals in a highly enriched nitrifying activated sludge was evaluated in this study by selective activation of ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB) and heterotrophic bacteria. Nitrifiers displayed a noticeable capacity to process ibuprofen due to hydroxylation by ammonia monooxygenase (AMO) to produce 2-hydroxy-ibuprofen. Naproxen was also biotransformed under nitrifying conditions. On the other hand, heterotrophic bacteria present in the nitrifying activated sludge (NAS) biotransformed sulfamethoxazole. In contrast, both nitrifying and heterotrophic activities were ineffective against diclofenac, diazepam, carbamazepine and trimethoprim. Similar biotransformation rates of erythromycin, roxithromycin and fluoxetine were observed under all conditions tested. Overall, results from this study give more evidence on the role of the different microbial communities present in activated sludge reactors on the biological removal of pharmaceuticals. - Highlights: • The removal of pharmaceuticals in nitrifying activated sludge (NAS) was studied. • Nitrifying activity increases biotransformation rate of ibuprofen and naproxen. • Hydroxylation of ibuprofen by ammonia monooxygenase of ammonia oxidizing bacteria • Heterotrophic activity enhances biotransformation of sulfamethoxazole in NAS. • Recalcitrance of trimethoprim, diclofenac, carbamazepine and diazepam in NAS.

Allometric scaling of hepatic biotransformation in rainbow trout

Science.gov (United States)

Biotransformation can markedly reduce the extent to which hydrophobic organic chemicals accumulate in fish. However, predicting the impacts of biotransformation on chemical accumulation is complicated by a number of factors, including the possible influence of differences in fis...

Is arsenic biotransformation a detoxification mechanism for microorganisms?

Energy Technology Data Exchange (ETDEWEB)

Rahman, M. Azizur, E-mail: Mohammad.Rahman@uts.edu.au [Centre for Environmental Sustainability, School of the Environment, Faculty of Science, University of Technology, P.O. Box 123, Broadway, Sydney, NSW 2007 (Australia); Hassler, Christel [Marine and Lake Biogeochemistry, Institute F. A. Forel, University of Geneva, 10 rte de Suisse, Versoix, 1290 Switzerland (Switzerland)

2014-01-15

Arsenic (As) is extremely toxic to living organisms at high concentration. In aquatic systems, As exists in different chemical forms. The two major inorganic As (iAs) species are As{sup V}, which is thermodynamically stable in oxic waters, and As{sup III}, which is predominant in anoxic conditions. Photosynthetic microorganisms (e.g., phytoplankton and cyanobacteria) take up As{sup V}, biotransform it to As{sup III}, then biomethylate it to methylarsenic (MetAs) forms. Although As{sup III} is more toxic than As{sup V}, As{sup III} is much more easily excreted from the cells than As{sup V}. Therefore, majority of researchers consider the reduction of As{sup V} to As{sup III} as a detoxification process. The biomethylation process results in the conversion of toxic iAs to the less toxic pentavalent MetAs forms (monomethylarsonate; MMA{sup V}, dimethylarsonate; DMA{sup V}, and trimethylarsenic oxide; TMAO{sup V}) and trimethylarsine (TMAO{sup III}). However, biomethylation by microorganisms also produces monomethylarsenite (MMA{sup III}) and dimethylarsenite (DMA{sup III}), which are more toxic than iAs, as a result of biomethylation by the microorganisms, demonstrates the need to reconsider to what extent As biomethylation contributes to a detoxification process. In this review, we focused on the discussion of whether the biotransformation of As species in microorganisms is really a detoxification process with recent data.

Process for Biotransformation of Androsta-4-ene-3, 17-Dione (4-AD) to Androsta-1,4-Diene-3,17-Dione (ADD).

Science.gov (United States)

Prakash, Surya; Bajaj, Abhay

2017-01-01

Androsta-1,4-diene-3,17-dione (androstadienedione, ADD) is key intermediate for the organic synthesis of a variety of female sex hormones such as estrone, estradiol, estriol and other related derivatives. De novo synthesis of this molecule is not yet reported in any form of living system, i.e., microbial, plant, and animal. The structural complexities due to presence of several chiral carbon centers create significant hurdles in chemical synthesis of such molecules. Microbe-mediated biotransformation offer a highly reliable, cost-effective, and relatively non hazardous way for commercial manufacturing of steroidal key intermediates. Currently microbial biotransformations are extensively being exploited for large-scale production of basic intermediates such as androstenedione (AD), ADD, and several types of hydroxylated derivatives of androstane compounds. In this chapter several aspects of microbial biotransformation process of AD to ADD are discussed.

Bioavailability of dietary phenolic compounds: Review

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Erick Gutiérrez-Grijalva Paul Gutiérrez-Grijalva

2015-12-01

Full Text Available Phenolic compounds are ubiquitous in plant-based foods. High dietary intake of fruits, vegetables and cereals is related to a decreased rate in chronic diseases. Phenolic compounds are thought to be responsible, at least in part, for those health effects. Nonetheless, phenolic compounds bioaccessibility and biotransformation is often not considered in these studies; thus, a precise mechanism of action of phenolic compounds is not known. In this review we aim to present a comprehensive knowledge of the metabolic processes through which phenolic compounds go after intake.

Elucidation of biotransformation of diclofenac and 4′hydroxydiclofenac during biological wastewater treatment

International Nuclear Information System (INIS)

Bouju, Helene; Nastold, Peter; Beck, Birgit; Hollender, Juliane; Corvini, Philippe F.-X.; Wintgens, Thomas

2016-01-01

Highlights: • The presence of DF specific degraders in activated sludge was confirmed. • The hydroxylation of DF to 4′OHDF is a bottleneck in diclofenac biodegradation. • Two biotransformation end products of DF and 4'OHDF were identified. • In wastewater treatment plants 4′-OHDF can be of both human and microbial origin. • A tentative biotransformation pathway for DF and 4′OHDF was proposed. - Abstract: This study aimed at gaining knowledge on the degradation pathway during biological treatment of wastewater of diclofenac and 4′-hydroxydiclofenac, its main human metabolite. For that purpose, an aerobic MBR was acclimatised to diclofenac, and the MBR biomass subsequently incubated with "1"4C-diclofenac or "1"4C-4′hydroxydiclofenac over 25 days. It was demonstrated that diclofenac degradation was much slower and limited than that of 4′-hydroxydiclofenac. Indeed, after 18 days of batch incubation, diclofenac was removed up to 40%, this rate remained stable till the end of the experiment, while 4′-hydroxydiclofenac was completely degraded within nine days. The analyses of supernatant samples have shown that diclofenac degradation led to four transformation products, more polar than the parent compound, one of them being 4′-hydroxydiclofenac. The degradation of 4′-hydroxydiclofenac led to the formation of the same metabolites than those detected during diclofenac degradation. With these results, the hydroxylation of diclofenac to 4′-hydroxydiclofenac was identified as one major bottleneck in diclofenac degradation during biological treatment of wastewater.

Elucidation of biotransformation of diclofenac and 4′hydroxydiclofenac during biological wastewater treatment

Energy Technology Data Exchange (ETDEWEB)

Bouju, Helene; Nastold, Peter [Institute for Ecopreneurship, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Gründenstrasse 40, CH 4132 Muttenz (Switzerland); Beck, Birgit; Hollender, Juliane [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf (Switzerland); Corvini, Philippe F.-X. [Institute for Ecopreneurship, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Gründenstrasse 40, CH 4132 Muttenz (Switzerland); School of the Environment, Nanjing University, Nanjing 210093 (China); Wintgens, Thomas, E-mail: thomas.wintgens@fhnw.ch [Institute for Ecopreneurship, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Gründenstrasse 40, CH 4132 Muttenz (Switzerland)

2016-01-15

Highlights: • The presence of DF specific degraders in activated sludge was confirmed. • The hydroxylation of DF to 4′OHDF is a bottleneck in diclofenac biodegradation. • Two biotransformation end products of DF and 4'OHDF were identified. • In wastewater treatment plants 4′-OHDF can be of both human and microbial origin. • A tentative biotransformation pathway for DF and 4′OHDF was proposed. - Abstract: This study aimed at gaining knowledge on the degradation pathway during biological treatment of wastewater of diclofenac and 4′-hydroxydiclofenac, its main human metabolite. For that purpose, an aerobic MBR was acclimatised to diclofenac, and the MBR biomass subsequently incubated with {sup 14}C-diclofenac or {sup 14}C-4′hydroxydiclofenac over 25 days. It was demonstrated that diclofenac degradation was much slower and limited than that of 4′-hydroxydiclofenac. Indeed, after 18 days of batch incubation, diclofenac was removed up to 40%, this rate remained stable till the end of the experiment, while 4′-hydroxydiclofenac was completely degraded within nine days. The analyses of supernatant samples have shown that diclofenac degradation led to four transformation products, more polar than the parent compound, one of them being 4′-hydroxydiclofenac. The degradation of 4′-hydroxydiclofenac led to the formation of the same metabolites than those detected during diclofenac degradation. With these results, the hydroxylation of diclofenac to 4′-hydroxydiclofenac was identified as one major bottleneck in diclofenac degradation during biological treatment of wastewater.

BIOTRANSFORMATION OF FERULIC ACID BY THE PHYTOPATHOGENIC FUNGI Colletotrichum acutatum AND Lasiodiplodia theobromae

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Manuel Alejandro Numpaque

2016-01-01

Full Text Available The microbial transformation of ferulic acid (FA offers a cleaner, more economical alternative for the natural production of flavorings and fragrances. In the present study, the biotransformation of FA using the filamentous phytopathogenic fungi Colletotrichum acutatum and Lasiodiplodia theobromae was researched. Initially, the toxicity of FA against both fungi was evaluated; the FA displayed a moderate toxicity (total inhibition at concentrations ≥ 2000 mg L-1 and apparently a detoxification mechanism was present. Afterwards, the microorganisms were incubated with the substrate at room conditions using a Czapek-Dox culture medium. The results demonstrated that the FA was mainly converted to 4-vinylguaiacol, reaching the highest abundance within the first 48 hours. To a lesser extent, acetovanillone, ethylguaiacol, and vanillin, among others, were produced. Interestingly, the compounds generated in the biotransformation of FA with C. acutatum and L. theobromae have been used as flavorings. Based on the identified metabolites, a possible metabolic pathway was proposed.

Biotransformation of Lactones with Methylcyclohexane Ring and Their Biological Activity

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Katarzyna Wińska

2016-12-01

Full Text Available The aim of the study was to obtain biological active compounds during biotransformation. Three bicyclic halolactones with methylcyclohexane ring (2-chloro-4-methyl-9-oxabicyclo-[4.3.0]nonan-8-one, 2-bromo-4-methyl-9-oxabicyclo[4.3.0]nona- -8-one and 2-iodo-4-methyl-9-oxabicyclo[4.3.0]nonan-8-one obtained from the corresponding γ,δ-unsaturated acid were subjected to a screening biotransformation using 22 fungal strains. Two of these strains (Cunninghamella japonica AM472 and Fusarium culmorum AM10 were able to transform halolactones into 2-hydroxy-4-methyl-9-oxabicyclo[4.3.0]nonan-8-one by hydrolytic dehalogenation with good yield. The biotransformation product was structurally different from its synthetically prepared analog. All halolactones and hydroxylactones were tested for their biological activity. The chlorolactone inhibited growth of Staphylococcus aureus (max ΔOD = 0, Escherichia coli (max ΔOD = 0.3 and Candida albicans (max ΔOD = 0 strains. Bromolactone caused inhibition of growth of Staphylococcus aureus (max ΔOD = 0 and Fusarium linii (max ΔOD = 0 strains. Iodolactone limited growth of Staphylococcus aureus (max ΔOD = 0, Escherichia coli (max ΔOD = 0.25, Candida albicans (max ΔOD = 0.45 and Pseudomonas fluorescens (max ΔOD = 0.42 strains. Hydroxylactone caused inhibition of growth of Staphylococcus aureus (max ΔOD = 0.36 and Pseudomonas fluorescens (max ΔOD = 0.39 strains only. The test performed on aphids Myzus persicae (Sulz. showed that chloro- and bromolactone exhibited deterrent activity after 24 h (ID = 0.5 and 0.4, respectively, while hydroxylactone was a weak attractant (ID = −0.3.

Microbial-Catalyzed Biotransformation of Multifunctional Triterpenoids Derived from Phytonutrients

Science.gov (United States)

Shah, Syed Adnan Ali; Tan, Huey Ling; Sultan, Sadia; Mohd Faridz, Muhammad Afifi Bin; Mohd Shah, Mohamad Azlan Bin; Nurfazilah, Sharifah; Hussain, Munawar

2014-01-01

Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids. They offer efficient and economical ways to produce semi-synthetic analogues and novel lead molecules. Microorganisms such as bacteria and fungi could catalyze chemo-, regio- and stereospecific hydroxylations of diverse triterpenoid substrates that are extremely difficult to produce by chemical routes. During recent years, considerable research has been performed on the microbial transformation of bioactive triterpenoids, in order to obtain biologically active molecules with diverse structures features. This article reviews the microbial modifications of tetranortriterpenoids, tetracyclic triterpenoids and pentacyclic triterpenoids. PMID:25003642

Biotransformation of catechin and extraction of active polysaccharide from green tea leaves via simultaneous treatment with tannase and pectinase.

Science.gov (United States)

Baik, Joo Hyun; Shin, Kwang-Soon; Park, Yooheon; Yu, Kwang-Won; Suh, Hyung Joo; Choi, Hyeon-Son

2015-08-30

Green tea is a dietary source of bioactive compounds for human health. Enzymatic treatments induce the bioconversion of bioactive components, which can improve biological activities. In this study, we investigated the effect of simultaneous treatment with tannase and Rapidase on biotransformation of catechins and extraction of polysaccharide from green tea extract (GTE). Tannase and pectinase treatments induced the biotransformation of catechins and altered tea polysaccharide () content. The addition of GTE to the enzyme reaction resulted in a significant increase in degallated catechins, including gallic acid, a product of the tannase reaction (314.5-4076.0 µg mL(-1)) and a reduction in epigallocatechin gallate (EGCG). Biotransformation of catechins improved the radical scavenging activity of GTE. Pectinase treatment led to change of TPS composition in GTE by hydrolyzing polysaccharides. In addition, pectinase-driven hydrolysis in polysaccharides significantly increased TPS-induced Interleukin 6 (IL-6) production in macrophages. In particular, treatment of Rapidase (TPS-Ra) led to the highest IL-6 production among TPS samples, similar to treatment of highly purified pectinase (TPS-GTE), a positive control. Simultaneous processing with tannase and Rapidase can be an efficient method for the extraction of bioactive polysaccharides and biotransformation of catechins with enhanced radical scavenging activity from green tea. © 2014 Society of Chemical Industry.

Proteomic Insights on the Metabolism of Penicillium janczewskii during the Biotransformation of the Plant Terpenoid Labdanolic Acid

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Isabel Martins

2017-07-01

Full Text Available Plant terpenoids compose a natural source of chemodiversity of exceptional value. Many of these compounds own biological/pharmacological activity, others are regarded as unique chemical skeletons for the synthesis of derivatives with improved properties. Functional chemical modification of terpenoids through biotransformation frequently relies on the use of Ascomycota strains, but information on major cellular responses is still largely lacking. Penicillium janczewskii mediates a stereo-selective hydroxylation of labdanolic acid (LA—terpenoid found abundantly in Cistus ladanifer—producing 3β-hydroxy-labdanolic acid with yields >90%. Herein, combined analyses of mycelial and extracellular differential proteomes demonstrated that the plant terpenoid increased stress responses, especially against oxidative stress (e.g., accumulation of superoxide dismutase and apparently altered mitochondria functioning. One putative cytochrome P450 monooxygenase differentially accumulated in the secretome and the terpenoid bioconversion was inhibited in vivo in the presence of a P450 inhibitor. The stereo-selective hydroxylation of the plant terpenoid is likely mediated by P450 enzymes, yet its unequivocal identity remains unclear. To the best of our knowledge, this is the first time that proteomics was used to investigate how a plant terpenoid impacts the metabolism of a filamentous fungus during its efficiently biotransformation. Our findings may encourage the development of new strategies for the valorization of plant natural resources through biotechnology.

IN VITRO CYTOTOXICITY OF AROMATIC AEROBIC BIOTRANSFORMATION PRODUCTS IN BLUEGILL SUNFISH BF-2 CELLS

Science.gov (United States)

Toluene (methylbenzene) is a common environmental pollutant that is found in many hazardous waste sites and it is an aquifer contaminant. A concern is the potential risk to human and ecosystem health due to exposure to toluene and its major biotransformation products. The cytotox...

Biotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd)

Energy Technology Data Exchange (ETDEWEB)

Schmidt, Tobias [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany); Bertermann, Rüdiger [Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg (Germany); Rusch, George M.; Tveit, Ann [Honeywell, P.O. Box 1057, Morristown, NJ 07962-1057 (United States); Dekant, Wolfgang, E-mail: dekant@toxi.uni-wuerzburg.de [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany)

2013-05-01

trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is negative in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected for 48 h after the end of the exposure. Study specimens were analyzed for metabolites using {sup 19}F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t{sub 1/2} < 6 h) and the extent of biotransformation of trans-HCFO-1233zd was determined as approximately 0.01% of received dose in rabbits and approximately 0.002% in rats. trans-HCFO-1233zd undergoes both oxidative biotransformation and glutathione conjugation at very low rates. The low extent of biotransformation and the rapid excretion of metabolites formed are consistent with the very low potential for toxicity of trans-HCFO-1233zd in mammals. - Highlights: ► No lethality and clinical signs were observed. ► Glutathione S-transferase and cytochrome P-450 dependent

A Macrosphelide as the Unexpected Product of a Pleurotus ostreatus Strain-Mediated Biotransformation of Halolactones Containing the gem-Dimethylcyclohexane Ring. Part 1

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Katarzyna Wińska

2016-06-01

Full Text Available The aim of the study was to obtain new compounds during biotransformation of two halocompounds, the δ-bromo and δ-iodo-γ-bicyclolactones 1 and 2. Unexpectedly Pleurotus ostreatus produced together with the hydroxylactone, 2-hydroxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonane-8-one (3, its own metabolite (3S,9S,15S-(6E,12E-3,9,15-trimethyl-4,10,16-trioxacyclohexa-deca-6,12-diene-1,5,8,11,14-pentaone (4. The method presented here, in which this macrosphelide 4 was obtained by biotransformation, has not been previously described in the literature. To the best of our knowledge, this compound has been prepared only by chemical synthesis to date. This is the first report on the possibility of the biosynthesis of this compound by the Pleurotus ostreatus strain. The conditions and factors, like temperature, salts, organic solvents, affecting the production of this macrosphelide by Pleurotus ostreatus strain were examined. The highest yield of macroshphelide production was noticed for halolactones, as well with iodide, bromide, iron and copper (2+ ions as inductors.

Evaluation of Diuron Tolerance and Biotransformation by Fungi from a Sugar Cane Plantation Sandy-Loam Soil.

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Perissini-Lopes, Bruna; Egea, Tássia Chiachio; Monteiro, Diego Alves; Vici, Ana Cláudia; Da Silva, Danilo Grünig Humberto; Lisboa, Daniela Correa de Oliveira; de Almeida, Eduardo Alves; Parsons, John Robert; Da Silva, Roberto; Gomes, Eleni

2016-12-14

Microorganisms capable of degrading herbicides are essential to minimize the amount of chemical compounds that may leach into other environments. This work aimed to study the potential of sandy-loam soil fungi to tolerate the herbicide Herburon (50% diuron) and to degrade the active ingredient diuron. Verticillium sp. F04, Trichoderma virens F28, and Cunninghamella elegans B06 showed the highest growth in the presence of the herbicide. The evaluation of biotransformation showed that Aspergillus brasiliensis G08, Aspergillus sp. G25, and Cunninghamella elegans B06 had the greatest potential to degrade diuron. Statistical analysis demonstrated that glucose positively influences the potential of the microorganism to degrade diuron, indicating a cometabolic process. Due to metabolites founded by diuron biotransformation, it is indicated that the fungi are relevant in reducing the herbicide concentration in runoff, minimizing the environmental impact on surrounding ecosystems.

Biotransformation of polycyclic aromatic hydrocarbons in marine polychaetes

DEFF Research Database (Denmark)

Jørgensen, Anne; Giessing, Anders; Rasmussen, Lene Juel

2008-01-01

Deposit-feeding polychaetes constitute the dominant macrofauna in marine environments that tend to be depositional centers for organic matter and contaminants. Polychaetes are known to accumulate polycyclic aromatic hydrocarbons (PAHs) from both particulate and dissolved phases but less is known...... about the mechanisms underlying elimination of accumulated PAHs. An important pathway of elimination is through biotransformation which results in increased aqueous solubility of the otherwise hydrophobic PAHs. Biotransformation in marine polychaetes proceeds in a two phased process similar to those...... well studied in vertebrates, phase I enzymes belonging to the Cytochrome P450 (CYP) enzyme family, along with a few phase II enzymes have been identified in marine polychaetes. In this review we aim at highlighting advances in the mechanistic understanding of PAH biotransformation in marine polychaetes...

Microbial biotransformation of bioactive flavonoids.

Science.gov (United States)

Cao, Hui; Chen, Xiaoqing; Jassbi, Amir Reza; Xiao, Jianbo

2015-01-01

The bioactive flavonoids are considered as the most important phytochemicals in food, which exert a wide range of biological benefits for human being. Microbial biotransformation strategies for production of flavonoids have attracted considerable interest because they allow yielding novel flavonoids, which do not exist in nature. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoids by various microbes. The main reactions during microbial biotransformation are hydroxylation, dehydroxylation, O-methylation, O-demethylation, glycosylation, deglycosylation, dehydrogenation, hydrogenation, C ring cleavage of the benzo-γ-pyrone system, cyclization, and carbonyl reduction. Cunninghamella, Penicillium, and Aspergillus strains are very popular to biotransform flavonoids and they can perform almost all the reactions with excellent yields. Aspergillus niger is one of the most applied microorganisms in the flavonoids' biotransformation; for example, A. niger can transfer flavanone to flavan-4-ol, 2'-hydroxydihydrochalcone, flavone, 3-hydroxyflavone, 6-hydroxyflavanone, and 4'-hydroxyflavanone. The hydroxylation of flavones by microbes usually happens on the ortho position of hydroxyl group on the A ring and C-4' position of the B ring and microbes commonly hydroxylate flavonols at the C-8 position. The microorganisms tend to hydroxylate flavanones at the C-5, 6, and 4' positions; however, for prenylated flavanones, dihydroxylation often takes place on the C4α=C5α double bond on the prenyl group (the side chain of A ring). Isoflavones are usually hydroxylated at the C-3' position of the B ring by microorganisms. The microbes convert flavonoids to their 7-O-glycosides and 3-O-glycosides (when flavonoids have a hydroxyl moiety at the C-3 position). The demethylation of multimethoxyl flavonoids by microbes tends to happen at the C-3' and C-4' positions of the B ring. Multimethoxyl flavanones and isoflavone are demethylated at

[Synthesis, biotransformation and pharmacodynamics of a new theophylline derivative].

Science.gov (United States)

Oelschläger, H; Harsche, C; Engel, J

1991-09-01

7-[(RS)2-((S)-1-Methyl-2-phenyl-ethylamino)propyl]-theophylline (3) was not described until now. This fenetylline analogue is available by reaction of 7 with an excess of 2 at 150 degrees C. If 2 reacts with 4, an E2-elimination overwhelms SN-nucleophilic displacement yielding compound 5. In vivo studies with male White-Wistar rats, comparing biotransformation of 3 and 1, demonstrate, that the amount of 2 is decreased from 4.7% of (RS)-2 to 1%, probably due to steric hindrance of the attacking monooxygenases by the methyl group at C-11 of 3. Pharmacodynamic studies of 3, tested with mice, gave similar results to those obtained with 1.

MICROBIAL DEGRADATION OF NITROGEN, OXYGEN AND SULFUR HETEROCYCLIC COMPOUNDS UNDER ANAEROBIC CONDITIONS: STUDIES WITH AQUIFER SAMPLES

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The potential for anaerobic biodegradation of 12 heterocyclic model compounds was studied. Nine of the model compounds were biotransformed in aquifer slurries under sulfate-reducing or methanogenic conditions. The nitrogen and oxygen heterocyclic compounds were more susceptible t...

Biotransformation and metabolic profile of Xian-Ling-Gu-Bao capsule, a traditional Chinese medicine prescription, with rat intestinal microflora by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis.

Science.gov (United States)

Gao, Meng-Xue; Tang, Xi-Yang; Zhang, Feng-Xiang; Yao, Zhi-Hong; Yao, Xin-Sheng; Dai, Yi

2018-04-01

Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine prescription, has been used for the prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence-based medicine. XLGB is usually administered orally, after which its multiple components are brought into contact with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, 12 representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, the metabolic profile of XLGB in rat intestinal microflora was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. As a result, a total of 87 biotransformation components were identified from incubated solutions of 12 representative compounds and XLGB, which underwent 16 metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH 3 ). This demonstrated that the deglycosylation reaction by cleavage of the sugar moieties is the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of 12 representative compounds, a different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was first discovered

pH-dependent biotransformation of ionizable organic micropollutants in activated sludge.

Science.gov (United States)

Gulde, Rebekka; Helbling, Damian E; Scheidegger, Andreas; Fenner, Kathrin

2014-12-02

Removal of micropollutants (MPs) during activated sludge treatment can mainly be attributed to biotransformation and sorption to sludge flocs, whereby the latter process is known to be of minor importance for polar organic micropollutants. In this work, we investigated the influence of pH on the biotransformation of MPs with cationic-neutral speciation in an activated sludge microbial community. We performed batch biotransformation, sorption control, and abiotic control experiments for 15 MPs with cationic-neutral speciation, one control MP with neutral-anionic speciation, and two neutral MPs at pHs 6, 7, and 8. Biotransformation rate constants corrected for sorption and abiotic processes were estimated from measured concentration time series with Bayesian inference. We found that biotransformation is pH-dependent and correlates qualitatively with the neutral fraction of the ionizable MPs. However, a simple speciation model based on the assumption that only the neutral species is efficiently taken up and biotransformed by the cells tends to overpredict the effect of speciation. Therefore, additional mechanisms such as uptake of the ionic species and other more complex attenutation mechanisms are discussed. Finally, we observed that the sorption coefficients derived from our control experiments were small and showed no notable pH-dependence. From this we conclude that pH-dependent removal of polar, ionizable organic MPs in activated sludge systems is less likely an effect of pH-dependent sorption but rather of pH-dependent biotransformation. The latter has the potential to cause marked differences in the removal of polar, ionizable MPs at different operational pHs during activated sludge treatment.

Comparison of biotransformation and efficacy of aminoacetonitrile anthelmintics in vitro.

Science.gov (United States)

Stuchlíková, Lucie; Lecová, Lenka; Jirásko, Robert; Lamka, Jiří; Vokřál, Ivan; Szotáková, Barbora; Holčapek, Michal; Skálová, Lenka

2016-02-01

The present in vitro study was designed to test and compare anthelmintic activity, hepatotoxicity, and biotransformation of four selected aminoacetonitrile derivatives (AADs): monepantel (MOP, anthelmintic approved for the treatment), AAD-970, AAD-1154, and AAD-1336. Micro-agar larval development test, MTT test of cytotoxicity, and biotransformation study coupled with Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique were used for this purpose. Larvae of two Haemonchus contortus strains (drug susceptible and multi-drug resistant) and primary cultures of rat and ovine hepatocytes served as model systems. All AADs (including MOP) exhibited significant larvicidal effect in H. contortus susceptible as well as multi-resistant strains, much higher than those of reference anthelmintics thiabendazole and flubendazole. AAD-1154 provides the best results for most tested parameters among all AADs in this study. The cytotoxicity test showed that all AADs can be considered as nontoxic for hepatocytes. In the biotransformation study, Phase I and Phase II metabolites of AADs were identified and schemes of possible metabolic pathways in ovine hepatocytes were proposed. Biotransformation of MOP was much more extensive than biotransformation of other AADs. Based on obtained results, AAD-1154 and AAD-1336 can be considered as promising candidates for further in vivo testing. Copyright © 2015 John Wiley & Sons, Ltd.

Novel biotransformation and physiological properties of norursodeoxycholic acid in humans

NARCIS (Netherlands)

Hofmann, AF; Zakko, SF; Lira, M; Clerici, C; Hagey, LR; Lambert, KK; Steinbach, JH; Schteingart, CD; Olinga, P; Groothuis, GMM

2005-01-01

Experiments were performed in 2 volunteers to define the biotransformation and physiological properties of norursodeoxycholic acid (norUDCA), the C(23) (C(24)-nor) homolog of UDCA. To complement the in vivo studies, the biotransformation of norUDCA ex vivo using precision-cut human liver slices was

Biotransformation of polychlorinated biphenyls (PCBs) and bioformation of hydroxylated PCBs in fish

Energy Technology Data Exchange (ETDEWEB)

Buckman, Andrea H. [Department of Environmental Biology, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); National Waters Research Institute, Environment Canada, Burlington, Ont., Canada L7R 4A6 (Canada); Wong, Charles S. [Department of Chemistry, University of Alberta, Edmonton, Alta. (Canada); Chow, Elaine A. [Department of Chemistry, University of Alberta, Edmonton, Alta. (Canada); Brown, Scott B. [National Waters Research Institute, Environment Canada, Burlington, Ont., L7R 4A6 (Canada); Solomon, Keith R. [Department of Environmental Biology, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Fisk, Aaron T. [Warnell School of Forest Resources, University of Georgia, Athens, GA 30602-2152 (United States)]. E-mail: afisk@smokey.forestry.uga.edu

2006-06-15

Hydroxylated PCBs (OH-PCBs) are a class of organic contaminants that have been found recently in the plasma of Great Lakes fish, the source of which is either bioformation from PCBs or accumulation from the environment. To address the potential for fish to biotransform PCBs and bioform OH-PCBs juvenile rainbow trout (Oncorhynchus mykiss; {approx}80 g) were exposed to dietary concentrations of an environmentally relevant mixture of PCBs. Eight OH-PCBs were found in the plasma of rainbow trout after 30 days of exposure to the PCBs, the relative pattern of which was similar to those observed in wild lake trout (Salvelinus namaycush) from Lake Ontario. Hydroxylated-PCBs were not found (detection limit 0.02 pg/g) in the food or control (not PCB-exposed) fish. A curvilinear log t {sub 1/2}-log K {sub ow} relationship for recalcitrant PCBs was found, similar to previously reported relationships, although t {sub 1/2} values were longer and shorter than studies using smaller fish or cooler temperatures, respectively. A number of PCB congeners fell below the log t {sub 1/2}-log K {sub ow} relationship providing the first estimates of non-chiral PCB biotransformation rates in fish. Enantioselective degradation of the chiral congeners PCBs 91 and 136, also indicated biotransformation. Biotransformation of PCBs was structure-dependent with greater biotransformation of PCBs with vicinal hydrogen atoms in the meta/para positions, suggesting CYP 2B-like biotransformation. Other chiral congeners with a meta/para substitution pattern showed no enantioselective degradation but were biotransformed based on the log t {sub 1/2}-log K {sub ow} relationship. The results of this study demonstrate that laboratory held rainbow trout can biotransform a number of PCB congeners and that bioformation is likely an important source of OH-PCBs in wild salmonids of the Great Lakes.

Biotransformation of polychlorinated biphenyls (PCBs) and bioformation of hydroxylated PCBs in fish

International Nuclear Information System (INIS)

Buckman, Andrea H.; Wong, Charles S.; Chow, Elaine A.; Brown, Scott B.; Solomon, Keith R.; Fisk, Aaron T.

2006-01-01

Hydroxylated PCBs (OH-PCBs) are a class of organic contaminants that have been found recently in the plasma of Great Lakes fish, the source of which is either bioformation from PCBs or accumulation from the environment. To address the potential for fish to biotransform PCBs and bioform OH-PCBs juvenile rainbow trout (Oncorhynchus mykiss; ∼80 g) were exposed to dietary concentrations of an environmentally relevant mixture of PCBs. Eight OH-PCBs were found in the plasma of rainbow trout after 30 days of exposure to the PCBs, the relative pattern of which was similar to those observed in wild lake trout (Salvelinus namaycush) from Lake Ontario. Hydroxylated-PCBs were not found (detection limit 0.02 pg/g) in the food or control (not PCB-exposed) fish. A curvilinear log t 1/2 -log K ow relationship for recalcitrant PCBs was found, similar to previously reported relationships, although t 1/2 values were longer and shorter than studies using smaller fish or cooler temperatures, respectively. A number of PCB congeners fell below the log t 1/2 -log K ow relationship providing the first estimates of non-chiral PCB biotransformation rates in fish. Enantioselective degradation of the chiral congeners PCBs 91 and 136, also indicated biotransformation. Biotransformation of PCBs was structure-dependent with greater biotransformation of PCBs with vicinal hydrogen atoms in the meta/para positions, suggesting CYP 2B-like biotransformation. Other chiral congeners with a meta/para substitution pattern showed no enantioselective degradation but were biotransformed based on the log t 1/2 -log K ow relationship. The results of this study demonstrate that laboratory held rainbow trout can biotransform a number of PCB congeners and that bioformation is likely an important source of OH-PCBs in wild salmonids of the Great Lakes

Xylitol production from waste xylose mother liquor containing miscellaneous sugars and inhibitors: one-pot biotransformation by Candida tropicalis and recombinant Bacillus subtilis.

Science.gov (United States)

Wang, Hengwei; Li, Lijuan; Zhang, Lebin; An, Jin; Cheng, Hairong; Deng, Zixin

2016-05-16

efficient under optimized conditions. Moreover, our study of one-pot biotransformation also provides useful information on the combination of biotechnological processes for the biotransformation of other compounds.

Biotransformation of ferulic acid to 4-vinyl guaiacol by Lactobacillus ...

African Journals Online (AJOL)

Continuously growing demand for natural flavors has led to a tremendous increase in biotransformation process employing microorganisms of different genera using ferulic acid (FA) as the precursor. In this study, potential of Lactobacillus farciminis (ATCC 29644) for biotransformation of FA to 4-vinyl guaiacol (4VG) was ...

Arsenic in the human food chain, biotransformation and toxicology--Review focusing on seafood arsenic.

Science.gov (United States)

Molin, Marianne; Ulven, Stine Marie; Meltzer, Helle Margrete; Alexander, Jan

2015-01-01

Fish and seafood are main contributors of arsenic (As) in the diet. The dominating arsenical is the organoarsenical arsenobetaine (AB), found particularly in finfish. Algae, blue mussels and other filter feeders contain less AB, but more arsenosugars and relatively more inorganic arsenic (iAs), whereas fatty fish contain more arsenolipids. Other compounds present in smaller amounts in seafood include trimethylarsine oxide (TMAO), trimethylarsoniopropionate (TMAP), dimethylarsenate (DMA), methylarsenate (MA) and sulfur-containing arsenicals. The toxic and carcinogenic arsenical iAs is biotransformed in humans and excreted in urine as the carcinogens dimethylarsinate (DMA) and methylarsonate (MA), producing reactive intermediates in the process. Less is known about the biotransformation of organoarsenicals, but new insight indicates that bioconversion of arsenosugars and arsenolipids in seafood results in urinary excretion of DMA, possibly also producing reactive trivalent arsenic intermediates. Recent findings also indicate that the pre-systematic metabolism by colon microbiota play an important role for human metabolism of arsenicals. Processing of seafood may also result in transformation of arsenicals. Copyright © 2015 Elsevier GmbH. All rights reserved.

Complementation of biotransformations with chemical C-H oxidation: copper-catalyzed oxidation of tertiary amines in complex pharmaceuticals.

Science.gov (United States)

Genovino, Julien; Lütz, Stephan; Sames, Dalibor; Touré, B Barry

2013-08-21

The isolation, quantitation, and characterization of drug metabolites in biological fluids remain challenging. Rapid access to oxidized drugs could facilitate metabolite identification and enable early pharmacology and toxicity studies. Herein, we compared biotransformations to classical and new chemical C-H oxidation methods using oxcarbazepine, naproxen, and an early compound hit (phthalazine 1). These studies illustrated the low preparative efficacy of biotransformations and the inability of chemical methods to oxidize complex pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a broad range of functionalities and displays a high level of chemoselectivity, which is not generally explained by the strength of the C-H bonds but by the individual structural chemotype. This study represents a first step toward establishing a chemical toolkit (chemotransformations) that can selectively oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug metabolites.

Isolated and mixed effects of diuron and its metabolites on biotransformation enzymes and oxidative stress response of Nile tilapia (Oreochromis niloticus).

Science.gov (United States)

Felício, Andréia Arantes; Freitas, Juliane Silberschmidt; Scarin, Jéssica Bolpeti; de Souza Ondei, Luciana; Teresa, Fabrício Barreto; Schlenk, Daniel; de Almeida, Eduardo Alves

2018-03-01

Diuron is one of the most used herbicide in the world, and its field application has been particularly increased in Brazil due to the expansion of sugarcane crops. Diuron has often been detected in freshwater ecosystems and it can be biodegraded into three main metabolites in the environment, the 3,4-dichloroaniline (DCA), 3,4-dichlorophenylurea (DCPU) and 3,4-dichlorophenyl-N-methylurea (DCPMU). Negative effects under aquatic biota are still not well established for diuron, especially when considering its presence in mixture with its different metabolites. In this study, we evaluated the effects of diuron alone or in combination with its metabolites, DCPMU, DCPU and 3,4-DCA on biochemical stress responses and biotransformation activity of the fish Oreochromis niloticus. Results showed that diuron and its metabolites caused significant but dispersed alterations in oxidative stress markers and biotransformation enzymes, except for ethoxyresorufin-O-deethylase (EROD) activity, that presented a dose-dependent increase after exposure to either diuron or its metabolites. Glutathione S-transferase (GST) activity was significant lower in gills after exposure to diuron metabolites, but not diuron. Diuron, DCPMU and DCA also decreased the multixenobiotic resistance (MXR) activity. Lipid peroxidation levels were increased in gill after exposure to all compounds, indicating that the original compound and diuron metabolites can induce oxidative stress in fish. The integration of all biochemical responses by the Integrated Biomarker Response (IBR) model indicated that all compounds caused significant alterations in O. niloticus, but DCPMU caused the higher alterations in both liver and gill. Our findings imply that diuron and its metabolites may impair the physiological response related to biotransformation and antioxidant activity in fish at field concentrations. Such alterations could interfere with the ability of aquatic animals to adapt to environments contaminated by

Ocean Acidification Experiments in Large-Scale Mesocosms Reveal Similar Dynamics of Dissolved Organic Matter Production and Biotransformation

Directory of Open Access Journals (Sweden)

Maren Zark

2017-09-01

Full Text Available Dissolved organic matter (DOM represents a major reservoir of carbon in the oceans. Environmental stressors such as ocean acidification (OA potentially affect DOM production and degradation processes, e.g., phytoplankton exudation or microbial uptake and biotransformation of molecules. Resulting changes in carbon storage capacity of the ocean, thus, may cause feedbacks on the global carbon cycle. Previous experiments studying OA effects on the DOM pool under natural conditions, however, were mostly conducted in temperate and coastal eutrophic areas. Here, we report on OA effects on the existing and newly produced DOM pool during an experiment in the subtropical North Atlantic Ocean at the Canary Islands during an (1 oligotrophic phase and (2 after simulated deep water upwelling. The last is a frequently occurring event in this region controlling nutrient and phytoplankton dynamics. We manipulated nine large-scale mesocosms with a gradient of pCO2 ranging from ~350 up to ~1,030 μatm and monitored the DOM molecular composition using ultrahigh-resolution mass spectrometry via Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS. An increase of 37 μmol L−1 DOC was observed in all mesocosms during a phytoplankton bloom induced by simulated upwelling. Indications for enhanced DOC accumulation under elevated CO2 became apparent during a phase of nutrient recycling toward the end of the experiment. The production of DOM was reflected in changes of the molecular DOM composition. Out of the 7,212 molecular formulae, which were detected throughout the experiment, ~50% correlated significantly in mass spectrometric signal intensity with cumulative bacterial protein production (BPP and are likely a product of microbial transformation. However, no differences in the produced compounds were found with respect to CO2 levels. Comparing the results of this experiment with a comparable OA experiment in the Swedish Gullmar Fjord, reveals

Beta-endorphin 1-31 biotransformation and cAMP modulation in inflammation.

Directory of Open Access Journals (Sweden)

Naghmeh Hajarol Asvadi

Full Text Available A large body of evidence now exists for the immune cell expression, production, and the release of beta-endorphin (BE 1-31 within inflamed tissue. The inflammatory milieu is characterised by increased acidity, temperature and metabolic activity. Within these harsh conditions BE 1-31 is even more susceptible to increased enzymatic degradation over that of plasma or other non-injured tissue. To elucidate the biotransformation pathways of BE 1-31 and provide an insight to the impact of inflamed tissue environments, BE 1-31 and three of its major N-terminal fragments (BE 1-11, BE 1-13 and BE 1-17 were incubated in inflamed tissue homogenates at pH 5.5 for 2 hrs. In addition, the potency of BE 1-31 and five main N--terminal fragments (BE 1-9, BE 1-11, BE 1-13, BE 1-17, BE 1-20 was assessed at mu-opioid receptors (MOR, delta-opioid receptors (DOR, and kappa-opioid receptors (KOR. Opioid receptor potency was investigated by examining the modulation of forskolin induced cAMP accumulation. The majority of the N-terminal fragment of BE 1-31 had similar efficacy to BE 1-31 at MOR. The shortest of the major N-terminal fragments (BE 1-9, had partial agonist activity at MOR but possessed the highest potency of all tested peptides at DOR. There was limited effect for BE 1-31 and the biotransformed peptides at KOR. Major N-terminal fragments produced within inflamed tissue have increased presence within inflamed tissue over that of the parent molecule BE 1-31 and may therefore contribute to BE 1-31 efficacy within disease states that involve inflammation.

In vitro biotransformation rates in fish liver S9: effect of dosing techniques.

Science.gov (United States)

Lee, Yung-Shan; Lee, Danny H Y; Delafoulhouze, Maximilien; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2014-08-01

In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals. © 2014 SETAC.

Biotransformation of (-)-(1R,4S)-Menthone and (+)-(1S,4R)-Menthone by the Common Cutworm Spodoptera litura Larvae.

Science.gov (United States)

Marumoto, Shinsuke; Okuno, Yoshiharu; Hagiwara, Yuki; Miyazawa, Mitsuo

2017-08-01

Using biotransformation as a biocatalytic process has the advantage of being able to proceed under mild conditions and with high regio- and enantioselectivity. This study investigated the biotransformation of (-)-(1R,4S)-menthone (1) and (+)-(1S,4R)-menthone (2) by Spodoptera litura larvae. Compound 1 was converted to (-)-(1R,4S)-7-hydroxymenthone (1-1), (+)-(1R,3S,4S)-7-hydroxyneomenthol (1-2) and (-)-(1R,4S,8R)-p-menth-3-one-9-oic acid (1-3). The metabolism of substrate 2 generated three enantiomers of the above metabolites, designated as 2-1 to 2-3, respectively. The C-9 position of (-)-menthone and (+)-menthone was oxidized to carboxylic acid by S. litura, which is a metabolic pathway not observed in any other example of biocatalysis.

Biotransformation of petroleum hydrocarbons and microbial communities in seawater with oil dispersions and copepod feces.

Science.gov (United States)

Størdal, Ingvild Fladvad; Olsen, Anders Johny; Jenssen, Bjørn Munro; Netzer, Roman; Altin, Dag; Brakstad, Odd Gunnar

2015-12-30

To determine biotransformation of components in crude oil dispersions in the presence of feces from marine copepods, dispersed oil was incubated alone, with the addition of clean or oil-containing feces. We hypothesized that the feces would contribute with nutrients to bacteria, and higher concentrations of oil-degrading bacteria, respectively. Presence of clean feces resulted in higher degradation of aromatic oil compounds, but lower degradation of n-alkanes. Presence of oil-containing feces resulted in higher degradation of n-alkanes. The effect of clean feces on aromatic compounds are suggested to be due to higher concentrations of nutrients in the seawater where aromatic degradation takes place, while the lower degradation of n-alkanes are suggested to be due to a preference by bacteria for feces over these compounds. Large aggregates were observed in oil dispersions with clean feces, which may cause sedimentation of un-weathered lipophilic oil compounds towards the seafloor if formed during oil spills. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antimicrobial Activity of Hydroxylactone obtained by Biotransformation of Bromo- and Iodolactone with Gem-Dimethylcyclohexane Ring

Energy Technology Data Exchange (ETDEWEB)

Grabarczyk, Malgorzata; Maczka, Wanda; Winska, Katarzyna; Aniol, Miroslaw, E-mail: magrab@onet.pl [Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Wroclaw (Poland); Zarowska, Barbara [Department of Biotechnology and Food Microbiology, Wroclaw University of Environmental and Life Sciences, Wroclaw (Poland)

2013-12-01

Two bicyclic lactones with gem-dimethylcyclohexane rings ({delta}-bromo-{gamma}-lactone and {delta}-iodo-{gamma}-lactone) were used as substrates for biotransformation by whole cells of several fungal strains (five cepas Fusarium, Nigrospora oryzae, Syncephalastrum racemosum, Stemphylium botryosum, Cunninghamella japonica and Acremonium sp). Some of the selected microorganisms (mainly Fusarium strains) transformed these lactones by hydrolytic dehalogenation into cis-(-)-2-hydroxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one. The conversion of the substrate was equal or close to 100%, showing that this method allows for the complete removal of the halogen atom from the molecule, replacing it by a hydroxy group. The structures of all substrates and products were established on the basis of their spectral data. Hydroxylactone obtained as http://jbcs.sbq.org.br/audiencia{sub p}df.asp?aid2=3794&nomeArquivo=v24n12a05.pdf a result of biotransformation was examined for its biological activity against bacteria, yeasts and fungi. This compound inhibits the growth of some tested microorganisms. (author)

Antimicrobial Activity of Hydroxylactone obtained by Biotransformation of Bromo- and Iodolactone with Gem-Dimethylcyclohexane Ring

International Nuclear Information System (INIS)

Grabarczyk, Małgorzata; Mączka, Wanda; Wińska, Katarzyna; Anioł, Mirosław; Żarowska, Barbara

2013-01-01

Two bicyclic lactones with gem-dimethylcyclohexane rings (δ-bromo-γ-lactone and δ-iodo-γ-lactone) were used as substrates for biotransformation by whole cells of several fungal strains (five cepas Fusarium, Nigrospora oryzae, Syncephalastrum racemosum, Stemphylium botryosum, Cunninghamella japonica and Acremonium sp). Some of the selected microorganisms (mainly Fusarium strains) transformed these lactones by hydrolytic dehalogenation into cis-(‑)-2-hydroxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one. The conversion of the substrate was equal or close to 100%, showing that this method allows for the complete removal of the halogen atom from the molecule, replacing it by a hydroxy group. The structures of all substrates and products were established on the basis of their spectral data. Hydroxylactone obtained as http://jbcs.sbq.org.br/audiencia_pdf.asp?aid2=3794&nomeArquivo=v24n12a05.pdf a result of biotransformation was examined for its biological activity against bacteria, yeasts and fungi. This compound inhibits the growth of some tested microorganisms. (author)

Aphids transform and detoxify the mycotoxin deoxynivalenol via a type II biotransformation mechanism yet unknown in animals.

Science.gov (United States)

De Zutter, N; Audenaert, K; Arroyo-Manzanares, N; De Boevre, M; Van Poucke, C; De Saeger, S; Haesaert, G; Smagghe, G

2016-12-08

Biotransformation of mycotoxins in animals comprises phase I and phase II metabolisation reactions. For the trichothecene deoxynivalenol (DON), several phase II biotransformation reactions have been described resulting in DON-glutathiones, DON-glucuronides and DON-sulfates made by glutathione-S-transferases, uridine-diphosphoglucuronyl transferases and sulfotransferases, respectively. These metabolites can be easily excreted and are less toxic than their free compounds. Here, we demonstrate for the first time in the animal kingdom the conversion of DON to DON-3-glucoside (DON-3G) via a model system with plant pathogenic aphids. This phase II biotransformation mechanism has only been reported in plants. As the DON-3G metabolite was less toxic for aphids than DON, this conversion is considered a detoxification reaction. Remarkably, English grain aphids (Sitobion avenae) which co-occur with the DON producer Fusarium graminearum on wheat during the development of fusarium symptoms, tolerate DON much better and convert DON to DON-3G more efficiently than pea aphids (Acyrthosiphon pisum), the latter being known to feed on legumes which are no host for F. graminearum. Using a non-targeted high resolution mass spectrometric approach, we detected DON-diglucosides in aphids probably as a result of sequential glucosylation reactions. Data are discussed in the light of an eventual co-evolutionary adaptation of S. avenae to DON.

Crosses between monokaryons of Pleurotus sapidus or Pleurotus florida show an improved biotransformation of (+)-valencene to (+)-nootkatone.

Science.gov (United States)

Omarini, Alejandra B; Plagemann, Ina; Schimanski, Silke; Krings, Ulrich; Berger, Ralf G

2014-11-01

Several hundred monokaryotic and new dikaryotic strains derived thereof were established from (+)-valencene tolerant Pleurotus species. When grouped according to their growth rate on agar plates and compared to the parental of Pleurotus sapidus 69, the slowly growing monokaryons converted (+)-valencene more efficiently to the grapefruit flavour compound (+)-nootkatone. The fast growing monokaryons and the slow×slow and the fast×fast dikaryotic crosses showed similar or inferior yields. Some slow×fast dikaryons, however, exceeded the biotransformation capability of the parental dikaryon significantly. The activity of the responsible enzyme, lipoxygenase, showed a weak correlation with the yields of (+)-nootkatone indicating that the determination of enzyme activity using the primary substrate linoleic acid may be misleading in predicting the biotransformation efficiency. This exploratory study indicated that a classical genetics approach resulted in altered and partly improved terpene transformation capability (plus 60%) and lipoxygenase activity of the strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chronic toxicity of polycyclic aromatic compounds to the springtail Folsomia candida and the enchytraeid Enchytraeus crypticus.

NARCIS (Netherlands)

Droge, S.T.J.; Leon Paumen, M; Bleeker, E.A.J.; Kraak, M.H.S.; van Gestel, C.A.M.

2006-01-01

An urgent need exists for incorporating heterocyclic compounds and (bio)transformation products in ecotoxicological test schemes and risk assessment of polycyclic aromatic compounds (PACs). The aim of the present study therefore was to determine the chronic effects of (heterocyclic) PACs on two

Biotransformation of selected anthelmintics in sheep tapeworm (Moniezia expansa)

OpenAIRE

Bečanová, Aneta

2013-01-01

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Aneta Bečanová Supervisor: Mgr. Hana Bártíková, Ph.D. Title of diploma thesis: Biotransformation of selected anthelmintics in sheep tapeworm (Moniezia expansa) Biotransformation of anthelmintics is a process that prevents the parasite from adverse effects of xenobiotics. Therefore, it is the main factor that causes the reduction of an anthelmintic effect, resistance development and...

Enhanced biotransformation of TCE using plant terpenoids in contaminated groundwater.

Science.gov (United States)

Brown, J R-M; Thompson, I P; Paton, G I; Singer, A C

2009-12-01

To examine plant terpenoids as inducers of TCE (trichloroethylene) biotransformation by an indigenous microbial community originating from a plume of TCE-contaminated groundwater. One-litre microcosms of groundwater were spiked with 100 micromol 1(-1) of TCE and amended weekly for 16 weeks with 20 microl 1(-1) of the following plant monoterpenes: linalool, pulegone, R-(+) carvone, S-(-) carvone, farnesol, cumene. Yeast extract-amended and unamended control treatments were also prepared. The addition of R-carvone and S-carvone, linalool and cumene resulted in the biotransformation of upwards of 88% of the TCE, significantly more than the unamendment control (61%). The aforementioned group of terpenes also significantly (P TCE to be degraded than the remaining two terpenes (farnesol and pulegone), and the yeast extract treatment which biotransformed 74-75% of the TCE. The microbial community profile was monitored by denaturing gradient gel electrophoresis and demonstrated much greater similarities between the microbial communities in terpene-amended treatments than in the yeast extract or unamended controls. TCE biotransformation can be significantly enhanced through the addition of selected plant terpenoids. Plant terpenoid and nutrient supplementation to groundwater might provide an environmentally benign means of enhancing the rate of in situ TCE bioremediation.

Biotransformation of plutonium complexed with citric acid

International Nuclear Information System (INIS)

Francis, A.J.; Dodge, C.J.; Gillow, J.B.

2006-01-01

The presence of organic ligands in radioactive wastes is a major concern because of their potential for increasing the transport of radionuclides from disposal sites. Biotransformation of radionuclides complexed with organic ligands should precipitate the radionuclides and retard their migration. We investigated the biotransformation of Pu(IV) (10 -8 to 10 -5 M), by Pseudomonas fluorescens in the presence of excess citric acid. Analysis of 242 Pu-citrate by electrospray ionization-mass spectrometry (ESI-MS) indicated the presence of biligand Pu-cit 2 as the predominant complex. XANES and EXAFS analyses showed that Pu was in the +4 oxidation state and associated with citric acid as a mononuclear complex. Citric acid was metabolized by P. fluorescens at a rate of 4.9 μM/h, but in the presence of 10 -8 and 10 -6 M Pu, this rate decreased to 4.0 and 3.8 μM/h, respectively. An increase in the ionic strength of the medium from 0.18 M to 0.9 M lowered citrate metabolism by ∝ 65%. Pu added to the growth medium in the absence of bacteria remained as Pu(IV) in solution as a complex with citric acid. However, solvent extraction by thenoyltrifluoroacetone (TTA) and microfiltration (0.03 μm) of the medium containing bacteria after citrate biodegradation revealed the presence of polymeric Pu. The extent of formation of the Pu polymer depended on the Pu: citrate ratio, the extent of citrate metabolism, and the ionic strength of the medium. (orig.)

Evaluation of the inorganic selenium biotransformation in selenium-enriched yogurt by HPLC-ICP-MS.

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Alzate, Adriana; Cañas, Benito; Pérez-Munguía, Sandra; Hernández-Mendoza, Hector; Pérez-Conde, Concepción; Gutiérrez, Ana Maria; Cámara, Carmen

2007-11-28

Selenium is an essential element in the human diet. Interestingly, there has been an increased consumption of dietary supplements containing this element in the form of either inorganic or organic compounds. The effect of using selenium as a dietary supplement in yogurt has been evaluated. For this purpose, different concentrations of inorganic Se (ranging from 0.2 to 5000 microg g(-1)) have been added to milk before the fermentation process. Biotransformation of inorganic Se into organic species has been carefully evaluated by ion-exchange, reversed-phase, or size-exclusion chromatography, coupled to inductively coupled plasma mass spectrometry (ICP-MS). Yogurt fermentation in the presence of up to 2 microg g(-1) of Se(IV) produces a complete incorporation of this element into proteins as has been demonstrated applying a dialysis procedure. Analysis by SEC-ICP-MS showed that most of them have a molecular mass in the range of 30-70 kDa. Species determination after enzymatic hydrolysis has allowed the identification of Se-cystine using two different chromatographic systems. The biotransformation process that takes place during yogurt fermentation is very attractive because yogurt can act as a source of selenium supplementation.

Biotransformation and Production from Hansenula Anomala to Natural Ethyl Phenylacetate

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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.

Synthesis of a new allelopathic agent from the biotransformation of ent-15α-hydroxy-16-kauren-19-oic acid with Fusarium proliferatum.

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Rocha, A D; Vieira, H da S; Takahashi, J A; Boaventura, M A D

2017-11-01

The use of kaurane diterpenes as substrates in fungal biotransformation to achieve bioactive compounds has been widely reported. In this work, the natural product kaurenoic acid, a diterpene widely distributed in the plant Kingdom, was chemically converted into ent-15α-hydroxy-kaur-16-en-19-oic acid (1). Substrate 1 was subjected to biotransformation by the fungus Fusarium proliferatum, furnishing a new derivative, ent-2α,15α-dihydroxy-kaur-16-en-19-oic acid (2). The structure of metabolite 2 was deduced on the basis of spectroscopy and MS data. Derivative 2 showed allelopathic activity on germination and growth of root and stem of lettuce (Lactuca sativa), inhibiting 100% of germination and growth of roots and stem, at higher concentration assayed (10 -4  mol/L).

Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

International Nuclear Information System (INIS)

Xu Jinsheng; Purcell, Wendy M.

2006-01-01

The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect the status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity

Feline hepatic biotransformation and transport mechanisms

NARCIS (Netherlands)

van Beusekom, C.D. van

2015-01-01

Hepatic biotransformation and drug transport mechanisms vary significantly between species. While these processes that determine largely the kinetic behavior of drugs have been studied abundantly in dogs, corresponding investigations in cats are hardly available, despite the increasing role of cats

Biotransformation of ferulic acid to vanillin in the packed bed-stirred fermentors.

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Yan, Lei; Chen, Peng; Zhang, Shuang; Li, Suyue; Yan, Xiaojuan; Wang, Ningbo; Liang, Ning; Li, Hongyu

2016-10-06

We performed the biotransformation of ferulic acid to vanillin using Bacillus subtilis (B. subtilis) in the stirring packed-bed reactors filled with carbon fiber textiles (CFT). Scanning electron microscope (SEM), HPLC, qRT-PCR and ATP assay indicated that vanillin biotransformation is tightly related to cell growth, cellar activity and the extent of biofilm formation. The biotransformation was affected by hydraulic retention time (HRT), temperature, initial pH, stirring speed and ferulic acid concentration, and the maximum vanillin production was obtained at 20 h, 35 °C, 9.0, 200 rpm, 1.5 g/L, respectively. Repeated batch biotransformation performed under this optimized condition showed that the maximum productivity (0.047 g/L/h) and molar yield (60.43%) achieved in immobilized cell system were 1.84 and 3.61 folds higher than those achieved in free cell system. Therefore, the stirring reactor packed with CFT carrier biofilm formed by B. subtilis represented a valid biocatalytic system for the production of vanillin.

Biotransformation of enoximone, a new cardiotonic agent, in man and laboratory animals

International Nuclear Information System (INIS)

Chan, K.Y.; Lang, J.F.; Coutant, J.E.; Okerholm, R.A.

1986-01-01

Enoximone, 1,3-dihydro-4-methyl-5-[4-(methylthio)benzoyl]-2H-imidazol-2-one is a new cardiotonic agent which is currently undergoing clinical evaluation in patients with congestive heart failure. Biotransformation of enoximone was studied in man, rat, monkey and dog by means of 14 C-labelled material, HPLC and GC/MS techniques. Metabolic conversions were qualitatively similar in all species. The parent compound was found to be extensively metabolized. Generally less than 1% of the dose was recovered as enoximone in urine. The sulfoxide was the major metabolite in all species, accounting for over 90% of the dose in the urine of the monkey and greater than 75% in man and the rat. The sulfone was present in trace quantities, except in the rats, where it accounted for 5-8% of the dose. A glycine conjugate of 4-methylthiobenzoic acid was also identified as a urinary metabolite; and the dog seems to favor this pathway more than the other 3 species; as it accounted for over 30% of the dose. The two stereoisomers of synthetic sulfoxide were separated by HPLC, and examination of urine from patients receiving enoximone therapy suggested that the metabolic conversion of enoximone to sulfoxide was stereospecific, as only one isomeric peak was observed in the HPLC system

Postnatal modulation of hepatic biotransformation system enzymes via translactational exposure of F1 mouse pups to turmeric and curcumin.

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Singh, A; Singh, S P; Bamezai, R

1995-09-04

The potential for the transfer of active principle(s) of turmeric (Curcuma longa L.) and curcumin (major pigment in turmeric) via translactational route and its modulatory influence on the hepatic biotransformation system enzymes in the lactating dams and their suckling offspring was assessed. Turmeric (4 g/kg b.w. per day) and curcumin (0.4 g/kg b.w. per day) induced significant (P curcumin (0.2 g/kg b.w. per day) could modulate hepatic GST activity (P curcumin (0.4 g/kg b.w.). The induction in hepatic biotransformation system enzymes in lactating dams and F1 progeny suggests the passage of active constituents and/or metabolites of turmeric and curcumin via the translactational route.

Green tea yogurt: major phenolic compounds and microbial growth.

Science.gov (United States)

Amirdivani, Shabboo; Baba, Ahmad Salihin Hj

2015-07-01

The purpose of this study was to evaluate fermentation of milk in the presence of green tea (Camellia sinensis) with respect to changes in antioxidant activity, phenolic compounds and the growth of lactic acid bacteria. Pasteurized full fat cow's milk and starter culture were incubated at 41 °C in the presence of two different types of green tea extracts. The yogurts formed were refrigerated (4 °C) for further analysis. The total phenolic content was highest (p yogurt (MGT) followed by steam-treated green tea (JGT) and plain yogurts. Four major compounds in MGTY and JGTY were detected. The highest concentration of major phenolic compounds in both samples was related to quercetin-rhamnosylgalactoside and quercetin-3-O-galactosyl-rhamnosyl-glucoside for MGTY and JGTY respectively during first 7 day of storage. Diphenyl picrylhydrazyl and ferric reducing antioxidant power methods showed highest antioxidant capacity in MGTY, JGTY and PY. Streptococcus thermophillus and Lactobacillus spp. were highest in MGTY followed by JGTY and PY. This paper evaluates the implementation of green tea yogurt as a new product with functional properties and valuable component to promote the growth of beneficial yogurt bacteria and prevention of oxidative stress by enhancing the antioxidant activity of yogurt.

A Monte Carlo simulation method for assessing biotransformation effects on groundwater fuel hydrocarbon plume lengths

International Nuclear Information System (INIS)

McNab, W.W. Jr.

2000-01-01

Biotransformation of dissolved groundwater hydrocarbon plumes emanating from leaking underground fuel tanks should, in principle, result in plume length stabilization over relatively short distances, thus diminishing the environmental risk. However, because the behavior of hydrocarbon plumes is usually poorly constrained at most leaking underground fuel tank sites in terms of release history, groundwater velocity, dispersion, as well as the biotransformation rate, demonstrating such a limitation in plume length is problematic. Biotransformation signatures in the aquifer geochemistry, most notably elevated bicarbonate, may offer a means of constraining the relationship between plume length and the mean biotransformation rate. In this study, modeled plume lengths and spatial bicarbonate differences among a population of synthetic hydrocarbon plumes, generated through Monte Carlo simulation of an analytical solute transport model, are compared to field observations from six underground storage tank (UST) sites at military bases in California. Simulation results indicate that the relationship between plume length and the distribution of bicarbonate is best explained by biotransformation rates that are consistent with ranges commonly reported in the literature. This finding suggests that bicarbonate can indeed provide an independent means for evaluating limitations in hydrocarbon plume length resulting from biotransformation. (Author)

Polymorphisms of genes involved in polycyclic aromatic hydrocarbons’ biotransformation and atherosclerosis

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Marinković, Natalija; Pašalić, Daria; Potočki, Slavica

2013-01-01

Polycyclic aromatic hydrocarbons (PAHs) are among the most prevalent environmental pollutants and result from the incomplete combustion of hydrocarbons (coal and gasoline, fossil fuel combustion, byproducts of industrial processing, natural emission, cigarette smoking, etc.). The first phase of xenobiotic biotransformation in the PAH metabolism includes activities of cytochrome P450 from the CYP1 family and microsomal epoxide hydrolase. The products of this biotransformation are reactive oxygen species that are transformed in the second phase through the formation of conjugates with glutathione, glucuronate or sulphates. PAH exposure may lead to PAH-DNA adduct formation or induce an inflammatory atherosclerotic plaque phenotype. Several genetic polymorphisms of genes encoded for enzymes involved in PAH biotransformation have been proven to lead to the development of diseases. Enzyme CYP P450 1A1, which is encoded by the CYP1A1 gene, is vital in the monooxygenation of lipofilic substrates, while GSTM1 and GSTT1 are the most abundant isophorms that conjugate and neutralize oxygen products. Some single nucleotide polymorphisms of the CYP1A1 gene as well as the deletion polymorphisms of GSTT1 and GSTM1 may alter the final specific cellular inflammatory respond. Occupational exposure or conditions from the living environment can contribute to the production of PAH metabolites with adverse effects on human health. The aim of this study was to obtain data on biotransformation and atherosclerosis, as well as data on the gene polymorphisms involved in biotransformation, in order to better study gene expression and further elucidate the interaction between genes and the environment. PMID:24266295

SEASONAL INFLUENCES ON PCB RETENTION AND BIOTRANSFORMATION IN FISH

Science.gov (United States)

James, Margaret O.; Kleinow, Kevin M.

2013-01-01

There is extensive evidence that fish from waters with PCB-contaminated sediments accumulate PCBs and related chemicals, and that people who eat fish from contaminated waters have higher body burdens of PCBs and PCB metabolites than those who do not. PCBs and their metabolites are potentially toxic, thus it is important to human health to understand the uptake, biotransformation and elimination of PCBs in fish, since these processes determine the extent of accumulation. The intestinal uptake of PCBs present in the diet of fish into fish tissues is a process that is influenced by the lipid composition of the diet. Biotransformation of PCBs in fish, as in mammals, facilitates elimination, although many PCB congeners are recalcitrant to biotransformation in fish and mammals. Sequential biotransformation of PCBs by cytochrome P450 and conjugation pathways is even less efficient in fish than in mammalian species, thus contributing to the retention of PCBs in fish tissues. A very important factor influencing overall PCB disposition in fish is water temperature. Seasonal changes in water temperature produce adaptive physiological and biochemical changes in fish. While uptake of PCBs from the diet is similar in fish acclimated to winter or summer temperatures, there is evidence that elimination of PCBs occurs much more slowly when the fish is acclimated at low temperatures than at warmer temperatures. Research to date suggests that the processes of elimination of PCBs are modulated by several factors in fish including seasonal changes in water temperature. Thus, the body burden of PCBs in fish from a contaminated location is likely to vary with season. PMID:23494683

Biotransformation of monoaromatic and chlorinated hydrocarbons at an aviation-gasoline spill site

International Nuclear Information System (INIS)

Wilson, B.H.; Wilson, J.T.; Kampbell, D.H.; Bledsoe, B.E.; Armstrong, J.M.

1991-01-01

Loss of petroleum products from underground storage tanks, pipelines, and accidental spills are major sources of contamination of unsaturated soils, aquifer solids, and a shallow water table aquifer under the U.S. Coast Guard Air Station at Traverse City, MI, has acclimated to the aerobic and anaerobic transformation of monoaromatic hydrocarbons (BTX) released from an aviation gasoline spill. The aquifer also exhibits reductive dechlorination of a chlorinated solvent spill adjacent to the aviation gasoline spill. The groundwater is buffered near neutrality. The aviation gasoline plume is methanogenic and the aquifer contains enough iron minerals to support significant iron solubilization. Field evidence of both aerobic and anaerobic biotransformation of monoaromatics was confirmed by laboratory studies of aquifer material obtained from the site. In the laboratory studies, the removal of the monoaromatics in the anaerobic material was rapid and compared favorable with removal in the aerobic material. The kinetics of anaerobic removal of monoaromatics in the laboratory were similar to the kinetics at field scale in the aquifer. Biotransformation of the chlorinated solvents was not observed until late in the study, when daughter products from reductive dechlorination of the chlorinated solvents were identified by GC/MS

Three sesquiterpene compounds biosynthesised from artemisinic acid using suspension-cultured cells of Averrhoa carambola (Oxalidaceae).

Science.gov (United States)

Yang, Li; Zhu, Jianhua; Song, Liyan; Shi, Xiaojian; Li, Xingyi; Yu, Rongmin

2012-01-01

A new sesquiterpene glycoside, artemisinic acid 3-β-O-β-D-glucopyranoside (3, 31.24%) and other two biotransformation products, 3-β-hydroxyartemisinic acid (2, 36.69%) and 3-β-hydroxyartemisinic acid β-D-glucopyranosyl ester (4, 7.03%), were biosynthesised after artemisinic acid (1) was administered to the cultured cells of Averrhoa carambola. The three biotransformation products were obtained for the first time by using the suspension-cultured cells of A. carambola as a new biocatalyst system, and their structures were identified on the basis of the physico-chemical properties, NMR and mass spectral analyses. The results indicate that the cultured cells of A. carambola have the abilities to hydroxylate and glycosylate sesquiterpene compounds in a regio- and stereoselective manner. Furthermore, the anti-tumour activity of compounds 3 and 4 was evaluated against K562 and HeLa cell lines. Compound 4 showed strong activity against HeLa cell line, with the IC₅₀ value of 0.56 µmol mL⁻¹.

Nitroreductase catalyzed biotransformation of CL-20

International Nuclear Information System (INIS)

Bhushan, Bharat; Halasz, Annamaria; Hawari, Jalal

2004-01-01

Previously, we reported that a salicylate 1-monooxygenase from Pseudomonas sp. ATCC 29352 biotransformed CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaaza-isowurtzitane) (C 6 H 6 N 12 O 12 ) and produced a key metabolite with mol. wt. 346Da corresponding to an empirical formula of C 6 H 6 N 10 O 8 which spontaneously decomposed in aqueous medium to produce N 2 O, NH4+, and HCOOH [Appl. Environ. Microbiol. (2004)]. In the present study, we found that nitroreductase from Escherichia coli catalyzed a one-electron transfer to CL-20 to form a radical anion (CL-20 - ) which upon initial N-denitration also produced metabolite C 6 H 6 N 10 O 8 . The latter was tentatively identified as 1,4,5,8-tetranitro-1,3a,4,4a,5,7a,8,8a-octahydro-diimidazo[4,5-b:4',5'-e] pyrazine [IUPAC] which decomposed spontaneously in water to produce glyoxal (OHCCHO) and formic acid (HCOOH). The rates of CL-20 biotransformation under anaerobic and aerobic conditions were 3.4+/-0.2 and 0.25+/-0.01nmolmin -1 mg of protein -1 , respectively. The product stoichiometry showed that each reacted CL-20 molecule produced about 1.8 nitrite ions, 3.3 molecules of nitrous oxide, 1.6 molecules of formic acid, 1.0 molecule of glyoxal, and 1.3 ammonium ions. Carbon and nitrogen products gave mass-balances of 60% and 81%, respectively. A comparative study between native-, deflavo-, and reconstituted-nitroreductase showed that FMN-site was possibly involved in the biotransformation of CL-20

Production of biovanillin by one-step biotransformation using fungus Pycnoporous cinnabarinus.

Science.gov (United States)

Tilay, Ashwini; Bule, Mahesh; Annapure, Uday

2010-04-14

The current study proposes a one-step biotransformation process for vanillin production from ferulic acid using the wild fungal strain Pycnoporous cinnabarinus belonging to the family Basidiomycete. Improvement of biotransformation conditions was performed in two steps; initially a one factor at a time method was used to investigate effects of medium composition variables (i.e., carbon, nitrogen) and environmental factors such as pH on vanillin production. Subsequently, concentrations of medium components were optimized using an orthogonal matrix method. After primary screening, glucose as carbon source and corn steep liquor and ammonium chloride as organic and inorganic nitrogen source, respectively, supported maximum biotransformation of ferulic acid to vanillin. Under statistically optimum conditions vanillin production from ferulic acid by P. cinnabarinus was 126 mg/L with a molar yield of 54%. The overall molar yield of vanillin production increased by 4 times.

Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

Directory of Open Access Journals (Sweden)

Keyller Bastos Borges

2011-01-01

Full Text Available The enantioselective biotransformation of propranolol (Prop by the endophytic fungi Phomopsis sp., Glomerella cingulata, Penicillium crustosum, Chaetomium globosum and Aspergillus fumigatus was investigated by studying the kinetics of the aromatic hydroxylation reaction with the formation of 4-hydroxypropranolol (4-OH-Prop. Both Prop enantiomers were consumed by the fungi in the biotransformation process, but the 4-hydroxylation reaction yielded preferentially (--(S-4-OH-Prop. The quantity of metabolites biosynthesized varied slightly among the evaluated endophytic fungi. These results show that all investigated endophytic fungi could be used as biosynthetic tools in biotransformation processes to obtain the enantiomers of 4-OH-Prop.

Aerobic biotransformation of 3-methylindole to ring cleavage products by Cupriavidus sp. strain KK10.

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Fukuoka, Kimiko; Ozeki, Yasuhiro; Kanaly, Robert A

2015-09-01

3-Methylindole, also referred to as skatole, is a pollutant of environmental concern due to its persistence, mobility and potential health impacts. Petroleum refining, intensive livestock production and application of biosolids to agricultural lands result in releases of 3-methylindole to the environment. Even so, little is known about the aerobic biodegradation of 3-methylindole and comprehensive biotransformation pathways have not been established. Using glycerol as feedstock, the soil bacterium Cupriavidus sp. strain KK10 biodegraded 100 mg/L of 3-methylindole in 24 h. Cometabolic 3-methylindole biodegradation was confirmed by the identification of biotransformation products through liquid chromatography electrospray ionization tandem mass spectrometry analyses. In all, 14 3-methylindole biotransformation products were identified which revealed that biotransformation occurred through different pathways that included carbocyclic aromatic ring-fission of 3-methylindole to single-ring pyrrole carboxylic acids. This work provides first comprehensive evidence for the aerobic biotransformation mechanisms of 3-methylindole by a soil bacterium and expands our understanding of the biodegradative capabilities of members of the genus Cupriavidus towards heteroaromatic pollutants.

Optimisation of α-terpineol production by limonene biotransformation using Penicillium digitatum DSM 62840.

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Tai, Ya-Nan; Xu, Min; Ren, Jing-Nan; Dong, Man; Yang, Zi-Yu; Pan, Si-Yi; Fan, Gang

2016-02-01

In this study, (R)-(+)-limonene biotransformation using three fungal strains was compared. Penicillium digitatum DSM 62840 was distinguished for its capacity to transform limonene into α-terpineol with high regioselectivity. Growth kinetics in submerged liquid culture and the effects of growth phase and contact time on biotransformation were studied using this strain. Substrate concentration, co-solvent selection, and cultivation conditions were subsequently optimised. The maximum concentration of α-terpineol (833.93 mg L(-1)) was obtained when the pre-culture medium was in medium log-phase by adding 840 mg L(-1) substrate dissolved in ethanol and cultivation was performed at 24 °C, 150 rpm, and pH 6.0 for 12 h. Addition of small amounts of (R)-(+)-limonene (84 mg L(-1)) at the start of fungal log-phase growth yielded a 1.5-fold yield of α-terpineol, indicating that the enzyme was inducible. Among these three strains tested, P. digitatum DSM 62840 was proved to be an efficient biocatalyst to transform (R)-(+)-limonene to α-terpineol. Further studies revealed that the optimal growth phase for biotransformation was in the medium log phase of this strain. The biotransformation represented a wide tolerance of temperature; α-terpineol concentration underwent no significant change at 8-32 °C. The biotransformation could also be performed using resting cells. © 2015 Society of Chemical Industry.

Biotransformation potential of phytosterols under anoxic and anaerobic conditions.

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Dykstra, C M; Giles, H D; Banerjee, S; Pavlostathis, S G

2014-01-01

The biotransformation potential of three phytosterols (campesterol, stigmasterol and β-sitosterol) under denitrifying, sulfate-reducing and fermentative/methanogenic conditions was assessed. Using a group contribution method, the standard Gibbs free energy of phytosterols was calculated and used to perform theoretical energetic calculations. The oxidation of phytosterols under aerobic, nitrate-reducing, sulfate-reducing and methanogenic conditions was determined to be energetically feasible. However, using semi-continuously fed cultures maintained at 20-22 °C over 16 weekly feeding cycles (112 days; retention time, 21 days), phytosterol removal was observed under nitrate-reducing and sulfate-reducing conditions, but not under fermentative/methanogenic conditions. Under sulfate-reducing conditions, stigmast-4-en-3-one was identified as an intermediate of phytosterol biotransformation, a reaction more likely carried out by dehydrogenases/isomerases, previously reported to act on cholesterol under both oxic and anoxic (denitrifying) conditions. Further study of the biotransformation of phytosterols under anoxic/anaerobic conditions is necessary to delineate the factors and conditions leading to enhanced phytosterol biodegradation and the development of effective biological treatment systems for the removal of phytosterols from pulp and paper wastewaters and other phytosterol-bearing waste streams.

Biotransformation of uranium and other actinides in radioactive wastes

International Nuclear Information System (INIS)

Francis, A.J.

1998-01-01

Microorganisms affect the solubility, bioavailability, and mobility of actinides in radioactive wastes. Under appropriate conditions, actinides are solubilized or stabilized by the direct enzymatic or indirect nonenzymatic actions of microorganisms. Biotransformation of various forms of uranium (ionic, inorganic, and organic complexes) by aerobic and anaerobic microorganisms has been extensively studied, whereas limited information is available on other important actinides (Th, Np, Pu, and Am). Fundamental information on the mechanisms of biotransformation of actinides by microbes under various environmental conditions will be useful in predicting the long-term performance of waste repositories and in developing strategies for waste management and remediation of contaminated sites. (orig.)

In Vitro Biotransformation of Two Human CYP3A Probe Substrates and Their Inhibition during Early Zebrafish Development.

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Verbueken, Evy; Alsop, Derek; Saad, Moayad A; Pype, Casper; Van Peer, Els M; Casteleyn, Christophe R; Van Ginneken, Chris J; Wilson, Joanna; Van Cruchten, Steven J

2017-01-22

At present, the zebrafish embryo is increasingly used as an alternative animal model to screen for developmental toxicity after exposure to xenobiotics. Since zebrafish embryos depend on their own drug-metabolizing capacity, knowledge of their intrinsic biotransformation is pivotal in order to correctly interpret the outcome of teratogenicity assays. Therefore, the aim of this in vitro study was to assess the activity of cytochrome P450 (CYP)-a group of drug-metabolizing enzymes-in microsomes from whole zebrafish embryos (ZEM) of 5, 24, 48, 72, 96 and 120 h post-fertilization (hpf) by means of a mammalian CYP substrate, i.e., benzyloxy-methyl-resorufin (BOMR). The same CYP activity assays were performed in adult zebrafish liver microsomes (ZLM) to serve as a reference for the embryos. In addition, activity assays with the human CYP3A4-specific Luciferin isopropyl acetal (Luciferin-IPA) as well as inhibition studies with ketoconazole and CYP3cide were carried out to identify CYP activity in ZLM. In the present study, biotransformation of BOMR was detected at 72 and 96 hpf; however, metabolite formation was low compared with ZLM. Furthermore, Luciferin-IPA was not metabolized by the zebrafish. In conclusion, the capacity of intrinsic biotransformation in zebrafish embryos appears to be lacking during a major part of organogenesis.

Biotransformation of phytosterols under aerobic conditions.

Science.gov (United States)

Dykstra, Christy M; Giles, Hamilton D; Banerjee, Sujit; Pavlostathis, Spyros G

2014-07-01

Phytosterols are plant-derived sterols present in pulp and paper wastewater and have been implicated in the endocrine disruption of aquatic species. Bioassays were performed to assess the effect of an additional carbon source and/or solubilizing agent on the aerobic biotransformation of a mixture of three common phytosterols (β-sitosterol, stigmasterol and campesterol). The aerobic biotransformation of the phytosterol mixture by a mixed culture developed from a pulp and paper wastewater treatment system was examined under three separate conditions: with phytosterols as the sole added carbon source, with phytosterols and dextrin as an additional carbon source, and with phytosterols added with ethanol as an additional carbon source and solubilizing agent. Significant phytosterol removal was not observed in assays set up with phytosterol powder, either with or without an additional carbon source. In contrast, all three phytosterols were aerobically degraded when added as a dissolved solution in ethanol. Thus, under the experimental conditions of this study, the bioavailability of phytosterols was limited without the presence of a solubilizing agent. The total phytosterol removal rate was linear for the first six days before re-spiking, with a rate of 0.47 mg/L-d (R(2) = 0.998). After the second spiking, the total phytosterol removal rate was linear for seven days, with a rate of 0.32 mg/L-d (R(2) = 0.968). Following the 7th day, the phytosterol removal rate markedly accelerated, suggesting two different mechanisms are involved in phytosterol biotransformation, more likely related to the production of enzyme(s) involved in phytosterol degradation, induced under different cell growth conditions. β-sitosterol was preferentially degraded, as compared to stigmasterol and campesterol, although all three phytosterols fell below detection limits by the 24th day of incubation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biotransformation in the zebrafish embryo -temporal gene transcription changes of cytochrome P450 enzymes and internal exposure dynamics of the AhR binding xenobiotic benz[a]anthracene.

Science.gov (United States)

Kühnert, Agnes; Vogs, Carolina; Seiwert, Bettina; Aulhorn, Silke; Altenburger, Rolf; Hollert, Henner; Küster, Eberhard; Busch, Wibke

2017-11-01

Not much is known about the biotransformation capability of zebrafish (Danio rerio) embryos. For understanding possible toxicity differences to adult fish, it might be crucial to understand the biotransformation of chemicals in zebrafish embryos i.e. as part of toxicokinetics. The biotransformation capabilities were analysed for two different stages of zebrafish embryos in conjunction with the internal concentrations of a xenobiotic. Zebrafish embryos of the late cleavage/early blastula period (2-26 hpf) and the early pharyngula period (26-50 hpf) were exposed for 24 h to the AhR binding compound benz[a]anthracene (BaA). Time dependent changes in cyp transcription (cyp1a, cyp1b1, cyp1c1 and cyp1c2) as well as concentration & time-dependent courses of BaA in the fish embryo and the exposure medium were analysed. Additionally, the CYP mediated formation of biotransformation products was investigated. We found correlations between transcriptional responses and the internal concentration for both exposure types. These correlations were depending on the start of the exposure i.e. the age of the exposed embryo. While no significant induction of the examined gene transcripts was observed in the first 12 h of exposure beginning in the blastula period a correlation was apparent when exposure started later i.e. in the pharyngula period. A significant induction of cyp1a was detected already after 1.5 h of BaA exposure. Gene transcripts for cyp1b1, cyp1c1 and cyp1c2 showed expressions distinctly different from cyp1a and were, in general, less inducible by BaA in both exposure windows. The toxicokinetic analysis showed that the biotransformation capability was fivefold higher in the older fish embryos. Biotransformation products of phase I reactions were found between 32 hpf and 50 hpf and were tentatively identified as benz[a]anthracene-phenol and benz[a]anthracene-dihydrodiol-epoxide. In conclusion, not only duration but also onset of exposure in relation to the

Biotransformation of Silybin and its Congeners

Czech Academy of Sciences Publication Activity Database

Křen, Vladimír; Marhol, Petr; Purchartová, Kateřina; Gabrielová, E.; Modrianský, M.

2013-01-01

Roč. 14, č. 10 (2013), s. 1009-1021 ISSN 1389-2002 R&D Projects: GA ČR(CZ) GAP301/11/0662; GA MŠk(CZ) LD11051 Institutional support: RVO:61388971 Keywords : Biotransformation * cytochrome P450 * diastereoisomers Subject RIV: CE - Biochemistry Impact factor: 3.487, year: 2013 http://www.ncbi.nlm.nih.gov/pubmed/24261705

Uptake, Translocation, and Biotransformation of Organophosphorus Esters in Wheat (Triticum aestivum L.).

Science.gov (United States)

Wan, Weining; Huang, Honglin; Lv, Jitao; Han, Ruixia; Zhang, Shuzhen

2017-12-05

The uptake, translocation and biotransformation of organophosphate esters (OPEs) by wheat (Triticum aestivum L.) were investigated by a hydroponic experiment. The results demonstrated that OPEs with higher hydrophobicity were more easily taken up by roots, and OPEs with lower hydrophobicity were more liable to be translocated acropetally. A total of 43 metabolites including dealkylated, oxidatively dechlorinated, hydroxylated, methoxylated, and glutathione-, and glucuronide- conjugated products were detected derived from eight OPEs, with diesters formed by direct dealkylation from the parent triesters as the major products, followed with hydroxylated triesters. Molecular interactions of OPEs with plant biomacromolecules were further characterized by homology modeling combined with molecular docking. OPEs with higher hydrophobicity were more liable to bind with TaLTP1.1, the most important wheat nonspecific lipid transfer protein, consistent with the experimental observation that OPEs with higher hydrophobicity were more easily taken up by wheat roots. Characterization of molecular interactions between OPEs and wheat enzymes suggested that OPEs were selectively bound to TaGST4-4 and CYP71C6v1 with different binding affinities, which determined their abilities to be metabolized and form metabolite products in wheat. This study provides both experimental and theoretical evidence for the uptake, accumulation and biotransformation of OPEs in plants.

Kombucha - functional beverage: Composition, characteristics and process of biotransformation

Directory of Open Access Journals (Sweden)

Markov Siniša L.

2003-01-01

Full Text Available Kombucha is a refreshing beverage obtained by the proces of biotransformation of sugared tea with a tea fungus. Kombucha is also frequently called "tea fungus" in the literature, although there is actually no fungus involved in the fermentation. The tea fungus is a symbiotic association of native yeasts and Acetobacteriaceae species fermenting sugared (5-10% black tea (0.2-0.5% into a kombucha beverage. After about 7-10 days incubation at room temperature, kombucha is ready. Growth patterns of tea fungus microorganisms during the biotransformation process of kombucha are not well documented. Tea fungus produces many substances, which with the supply of tea nutrients, give the drink its unusual flavour and healthy properties.

Arsenite tolerance and biotransformation potential in estuarine bacteria

Digital Repository Service at National Institute of Oceanography (India)

Nagvenkar, G.S.; Ramaiah, N.

and Acinetobacter strains. From these observations it is clear that many environmental strains are capable of quite rapid biotransformation of As. Contamination of drinking water by toxic metalloid arsenic affects thousands of people worldwide. Many environmental...

Investigation of biotransformation, sorption, and desorption of multiple chemical contaminants in pilot-scale drinking water biofilters.

Science.gov (United States)

Greenstein, Katherine E; Lew, Julia; Dickenson, Eric R V; Wert, Eric C

2018-06-01

The evolving demands of drinking water treatment necessitate processes capable of removing a diverse suite of contaminants. Biofiltration can employ biotransformation and sorption to remove various classes of chemicals from water. Here, pilot-scale virgin anthracite-sand and previously used biological activated carbon (BAC)-sand dual media filters were operated for ∼250 days to assess removals of 0.4 mg/L ammonia as nitrogen, 50-140 μg/L manganese, and ∼100 ng/L each of trace organic compounds (TOrCs) spiked into pre-ozonated Colorado River water. Anthracite achieved complete nitrification within 200 days and started removing ibuprofen at 85 days. Limited manganese (10%) removal occurred. In contrast, BAC completely nitrified ammonia within 113 days, removed all manganese at 43 days, and exhibited steady state removal of most TOrCs by 140 days. However, during the first 140 days, removal of caffeine, DEET, gemfibrozil, naproxen, and trimethoprim decreased, suggesting a shift from sorption to biotransformation. Acetaminophen and sulfamethoxazole were removed at consistent levels, with complete removal of acetaminophen achieved throughout the study; ibuprofen removal increased with time. When subjected to elevated (1 μg/L) concentrations of TOrCs, BAC removed larger masses of chemicals; with a subsequent decrease and ultimate cease in the TOrCs spike, caffeine, DEET, gemfibrozil, and trimethoprim notably desorbed. By the end of operation, anthracite and BAC exhibited equivalent quantities of biomass measured as adenosine triphosphate, but BAC harbored greater microbial diversity (examined with 16S rRNA sequencing). Improved insight was gained regarding concurrent biotransformation, sorption, and desorption of multiple organic and inorganic contaminants in pilot-scale drinking water biofilters. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biotransformation of rutin to isoquercitrin using recombinant α-L-rhamnosidase from Bifidobacterium breve.

Science.gov (United States)

Zhang, Ru; Zhang, Bian-Ling; Xie, Tao; Li, Gu-Cai; Tuo, Yi; Xiang, Yu-Ting

2015-06-01

To biotransform rutin into isoquercitrin. A α-L-rhamnosidase from Bifidobacterium breve was produced by using Escherichia coli BL21 for biotransformation of rutin to isoquercitrin. The enzyme was purified by Ni(2+)-NTA chromatography to yield a soluble protein with a specific activity of 56 U protein mg(-1). The maximum enzyme activities were at pH 6.5, 55 °C, 20 mM rutin, and 1.2 U enzyme ml(-1). Under optimal conditions, the half-life of the enzyme was 96 h. The K m and V max values were 2.2 mM, 56.4 μmol mg(-1) min(-1) and 2.1 mM, 57.5 μmol mg(-1) min(-1) using pNP-Rha and rutin as substrates, respectively. The kinetic behavior indicated that the recombinant α-L-rhamnosidase has good catalytic performance for producing isoquercitrin. 20 mM rutin was biotransformed into 18.25 and 19.87 mM isoquercitrin after 60 and 240 min. The specific biotransformation of rutin to isoquercitrin using recombinant α-L-rhamnosidase from B. breve is a feasible method for use in industrial processes.

Uptake, accumulation, and biotransformation of metal oxide nanoparticles by a marine suspension-feeder

International Nuclear Information System (INIS)

Montes, Milka O.; Hanna, Shannon K.; Lenihan, Hunter S.; Keller, Arturo A.

2012-01-01

Highlights: ► Suspension-feeding by mussels can greatly alter mobility and fate of metal oxide nanoparticles. ► Bioprocessing of metal oxide nanoparticles by mussels removes large fraction from water column. ► Mussels repackage metal oxide nanoparticles in highly concentrated pseudofeces. ► Novel biological pathway between major compartments in marine systems. ► Very different outcome for ZnO and CeO 2 nanoparticles based on their solubility. - Abstract: A growing body of evidence indicates that some engineered nanoparticles (ENPs) are toxic to organisms that perform important ecosystem services in terrestrial and aquatic ecosystems. However, toxicity can be influenced by the biotransformation of contaminants, including ENPs, as it may alter the fate and transport of these substances. In turn, fate and transport can influence their bioavailability. To understand how biotransformation influences the fate and transport of ENPs in marine ecosystems, we exposed suspension-feeding mussels, Mytilus galloprovincialis, to two common nano-metal oxides, CeO 2 and ZnO, over a range of concentrations from 1 mg L −1 to 10 mg L −1 , in a laboratory experiment. Mussels exposed to 10 mg L −1 accumulated 62 μg g −1 of Ce and 880 μg g −1 of Zn on a dry tissue basis but rejected 21,000 μg g −1 for Ce and 63,000 μg g −1 for Zn in pseudofeces. Scanning electron microscope evidence indicates CeO 2 remained as ENPs but ZnO did not after being rejected by the mussels. Mussels filtered most of the CeO 2 from the aqueous media, while a significant fraction of Zn remained in solution. Differences in ENP solubility affect ENP uptake, excretion, and accumulation in mussels. Our study highlights the potential role of marine suspension feeders in biotransformation of ENPs.

Characterization of new recombinant 3-ketosteroid-Δ1-dehydrogenases for the biotransformation of steroids.

Science.gov (United States)

Wang, Xiaojun; Feng, Jinhui; Zhang, Dalong; Wu, Qiaqing; Zhu, Dunming; Ma, Yanhe

2017-08-01

3-Ketosteroid-Δ 1 -dehydrogenases (KstDs [EC 1.3.99.4]) catalyze the Δ 1 -dehydrogenation of steroids and are a class of important enzymes for steroid biotransformations. In this study, we cloned 12 putative KstD-encoding (kstd) genes from both fungal and Gram-positive microorganisms and attempted to overproduce the recombinant proteins in E. coli BL21(DE3). Five successful recombinant enzymes catalyzed the Δ 1 -desaturation of a variety of steroidal compounds such as 4-androstene-3,17-dione (AD), 9α-hydroxy-4-androstene-3,17-dione (9-OH-AD), hydrocortisone, cortisone, and cortexolone. However, the substrate specificity and catalytic efficiency of the enzymes differ depending on their sources. The purified KstD from Mycobacterium smegmatis mc 2 155 (MsKstD1) displayed high catalytic efficiency toward hydrocortisone, progesterone, and 9-OH-AD, where it had the highest affinity (K m 36.9 ± 4.6 μM) toward 9-OH-AD. On the other hand, the KstD from Rhodococcus erythropolis WY 1406 (ReKstD) exhibited high catalytic efficiency toward androst-4,9(11)-diene-3,17-dione (Diene), 21-acetoxy-pregna-4,9(11),16-triene-3,20-dione (Triene), and cortexolone, where in all three cases the K m values (12.3 to 17.8 μM) were 2.5-4-fold lower than that toward hydrocortisone (46.3 μM). For both enzymes, AD was a good substrate although ReKstD had a 3-fold higher affinity than MsKstD1. Reaction conditions were optimized for the biotransformation of AD or hydrocortisone in terms of pH, temperature, and effects of hydrogen peroxide, solvent, and electron acceptor. For the biotransformation of hydrocortisone with 20 g/L wet resting E. coli cells harboring MsKstD1 enzyme, the yield of prednisolone was about 90% within 3 h at the substrate concentration of 6 g/L, demonstrating the application potential of the newly cloned KstDs.

Research Progress of Natural Product Gentiopicroside - a Secoiridoid Compound.

Science.gov (United States)

Wu, Shaoping; Ning, Yaoyao; Zhao, Yingyong; Sun, Wenji; Thorimbert, Serge; Dechoux, Luc; Sollogoub, Matthieu; Zhang, Yongmin

2017-01-01

Gentiopicroside is a secoiridoid compound isolated from Gentiana lutea which is called Qin Jiao in Chinese. It is one of the most common herbal medicines used in China. In this article, we review the pharmacological and biological activity (antiviral, anti-inflammatory, analgesia, antihepatotoxic and choleretic), as well as biotransformation of the gentiopicroside. In addition, attempt towards the total synthesis of gentiopicroside is also presented.

Biotransformation, distribution and toxicity of carbon disulfide in immature rats

International Nuclear Information System (INIS)

Green, E.C.

1984-01-01

The 24-hour LD-50 values of CS 2 in 1-, 5-, 10-, 20-, 30-, and 40-day-old rats were 583, 974, 1119, 1545, 1237, and 1183 mg/kg, respectively. Twenty-four hours after CS 2 exposure, decreases in aniline hydroxylation and cytochrome P-450 were observed in rats older than one day of age. Hepatic microsomes from rats of all ages biotransformed CS 2 to COS in vitro in the presence of NADPH. Inhibition of the hepatic mixed-function oxidase enzyme system (HMFOES) was observed after incubation of hepatic microsomes from rats as young as one day of age with CS 2 and NADPH. Studies with radiolabelled CS 2 showed that a covalently binding sulfur metabolite, free from the carbon atom of CS 2 , was formed in vitro during the metabolism of CS 2 to COS which appeared to be responsible for the inhibition of the HMFOES. Three hours after 14 C-CS 2 administration in vivo to rats, between 58 and 83% of the dose of 14 C-CS 2 was expired; 4-9% of the dose was expired as 14 C-CO 2 depending on age. One to 2% of the dose of 14 C-CS 2 , and 1 to 6% of the dose of 35 S-CS 2 remained as biotransformation products in tissues. Biotransformation products of CS 2 were identified as either acid-labile or covalently bound. The results of the study implicated CS 2 biotransformation to sulfur metabolites as an important mechanism of CS 2 toxicity, particularly to 1-day-old rats which had the lowest capacity to eliminate these metabolites

Biotransformation of isoimperatorin and imperatorin by Glomerella cingulata and beta-secretase inhibitory activity.

Science.gov (United States)

Marumoto, Shinsuke; Miyazawa, Mitsuo

2010-01-01

Biotransformation studies conducted on the furanocoumarins isoimperatorin (1) and imperatorin (3) have revealed that 1 was metabolized by Glomerella cingulata to give the corresponding reduced acid, 6,7-furano-5-prenyloxy hydrocoumaric acid (2), and 3 was transformed by G. cingulata to give the dealkylated metabolite, xanthotoxol (4) in high yields (83% and 81%), respectively. The structures of the new compound 2 have been established on the basis of spectral data. The metabolites 2 and 4 were tested for the beta-secretase (BACE1) inhibitory activity in vitro, and metabolite 2 slightly inhibited the beta-secretase activity with an IC(50) value of 185.6+/-6.8 microM. The metabolite 4 was less potent activity than compounds 1-3. In addition, methyl ester (2Me), methyl ether (2a) and methyl ester and ether (2aMe) of 2 were synthesized, and investigated for the ability to inhibit beta-secretase. Compound 2aMe exhibited the best beta-secretase inhibitory activity at the IC(50) value 16.2+/-1.2 microM and found to be the 2aMe showed competitive mode of inhibition against beta-secretase with K(i) value 11.3+/-2.8 microM. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

In Vitro Biotransformation of Two Human CYP3A Probe Substrates and Their Inhibition during Early Zebrafish Development

Directory of Open Access Journals (Sweden)

Evy Verbueken

2017-01-01

Full Text Available At present, the zebrafish embryo is increasingly used as an alternative animal model to screen for developmental toxicity after exposure to xenobiotics. Since zebrafish embryos depend on their own drug-metabolizing capacity, knowledge of their intrinsic biotransformation is pivotal in order to correctly interpret the outcome of teratogenicity assays. Therefore, the aim of this in vitro study was to assess the activity of cytochrome P450 (CYP—a group of drug-metabolizing enzymes—in microsomes from whole zebrafish embryos (ZEM of 5, 24, 48, 72, 96 and 120 h post-fertilization (hpf by means of a mammalian CYP substrate, i.e., benzyloxy-methyl-resorufin (BOMR. The same CYP activity assays were performed in adult zebrafish liver microsomes (ZLM to serve as a reference for the embryos. In addition, activity assays with the human CYP3A4-specific Luciferin isopropyl acetal (Luciferin-IPA as well as inhibition studies with ketoconazole and CYP3cide were carried out to identify CYP activity in ZLM. In the present study, biotransformation of BOMR was detected at 72 and 96 hpf; however, metabolite formation was low compared with ZLM. Furthermore, Luciferin-IPA was not metabolized by the zebrafish. In conclusion, the capacity of intrinsic biotransformation in zebrafish embryos appears to be lacking during a major part of organogenesis.

A bibliometric analysis of research updates and tendencies on steroid biotransformation

Science.gov (United States)

Song, Zhaoyu

2018-03-01

Steroid biotransformation, as a powerful tool for generation of steroid active pharmaceutical ingredients and key intermediates, has received widespread attention with increasing market demand for steroid-based drugs. In our study, a bibliometric analysis of steroid biotransformation was performed to trace the research updates and tendencies from 1993 to 2016, based on the Science Citation Index Expanded (SCIE) database. Results showed a notable growth trend in publication outputs. Although the USA was the most productive country between 1993 and 2016, developing nations, including China and India, contributed the prominent growth in recent years (2005–2016). Steroids was the leading journal in this field, and the research outputs had notably increased in the field of ‘Chemistry’, ‘Pharmacology and Pharmacy’ and ‘Biotechnology and Applied Microbiology’. Finally, research focused mainly on the efficient production of novel steroid active pharmaceutical ingredients and key intermediates through steroid biotransformation. Furthermore, cytochrome P450 involved in the side-chain oxidation of sterols has gradually become a hotspot issue in recent years.

Effect of alkyl side chain location and cyclicity on the aerobic biotransformation of naphthenic acids.

Science.gov (United States)

Misiti, Teresa M; Tezel, Ulas; Pavlostathis, Spyros G

2014-07-15

Aerobic biodegradation of naphthenic acids is of importance to the oil industry for the long-term management and environmental impact of process water and wastewater. The effect of structure, particularly the location of the alkyl side chain as well as cyclicity, on the aerobic biotransformation of 10 model naphthenic acids (NAs) was investigated. Using an aerobic, mixed culture, enriched with a commercial NA mixture (NA sodium salt; TCI Chemicals), batch biotransformation assays were conducted with individual model NAs, including eight 8-carbon isomers. It was shown that NAs with a quaternary carbon at the α- or β-position or a tertiary carbon at the β- and/or β'-position are recalcitrant or have limited biodegradability. In addition, branched NAs exhibited lag periods and lower degradation rates than nonbranched or simple cyclic NAs. Two NA isomers used in a closed bottle, aerobic biodegradation assay were mineralized, while 21 and 35% of the parent compound carbon was incorporated into the biomass. The NA biodegradation probability estimated by two widely used models (BIOWIN 2 and 6) and a recently developed model (OCHEM) was compared to the biodegradability of the 10 model NAs tested in this study as well as other related NAs. The biodegradation probability estimated by the OCHEM model agreed best with the experimental data and was best correlated with the measured NA biodegradation rate.

Highly Selective Bioconversion of Ginsenoside Rb1 to Compound K by the Mycelium of Cordyceps sinensis under Optimized Conditions

Directory of Open Access Journals (Sweden)

Wei-Nan Wang

2015-10-01

Full Text Available Compound K (CK, a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that Cordyceps sinensis was a potent biocatalyst for the biotransformation of ginsenoside Rb1 into CK. After a series of investigations on the biotransformation parameters, an optimal composition of the biotransformation culture was found to be lactose, soybean powder and MgSO4 without controlling the pH. Also, an optimum temperature of 30 °C for the biotransformation process was suggested in a range of 25 °C–50 °C. Then, a biotransformation pathway of Rb1 → Rd → F2 → CK was established using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS. Our results demonstrated that the molar bioconversion rate of Rb1 to CK was more than 82% and the purity of CK produced by C. sinensis under the optimized conditions was more than 91%. In conclusion, the combination of C. sinensis and the optimized conditions is applicable for the industrial preparation of CK for medicinal purposes.

RESEARCH OF BIOTRANSFORMATION PROCESS OF CONTAINING SUGAR RAW FOR ISOMALTULOSE RECEIVING

Directory of Open Access Journals (Sweden)

O. S. Korneeva

2014-01-01

Full Text Available The process of biotransformation containing sugar raw isomaltulosesynthase bacteria of the genus Erwinia to produce isomaltulose - natural sugars substitute. Raw cane sugar, beet molasses and sweet sorghum syrup used for isomaltulose. It was established that cane sugar may serve as a substrate for the enzymatic reaction together with biotransformation of pure sucrose. Yield of isomaltulose in the transformation of raw sugar was comparable to the control and was 97% for 3,5 hours at the optimal isomerization conditions (pH 6,0, 30 º C, the enzyme dosage of 5 U / mg of sucrose. Scientifically substantiated reasons for reducing the degree of transformation of molasses, sugar syrup strength sorghum. The influence of non-sugars accompanying basic substrates - raw cane sugar, molasses, sweet sorghum syrup, when biocatalytic transformation. Proved inhibitory effect of metal ion (aluminum , iron , anions of inorganic acids ( nitrate , chloride, phosphate , amino acids (serine , aspartic acid -hand , organic acids ( citric acid, acetic acid, the process of biotransformation , the formation of sucrose. Reducing the degree of isomerization in the presence of sucrose was observed in the study of non-sugars from 50 to 65 % compared with the control. Isomaltulosesynthase activating effect on , and consequently , the yield of isomaltulose to set calcium and manganese in the form of their sulfates. The introduction of these components into a solution of pure sucrose increases the yield of isomaltulose by 30.5 and 13.2 % respectively. The data obtained will be the basis of studies to optimize the process of biotransformation of various sources of vegetable raw materials rich in sucrose to produce isomaltulose.

Anaerobic Biotransformation and Mobility of Pu and Pu-EDTA

International Nuclear Information System (INIS)

Bolton, H. Jr.; Rai, D.; Xun, L.

2005-01-01

The complexation of radionuclides (e.g., plutonium (Pu) and 60 Co) by codisposed ethylenediaminetetraacetate (EDTA) has enhanced their transport in sediments at DOE sites. Our previous NABIR research investigated the aerobic biodegradation and biogeochemistry of Pu(IV)-EDTA. Plutonium(IV) forms stable complexes with EDTA under aerobic conditions and an aerobic EDTA degrading bacterium can degrade EDTA in the presence of Pu and decrease Pu mobility. However, our recent studies indicate that while Pu(IV)-EDTA is stable in simple aqueous systems, it is not stable in the presence of relatively soluble Fe(III) compounds (i.e., Fe(OH) 3 (s)--2-line ferrihydrite). Since most DOE sites have Fe(III) containing sediments, Pu(IV) in likely not the mobile form of Pu-EDTA in groundwater. The only other Pu-EDTA complex stable in groundwater relevant to DOE sites would be Pu(III)-EDTA, which only forms under anaerobic conditions. Research is therefore needed in this brand new project to investigate the biotransformation of Pu and Pu-EDTA under anaerobic conditions. The biotransformation of Pu and Pu-EDTA under various anaerobic regimes is poorly understood including the reduction kinetics of Pu(IV) to Pu(III) from soluble (Pu(IV)-EDTA) and insoluble Pu(IV) as PuO2(am) by metal reducing bacteria, the redox conditions required for this reduction, the strength of the Pu(III)-EDTA complex, how the Pu(III)-EDTA complex competes with other dominant anoxic soluble metals (e.g., Fe(II)), and the oxidation kinetics of Pu(III)-EDTA. Finally, the formation of a stable soluble Pu(III)-EDTA complex under anaerobic conditions would require degradation of the EDTA complex to limit Pu(III) transport in geologic environments. Anaerobic EDTA degrading microorganisms have not been isolated. These knowledge gaps preclude the development of a mechanistic understanding of how anaerobic conditions will influence Pu and Pu-EDTA fate and transport to assess, model, and design approaches to stop Pu

Application of passive dosing to study the biotransformation and biodegradation of hydrophobic compounds

DEFF Research Database (Denmark)

Smith, E. C.; Rein, Arno; Trapp, Stefan

2011-01-01

Achieving well-defined and constant dissolved concentrations of hydrophobic compounds is challenging due to volatilization or sorptive losses. With passive dosing, continual partitioning into the test medium of compound(s) loaded in a polymer compensates for losses, and provides defined and const...

Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment.

Science.gov (United States)

Lo, Justin C; Allard, Gayatri N; Otton, S Victoria; Campbell, David A; Gobas, Frank A P C

2015-12-01

In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 μM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin-film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery-based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery-based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances. © 2015 SETAC.

Consequences of bile salt biotransformations by intestinal bacteria

Science.gov (United States)

Ridlon, Jason M.; Harris, Spencer C.; Bhowmik, Shiva; Kang, Dae-Joong; Hylemon, Phillip B.

2016-01-01

ABSTRACT Emerging evidence strongly suggest that the human “microbiome” plays an important role in both health and disease. Bile acids function both as detergents molecules promoting nutrient absorption in the intestines and as hormones regulating nutrient metabolism. Bile acids regulate metabolism via activation of specific nuclear receptors (NR) and G-protein coupled receptors (GPCRs). The circulating bile acid pool composition consists of primary bile acids produced from cholesterol in the liver, and secondary bile acids formed by specific gut bacteria. The various biotransformation of bile acids carried out by gut bacteria appear to regulate the structure of the gut microbiome and host physiology. Increased levels of secondary bile acids are associated with specific diseases of the GI system. Elucidating methods to control the gut microbiome and bile acid pool composition in humans may lead to a reduction in some of the major diseases of the liver, gall bladder and colon. PMID:26939849

Incremental improvements to the trout S9 biotransformation assay

Science.gov (United States)

In vitro substrate depletion methods have been used in conjunction with computational models to predict biotransformation impacts on chemical accumulation by fish. There is a consistent trend, however, toward overestimation of measured chemical residues resulting from controlled...

Evaluation of hepatic biotransformation of polybrominated diphenyl ethers in the polar bear (Ursus maritimus).

Science.gov (United States)

Krieger, Lisa K; Szeitz, András; Bandiera, Stelvio M

2016-03-01

Polar bears are at the top of the Arctic marine food chain and are subject to exposure and bioaccumulation of environmental chemicals of concern such as polybrominated diphenyl ethers (PBDEs), which were widely used as flame retardants. The aim of the present study was to evaluate the in vitro oxidative metabolism of 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) and 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) by polar bear liver microsomes. The identification and quantification of the hydroxy-brominated diphenyl ethers formed were assessed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method. Incubation of BDE-47 with archived individual liver microsomes, prepared from fifteen polar bears from northern Canada, produced a total of eleven hydroxylated metabolites, eight of which were identified using authentic standards. The major metabolites were 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether and 5'-hydroxy-2,2',4,4'-tetrabromodiphenyl ether. Incubation of BDE-99 with polar bear liver microsomes produced a total of eleven hydroxylated metabolites, seven of which were identified using authentic standards. The major metabolites were 2,4,5-tribromophenol and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. Among the CYP specific antibodies tested, anti-rat CYP2B was found to be the most active in inhibiting the formation of hydroxylated metabolites of both BDE-47 and BDE-99, indicating that CYP2B was the major CYP enzyme involved in the oxidative biotransformation of these two congeners. Our study shows that polar bears are capable of forming multiple hydroxylated metabolites of BDE-47 and BDE-99 in vitro and demonstrates the role of CYP2B in the biotransformation and possibly in the toxicity of BDE-47 and BDE-99 in polar bears. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibition of nicotine-DNA adduct formation by polyphenolic compounds in vitro

International Nuclear Information System (INIS)

Cheng Yan; Wang Haifang; Sun Hongfang; Li Hongli

2004-01-01

Nicotine[3-(1-methyl-2-pyrrolidinyl)-pyridine], a major alkaloid in tobacco products, has proven to be a potential genotoxic compound. Some polyphenolic compounds can suppress the DNA adduction, and hence act as the potential inhibitors of carcinogenesis. In this study, the inhibitory effects of three polyphenolic compounds, curcumin (diferuloylmethane), resveratrol (trans-3, 5, 4-trihydroxystilbene) and tea polyphenols, on the nicotine-DNA adduction have been investigated in vitro using radiolabelled nicotine and liquid scintillation counting (LSC) technique. Also, the inhibition mechanism of these chemopreventive agents in regard to the activity of the biotransformation enzymes, including cytochrome P450 (CYP450), cytochrome b 5 (CYb 5 ) and glutathione S-transferase (GST), has been studied. The results demonstrated that these three polyphenols induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the controls. The elimination rate of adducts reached above 46% at the highest dose for all the three agents with 51.6% for resveratrol. Correspondingly, three polyphenols all suppressed CYP450 and CYb 5 , whereas curcumin and resveratrol induced GST. The authors may arrive at a point that the three polyphenols are beneficial to prevent the nicotine adduct formation, and thus may be used to block the potential carcinogenesis induced by nicotine. (authors)

A framework for establishing predictive relationships between specific bacterial 16S rRNA sequence abundances and biotransformation rates.

Science.gov (United States)

Helbling, Damian E; Johnson, David R; Lee, Tae Kwon; Scheidegger, Andreas; Fenner, Kathrin

2015-03-01

The rates at which wastewater treatment plant (WWTP) microbial communities biotransform specific substrates can differ by orders of magnitude among WWTP communities. Differences in taxonomic compositions among WWTP communities may predict differences in the rates of some types of biotransformations. In this work, we present a novel framework for establishing predictive relationships between specific bacterial 16S rRNA sequence abundances and biotransformation rates. We selected ten WWTPs with substantial variation in their environmental and operational metrics and measured the in situ ammonia biotransformation rate constants in nine of them. We isolated total RNA from samples from each WWTP and analyzed 16S rRNA sequence reads. We then developed multivariate models between the measured abundances of specific bacterial 16S rRNA sequence reads and the ammonia biotransformation rate constants. We constructed model scenarios that systematically explored the effects of model regularization, model linearity and non-linearity, and aggregation of 16S rRNA sequences into operational taxonomic units (OTUs) as a function of sequence dissimilarity threshold (SDT). A large percentage (greater than 80%) of model scenarios resulted in well-performing and significant models at intermediate SDTs of 0.13-0.14 and 0.26. The 16S rRNA sequences consistently selected into the well-performing and significant models at those SDTs were classified as Nitrosomonas and Nitrospira groups. We then extend the framework by applying it to the biotransformation rate constants of ten micropollutants measured in batch reactors seeded with the ten WWTP communities. We identified phylogenetic groups that were robustly selected into all well-performing and significant models constructed with biotransformation rates of isoproturon, propachlor, ranitidine, and venlafaxine. These phylogenetic groups can be used as predictive biomarkers of WWTP microbial community activity towards these specific

Biotransformations of organic energetic materials

International Nuclear Information System (INIS)

Matousek, J.

2001-01-01

This paper reviews data on the acute eco-toxicity and delayed effects (mutagenicity) of the model substance (TNT) and of a wide spectrum of its biodegradation products in the wastewaters. It also suggests main metabolic pathways of biotransformation, involving biological reduction. Some possibilities of remediation of contaminated soils utilising microbial catabolic pathways leading to the hydroxy derivatives and up to the cleavage of the aromatic ring system in the presence of the soil bacteria Pseudomonas fluorescens are shown, as well as the practical utilisation of fungi Phanerochaete chrysosporium under aerobic conditions

High-throughput transcriptome sequencing analysis provides preliminary insights into the biotransformation mechanism of Rhodopseudomonas palustris treated with alpha-rhamnetin-3-rhamnoside.

Science.gov (United States)

Bi, Lei; Guan, Chun-jie; Yang, Guan-e; Yang, Fei; Yan, Hong-yu; Li, Qing-shan

2016-04-01

The purple photosynthetic bacterium Rhodopseudomonas palustris has been widely applied to enhance the therapeutic effects of traditional Chinese medicine using novel biotransformation technology. However, comprehensive studies of the R. palustris biotransformation mechanism are rare. Therefore, investigation of the expression patterns of genes involved in metabolic pathways that are active during the biotransformation process is essential to elucidate this complicated mechanism. To promote further study of the biotransformation of R. palustris, we assembled all R. palustris transcripts using Trinity software and performed differential expression analysis of the resulting unigenes. A total of 9725, 7341 and 10,963 unigenes were obtained by assembling the alpha-rhamnetin-3-rhamnoside-treated R. palustris (RPB) reads, control R. palustris (RPS) reads and combined RPB&RPS reads, respectively. A total of 9971 unigenes assembled from the RPB&RPS reads were mapped to the nr, nt, Swiss-Prot, Gene Ontology (GO), Clusters of Orthologous Groups (COGs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) (E-value biotransformation in R. palustris. Furthermore, we propose two putative ARR biotransformation mechanisms in R. palustris. These analytical results represent a useful genomic resource for in-depth research into the molecular basis of biotransformation and genetic modification in R. palustris. Copyright © 2016 Elsevier GmbH. All rights reserved.

The potential of cloud point system as a novel two-phase partitioning system for biotransformation.

Science.gov (United States)

Wang, Zhilong

2007-05-01

Although the extractive biotransformation in two-phase partitioning systems have been studied extensively, such as the water-organic solvent two-phase system, the aqueous two-phase system, the reverse micelle system, and the room temperature ionic liquid, etc., this has not yet resulted in a widespread industrial application. Based on the discussion of the main obstacles, an exploitation of a cloud point system, which has already been applied in a separation field known as a cloud point extraction, as a novel two-phase partitioning system for biotransformation, is reviewed by analysis of some topical examples. At the end of the review, the process control and downstream processing in the application of the novel two-phase partitioning system for biotransformation are also briefly discussed.

Structural Characterization of Silica Particles Extracted from Grass Stenotaphrum secundatum: Biotransformation via Annelids

Directory of Open Access Journals (Sweden)

A. Espíndola-Gonzalez

2014-01-01

Full Text Available This study shows the structural characterization of silica particles extracted from Stenotaphrum secundatum (St. Augustine grass using an annelid-based biotransformation process. This bioprocess starts when St. Augustine grass is turned into humus by vermicompost, and then goes through calcination and acid treatment to obtain silica particles. To determine the effect of the bioprocess, silica particles without biotransformation were extracted directly from the sample of grass. The characterization of the silica particles was performed using Infrared (FTIR and Raman spectroscopy, Transmission Electron Microscopy (TEM, X-ray Diffraction (XRD, Dynamic Light Scattering (DLS, and Energy Dispersion Spectroscopy (EDS. Both types of particles showed differences in morphology and size. The particles without biotransformation were essentially amorphous while those obtained via annelids showed specific crystalline phases. The biological relationship between the metabolisms of worms and microorganisms and the organic-mineral matter causes changes to the particles' properties. The results of this study are important because they will allow synthesis of silica in cheaper and more ecofriendly ways.

Developmental and genetic modulation of arsenic biotransformation: A gene by environment interaction?

International Nuclear Information System (INIS)

Meza, Mercedes; Gandolfi, A. Jay; Klimecki, Walter T.

2007-01-01

The complexity of arsenic toxicology has confounded the identification of specific pathways of disease causation. One focal point of arsenic research is aimed at fully characterizing arsenic biotransformation in humans, a process that appears to be quite variable, producing a mixture of several arsenic species with greatly differing toxic potencies. In an effort to characterize genetic determinants of variability in arsenic biotransformation, a genetic association study of 135 subjects in western Sonora, Mexico was performed by testing 23 polymorphic sites in three arsenic biotransformation candidate genes. One gene, arsenic 3 methyltransferase (AS3MT), was strongly associated with the ratio of urinary dimethylarsinic acid to monomethylarsonic acid (D/M) in children (7-11 years) but not in adults (18-79 years). Subsequent analyses revealed that the high D/M values associated with variant AS3MT alleles were primarily due to lower levels of monomethylarsonic acid as percent of total urinary arsenic (%MMA5). In light of several reports of arsenic-induced disease being associated with relatively high %MMA5 levels, these findings raise the possibility that variant AS3MT individuals may suffer less risk from arsenic exposure than non-variant individuals. These analyses also provide evidence that, in this population, regardless of AS3MT variant status, children tend to have lower %MMA5 values than adults, suggesting that the global developmental regulation of arsenic biotransformation may interact with genetic variants in metabolic genes to result in novel genetic effects such as those in this report

The participation of human hepatic P450 isoforms, flavin-containing monooxygenases and aldehyde oxidase in the biotransformation of the insecticide fenthion

International Nuclear Information System (INIS)

Leoni, Claudia; Buratti, Franca M.; Testai, Emanuela

2008-01-01

Although fenthion (FEN) is widely used as a broad spectrum insecticide on various crops in many countries, very scant data are available on its biotransformation in humans. In this study the in vitro human hepatic FEN biotransformation was characterized, identifying the relative contributions of cytochrome P450 (CYPs) and/or flavin-containing monooxygenase (FMOs) by using single c-DNA expressed human enzymes, human liver microsomes and cytosol and CYP/FMO-specific inhibitors. Two major metabolites, FEN-sulfoxide and FEN-oxon (FOX), are formed by some CYPs although at very different levels, depending on the relative CYP hepatic content. Formation of further oxidation products and the reduction of FEN-sulfoxide back to FEN by the cytosolic aldehyde oxidase enzyme were ruled out. Comparing intrinsic clearance values, FOX formation seemed to be favored and at low FEN concentrations CYP2B6 and 1A2 are mainly involved in its formation. At higher levels, a more widespread CYP involvement was evident, as in the case of FEN-sulfoxide, although a higher efficiency of CYP2C family was suggested. Hepatic FMOs were able to catalyze only sulfoxide formation, but at low FEN concentrations hepatic FEN sulfoxidation is predominantly P450-driven. Indeed, the contribution of the hepatic isoforms FMO 3 and FMO 5 was generally negligible, although at high FEN concentrations FMO's showed activities comparable to the active CYPs, accounting for up to 30% of total sulfoxidation. Recombinant FMO 1 showed the highest efficiency with respect to CYPs and the other FMOs, but it is not expressed in the adult human liver. This suggests that FMO 1 -catalysed sulfoxidation may represent the major extra-hepatic pathway of FEN biotransformation

Uptake, accumulation, and biotransformation of metal oxide nanoparticles by a marine suspension-feeder

Energy Technology Data Exchange (ETDEWEB)

Montes, Milka O. [University of California Center for Environmental Implications of Nanotechnology, Bren School of Environmental Science and Management, University of California, Santa Barbara, CA 93106 (United States); University of Texas of the Permian Basin, 4901 E. University, Odessa, TX 79762 (United States); Hanna, Shannon K.; Lenihan, Hunter S. [University of California Center for Environmental Implications of Nanotechnology, Bren School of Environmental Science and Management, University of California, Santa Barbara, CA 93106 (United States); Keller, Arturo A., E-mail: keller@bren.ucsb.edu [University of California Center for Environmental Implications of Nanotechnology, Bren School of Environmental Science and Management, University of California, Santa Barbara, CA 93106 (United States)

2012-07-30

Highlights: Black-Right-Pointing-Pointer Suspension-feeding by mussels can greatly alter mobility and fate of metal oxide nanoparticles. Black-Right-Pointing-Pointer Bioprocessing of metal oxide nanoparticles by mussels removes large fraction from water column. Black-Right-Pointing-Pointer Mussels repackage metal oxide nanoparticles in highly concentrated pseudofeces. Black-Right-Pointing-Pointer Novel biological pathway between major compartments in marine systems. Black-Right-Pointing-Pointer Very different outcome for ZnO and CeO{sub 2} nanoparticles based on their solubility. - Abstract: A growing body of evidence indicates that some engineered nanoparticles (ENPs) are toxic to organisms that perform important ecosystem services in terrestrial and aquatic ecosystems. However, toxicity can be influenced by the biotransformation of contaminants, including ENPs, as it may alter the fate and transport of these substances. In turn, fate and transport can influence their bioavailability. To understand how biotransformation influences the fate and transport of ENPs in marine ecosystems, we exposed suspension-feeding mussels, Mytilus galloprovincialis, to two common nano-metal oxides, CeO{sub 2} and ZnO, over a range of concentrations from 1 mg L{sup -1} to 10 mg L{sup -1}, in a laboratory experiment. Mussels exposed to 10 mg L{sup -1} accumulated 62 {mu}g g{sup -1} of Ce and 880 {mu}g g{sup -1} of Zn on a dry tissue basis but rejected 21,000 {mu}g g{sup -1} for Ce and 63,000 {mu}g g{sup -1} for Zn in pseudofeces. Scanning electron microscope evidence indicates CeO{sub 2} remained as ENPs but ZnO did not after being rejected by the mussels. Mussels filtered most of the CeO{sub 2} from the aqueous media, while a significant fraction of Zn remained in solution. Differences in ENP solubility affect ENP uptake, excretion, and accumulation in mussels. Our study highlights the potential role of marine suspension feeders in biotransformation of ENPs.

Modulation of hepatic biotransformation and biliary excretion of bile acid by age and sinusoidal bile acid load

International Nuclear Information System (INIS)

Baumgartner, U.; Miyai, K.; Hardison, W.G.M.

1987-01-01

Pericentral hepatocytes excrete bile acids more slowly and biotransform them more than periportal cells. This may reflect adaptation to low pericentral bile acid concentration or may be intrinsic. The authors studied two models in which pericentral bile acid concentrations are high: the 72-h choledocho-caval shunt (CCS) rat and the 3- to 4-wk-old rat. Livers were perfused forward or backward to assess periportal or pericentral hepatocyte function. Taurodeoxycholate (TDC) was infused at 32 nmol x min -1 x g liver -1 , and a bolus of [ 3 H]TDC was given to assess metabolism and excretion of bile acids. In CCS livers perfused backward, pericentral cells resembled periportal cells of controls in that time to excrete 50% of administered [ 3 H]-TDC (t 50 ) was reduced by two-thirds and [ 3 H]TDC biotransformation was reduced by about half. In young livers t 50 was half that of adult livers when perfused backward. Biotransformation, however, was not reduced. Young livers biotransformed more than adult controls for any given residence time of bile acid in the liver. They conclude that the difference between pericentral and perioportal cells as regards bile acid processing is adaptive. Livers from young rats biotransform more bile acid than those from controls under similar conditions

Evidence for functional convergence in genes upregulated by herbivores ingesting plant secondary compounds

Science.gov (United States)

2014-01-01

Background Nearly 40 years ago, Freeland and Janzen predicted that liver biotransformation enzymes dictated diet selection by herbivores. Despite decades of research on model species and humans, little is known about the biotransformation mechanisms used by mammalian herbivores to metabolize plant secondary compounds (PSCs). We investigated the independent evolution of PSC biotransformation mechanisms by capitalizing on a dramatic diet change event—the dietary inclusion of creosote bush (Larrea tridentata)—that occurred in the recent evolutionary history of two species of woodrats (Neotoma lepida and N. bryanti). Results By comparing gene expression profiles of two populations of woodrats with evolutionary experience to creosote and one population naïve to creosote, we identified genes either induced by a diet containing creosote PSCs or constitutively higher in populations with evolutionary experience of creosote. Although only one detoxification gene (an aldo-keto reductase) was induced by both experienced populations, these populations converged upon functionally equivalent strategies to biotransform the PSCs of creosote bush by constitutively expressing aldehyde and alcohol dehydrogenases, Cytochromes P450s, methyltransferases, glutathione S-transferases and sulfotransferases. The response of the naïve woodrat population to creosote bush was indicative of extreme physiological stress. Conclusions The hepatic detoxification system of mammals is notoriously complex, with hundreds of known biotransformation enzymes. The comparison herein of woodrat taxa that differ in evolutionary and ecological experience with toxins in creosote bush reveals convergence in the overall strategies used by independent species after a historical shift in diet. In addition, remarkably few genes seemed to be important in this dietary shift. The research lays the requisite groundwork for future studies of specific biotransformation pathways used by woodrats to metabolize the

New cryptotanshinone derivatives with anti-influenza A virus activities obtained via biotransformation by Mucor rouxii.

Science.gov (United States)

He, Wenni; Li, Yao; Qin, Yuejie; Tong, Xiaomei; Song, Zhijun; Zhao, Yu; Wei, Ran; Li, Li; Dai, Huanqin; Wang, Wenzhao; Luo, Houwei; Ye, Xin; Zhang, Lixin; Liu, Xueting

2017-08-01

This paper provides an efficient platform to diversify the structure and pharmaceutical potentials of known natural products. Seven metabolites were obtained via the biotransformation of cryptotanshinone by the fungus Mucor rouxii AS 3.3447, and assigned as 13R-14R-hydroxy-anhydride of 16R-cryptotanshinone (1), 1S-hydroxy-anhydride of 16R-cryptotanshinone (2), 1R-hydroxy-anhydride of 16R-cryptotanshinone (3), 3S-hydroxy-epicryptoacetalide (4), 3S-hydroxy-cryptoacetalide (5), epicryptoacetalide (6), and cryptoacetalide (7). Among these compounds, 1-5 are novel. The ortho-naphthoquinone chromophore of cryptotanshinone was degraded and rearranged by M. rouxii. 1 and 3 showed good anti-influenza A virus activities with the reduced cytotoxic activities compared to the parent substrate cryptotanshinone (8). The structures of all the new compounds were determined on the basis of HRESIMS (high-resolution electrospray ionization mass spectroscopy) spectrometry, NMR (nuclear magnetic resonance) spectroscopy, ECD (electronic circular dichroism) calculations, and the CD (circular dichroism) of "in situ" method with [Rh 2 (OCOCF 3 ) 4 ].

Biotransformation of the polycyclic aromatic hydrocarbon pyrene by the marine polychaete Nereis virens

DEFF Research Database (Denmark)

Jørgensen, Anne; Giessing, Anders M. B.; Rasmussen, Lene Juel

2005-01-01

In vivo and in vitro biotransformation of the polycyclic aromatic hydrocarbon (PAH) pyrene was investigated in the marine polychaete Nereis virens. Assays were designed to characterize phase I and II enzymes isolated from gut tissue. High-pressure liquid chromatography measurement of 1-hydroxypyr......In vivo and in vitro biotransformation of the polycyclic aromatic hydrocarbon (PAH) pyrene was investigated in the marine polychaete Nereis virens. Assays were designed to characterize phase I and II enzymes isolated from gut tissue. High-pressure liquid chromatography measurement of 1...

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta

International Nuclear Information System (INIS)

Brien, J.F.; McLaughlin, B.E.; Breedon, T.H.; Bennett, B.M.; Nakatsu, K.; Marks, G.S.

1986-01-01

This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM [ 14 C]GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentration was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM [ 14 C]GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN-tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABST

Influence of Aroclor 1242 Concentration on Polychlorinated Biphenyl Biotransformations in Hudson River Test Tube Microcosms

Science.gov (United States)

Fish, K. M.

1996-01-01

When 93.3 to 933 (mu)mol of Aroclor 1242 per kg was added to Hudson River sediment test tube microcosms, the rates of polychlorinated biphenyl biotransformations increased with increasing Aroclor 1242 concentration after a 4- to 8-week acclimation period. In contrast, when 37.3 (mu)mol of Aroclor 1242 per kg was added, polychlorinated biphenyl biotransformations occurred at slow constant rates. PMID:16535387

Sustainable production of valuable compound 3-succinoyl-pyridine by genetically engineering Pseudomonas putida using the tobacco waste.

Science.gov (United States)

Wang, Weiwei; Xu, Ping; Tang, Hongzhi

2015-11-17

Treatment of solid and liquid tobacco wastes with high nicotine content remains a longstanding challenge. Here, we explored an environmentally friendly approach to replace tobacco waste disposal with resource recovery by genetically engineering Pseudomonas putida. The biosynthesis of 3-succinoyl-pyridine (SP), a precursor in the production of hypotensive agents, from the tobacco waste was developed using whole cells of the engineered Pseudomonas strain, S16dspm. Under optimal conditions in fed-batch biotransformation, the final concentrations of product SP reached 9.8 g/L and 8.9 g/L from aqueous nicotine solution and crude suspension of the tobacco waste, respectively. In addition, the crystal compound SP produced from aqueous nicotine of the tobacco waste in batch biotransformation was of high purity and its isolation yield on nicotine was 54.2%. This study shows a promising route for processing environmental wastes as raw materials in order to produce valuable compounds.

The impact of different proportions of a treated effluent on the biotransformation of selected micro-contaminants in river water microcosms.

Science.gov (United States)

Nödler, Karsten; Tsakiri, Maria; Licha, Tobias

2014-10-10

Attenuation of micro-contaminants is a very complex field in environmental science and evidence suggests that biodegradation rates of micro-contaminants in the aqueous environment depend on the water matrix. The focus of the study presented here is the systematic comparison of biotransformation rates of caffeine, carbamazepine, metoprolol, paracetamol and valsartan in river water microcosms spiked with different proportions of treated effluent (0%, 0.1%, 1%, and 10%). Biotransformation was identified as the dominating attenuation process by the evolution of biotransformation products such as atenolol acid and valsartan acid. Significantly decreasing biotransformation rates of metoprolol were observed at treated effluent proportions ≥ 0.1% whereas significantly increasing biotransformation rates of caffeine and valsartan were observed in the presence of 10% treated effluent. Potential reasons for the observations are discussed and the addition of adapted microorganisms via the treated effluent was suggested as the most probable reason. The impact of additional phosphorus on the biodegradation rates was tested and the experiments revealed that phosphorus-limitation was not responsible.

Unveiling the biotransformation mechanism of indole in a Cupriavidus sp. strain.

Science.gov (United States)

Qu, Yuanyuan; Ma, Qiao; Liu, Ziyan; Wang, Weiwei; Tang, Hongzhi; Zhou, Jiti; Xu, Ping

2017-12-01

Indole, an important signaling molecule as well as a typical N-heterocyclic aromatic pollutant, is widespread in nature. However, the biotransformation mechanisms of indole are still poorly studied. Here, we sought to unlock the genetic determinants of indole biotransformation in strain Cupriavidus sp. SHE based on genomics, proteomics and functional studies. A total of 177 proteins were notably altered (118 up- and 59 downregulated) in cells grown in indole mineral salt medium when compared with that in sodium citrate medium. RT-qPCR and gene knockout assays demonstrated that an indole oxygenase gene cluster was responsible for the indole upstream metabolism. A functional indole oxygenase, termed IndA, was identified in the cluster, and its catalytic efficiency was higher than those of previously reported indole oxidation enzymes. Furthermore, the indole downstream metabolism was found to proceed via the atypical CoA-thioester pathway rather than conventional gentisate and salicylate pathways. This unusual pathway was catalyzed by a conserved 2-aminobenzoyl-CoA gene cluster, among which the 2-aminobenzoyl-CoA ligase initiated anthranilate transformation. This study unveils the genetic determinants of indole biotransformation and will provide new insights into our understanding of indole biodegradation in natural environments and its functional studies. © 2017 John Wiley & Sons Ltd.

Biotransformation of limonene by bacteria, fungi, yeasts, and plants

NARCIS (Netherlands)

Duetz, W.A.; Bouwmeester, H.J.; Beilen, J.B.; Witholt, B.

2003-01-01

The past 5 years have seen significant progress in the field of limonene biotransformation, especially with regard to the regiospecificity of microbial biocatalysts. Whereas earlier only regiospecific biocatalysts for the 1,2 position (limonene-1,2-diol) and the 8-position (¿±-terpineol) were

Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf)

International Nuclear Information System (INIS)

Schuster, Paul; Bertermann, Ruediger; Snow, Timothy A.; Han Xing; Rusch, George M.; Jepson, Gary W.; Dekant, Wolfgang

2008-01-01

2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a non-ozone-depleting fluorocarbon replacement with a low global warming potential which has been developed as refrigerant. The biotransformation of HFO-1234yf was investigated after inhalation exposure. Male Sprague-Dawley rats were exposed to air containing 2000, 10,000, or 50,000 ppm HFO-1234yf for 6 h and male B6C3F1 mice were exposed to 50,000 ppm HFO-1234yf for 3.5 h in a dynamic exposure chamber (n = 5/concentration). After the end of the exposure, animals were individually housed in metabolic cages and urines were collected at 6 or 12-hour intervals for 48 h. For metabolite identification, urine samples were analyzed by 1 H-coupled and decoupled 19 F-NMR and by LC/MS-MS or GC/MS. Metabolites were identified by 19 F-NMR chemical shifts, signal multiplicity, 1 H- 19 F coupling constants and by comparison with synthetic reference compounds. In all urine samples, the predominant metabolites were two diastereomers of N-acetyl-S-(3,3,3-trifluoro-2-hydroxy-propyl)-L-cysteine. In 19 F-NMR, the signal intensity of these metabolites represented more than 85% (50,000 ppm) of total 19 F related signals in the urine samples. Trifluoroacetic acid, 3,3,3-trifluorolactic acid, 3,3,3-trifluoro-1-hydroxyacetone, 3,3,3-trifluoroacetone and 3,3,3-trifluoro-1,2-dihydroxypropane were present as minor metabolites. Quantification of N-acetyl-S-(3,3,3-trifluoro-2-hydroxy-propyl)-L-cysteine by LC/MS-MS showed that most of this metabolite (90%) was excreted within 18 h after the end of exposure (t 1/2 app. 6 h). In rats, the recovery of N-acetyl-S-(3,3,3-trifluoro-2-hydroxy-propyl)-L-cysteine excreted within 48 h in urine was determined as 0.30 ± 0.03, 0.63 ± 0.16, and 2.43 ± 0.86 μmol at 2000, 10,000 and 50,000 ppm, respectively suggesting only a low extent (<< 1% of dose received) of biotransformation of HFO-1234yf. In mice, the recovery of this metabolite was 1.774 ± 0.4 μmol. Metabolites identified after in vitro incubations of HFO

Immobilization of biogenic Pd(0) in anaerobic granular sludge for the biotransformation of recalcitrant halogenated pollutants in UASB reactors.

Science.gov (United States)

Pat-Espadas, Aurora M; Razo-Flores, Elías; Rangel-Mendez, J Rene; Ascacio-Valdes, Juan A; Aguilar, Cristobal N; Cervantes, Francisco J

2015-10-19

The capacity of anaerobic granular sludge to reduce Pd(II), using ethanol as electron donor, in an upflow anaerobic sludge blanket (UASB) reactor was demonstrated. Results confirmed complete reduction of Pd(II) and immobilization as Pd(0) in the granular sludge. The Pd-enriched sludge was further evaluated regarding biotransformation of two recalcitrant halogenated pollutants: 3-chloro-nitrobenzene (3-CNB) and iopromide (IOP) in batch and continuous operation in UASB reactors. The superior removal capacity of the Pd-enriched biomass when compared with the control (not exposed to Pd) was demonstrated in both cases. Results revealed 80 % of IOP removal efficiency after 100 h of incubation in batch experiments performed with Pd-enriched biomass whereas only 28 % of removal efficiency was achieved in incubations with biomass lacking Pd. The UASB reactor operated with the Pd-enriched biomass achieved 81 ± 9.5 % removal efficiency of IOP and only 61 ± 8.3 % occurred in the control reactor lacking Pd. Regarding 3-CNB, it was demonstrated that biogenic Pd(0) promoted both nitro-reduction and dehalogenation resulting in the complete conversion of 3-CNB to aniline while in the control experiment only nitro-reduction was documented. The complete biotransformation pathway of both contaminants was proposed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis evidencing a higher degree of nitro-reduction and dehalogenation of both contaminants in the experiments with Pd-enriched anaerobic sludge as compared with the control. A biotechnological process is proposed to recover Pd(II) from industrial streams and to immobilize it in anaerobic granular sludge. The Pd-enriched biomass is also proposed as a biocatalyst to achieve the biotransformation of recalcitrant compounds in UASB reactors.

Effect of cystamine on postirradiation changes in action and biotransformation of hexobarbital (Narcosan)

International Nuclear Information System (INIS)

Wojciak, Z.; Kozaryn, I.; Szczawinska, K.; Ratka, A.

1985-01-01

The influence of cystamine (100 mg/kg i.p.) on hypnotic potency and biotransformation of hexobarbital (180 mg/kg i.p.) in irradiated rats was examined. Cystamine used as a radioprotector shortend duration of hexobarbital-induced sleep, which is prolonged during radiation sickness. Although in normal rats cystamine has no effect on the activity of hexobarbital oxidase and hexobarbital biotransformation, higher activity of the enzyme and increased elimination of hexobarbital metabolites after cystamine were observed in irradiated rats. Such results confirmed radioprotective action of cystamine. 26 refs., 2 figs., 3 tabs. (author)

Identification of bottlenecks for P450 biotransformation processes

DEFF Research Database (Denmark)

Andersson, Marie Therese; Törnvall, Ulrika; Tufvesson, Pär

Cytochrome P450 monooxygenases (P450 or CYP) is a group of heme-containing enzymes hydroxylating non-activated hydrocarbons in a stereospecific manner, something that is hard to achieve via classical chemistry. The importance of these reactions can be stressed by the hydroxylation of steroids, bu...... biotransformation process identifying the limiting parameters and defining relevant targets....

Indolealkylamines: Biotransformations and Potential Drug–Drug Interactions

OpenAIRE

Yu, Ai-Ming

2008-01-01

Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug–drug interactions (DDIs). A stable, principal metabolite of an IAA drug of ab...

Biotransformation of furanocoumarins by Cunninghamella elegans

Directory of Open Access Journals (Sweden)

Ghada Ismail El-shahat Ali Attia

2015-06-01

Full Text Available Biotransformation of Furanocoumarins; psoralen (1, bergapten (2, xanthotoxin (3 and imperatorin (4 was explored by Cunninghamella elegans NRRL 1392, revealing the metabolism of psoralen (1 and bergapten (2 into bergaptol (5, while xanthotoxin (3 and imperatorin (4 were converted into xanthotoxol (6. On the other hand unexpected conversion of xanthotoxin (3 into 3,4 dihydroxanthotoxin (7 occurred. The structure of the isolated pure metabolites was established using physical and spectroscopic techniques including, melting points, IR, 1H NMR, 13C NMR and mass spectroscopy.

[THE SYSTEM OF XENOBIOTICS BIOTRANSFORMATION OF HELMINTHS. RESEMBLANCE AND DIFFERENSES FROM SIMILAR HOST SYSTEMS (REWEW)].

Science.gov (United States)

Smirnov, L P; Borvinskaya, E V; Suhovskaya, I V

2016-01-01

The three phases system xenobiotic biotransformation in cells as prokaryotes as eukaryotes was formed during the process of evolution. Clear and managed function of all three links of this system guarantee the survival of living organisms at alteration of chemical component of environment. Oxidation, reduction or hydrolysis of xenobiotics realize in phase I by insertion or opening reactive and hydrophilic groups in structure of drug molecule. In phase II xenobiotics or their metabolites from phase I conjugate with endogenic compounds, main of there are glutathione, glucuronic acid, amino acids and sulphates. Active transport of substrata, metabolites and conjugates through cell lipid membranes special transport proteins carry out (phase III). The system of xenobiotics biotransformation of helminths has essential differences from the same of vertebrate hosts. In particular, parasites do not reveal the activity of prime oxidases of phase I, such as CYP or FMO, in spite of the genes of these enzymes in DNA. As this phenomenon displays mainly in adult helminths, living in guts of vertebrates, then the hypothesis was formulated that this effect is related with adaptation to conditions of strong deficiency of oxygen, arise in a process of evolution (Kotze et al., 2006). Literature data testify the existence in helminths of unique forms of enzymes of phase II, the investigation of which present doubtless interest in relation with possible role in adaptation to parasitic mode of life. Notwithstanding that many of helminths GST in greater or lesser degree similar with enzymes of M, P, S and О classes of other organisms, nevertheless they have essential structural differences as compared with enzymes of hosts that makes perspective the search of specific anthelminthics vaccines. Transport of xenobiotics is now considered phase III of biotransformation. It was shown that proteins of this phase (ATP binding cassette transporters (ABC ) of parasites) play a key role in efflux

A biotransformation process for the production of cucurbitacin B from its glycoside using a selected Streptomyces sp.

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Mei, Jianfeng; Li, Sha; Jin, Hang; Tang, Lan; Yi, Yu; Wang, Hong; Ying, Guoqing

2016-09-01

Cucurbitacin B (CuB) and its glycoside, cucurbitacin B 2-o-β-D-glucoside (CuBg), abundantly occur in the pedicels of Cucumis melo. Compared with CuB, CuBg is not efficiently extracted from the pedicels. Furthermore, the anticancer activity of CuBg is lower than that of the aglycone. A process for CuBg biotransformation to CuB was developed for the first time. A strain of Streptomyces species that converts CuBg into CuB was isolated from an enrichment culture of C. melo pedicels. After optimization of conditions for enzyme production and biotransformation, a maximum conversion rate of 92.6 % was obtained at a CuBg concentration of 0.25 g/L. When biotransformation was performed on C. melo pedicel extracts, the CuB concentration in the extracts increased from 1.50 to 3.27 g/L. The conversion rate was almost 100 %. The developed process may be an effective biotransformation method for industrial production CuB from C. melo pedicels for pharmaceuticals.

The Extracts and Major Compounds Derived from Astragali Radix Alter Mitochondrial Bioenergetics in Cultured Cardiomyocytes: Comparison of Various Polar Solvents and Compounds

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Yun Huang

2018-05-01

Full Text Available Astragali Radix (AR is a widely used “Qi-invigorating” herb in China for its tonic effects in strengthening biological tissues. The extract of AR contains abundant antioxidants, including astragalosides and isoflavonoids. However, very few reports have systematically measured the effects of the major components of AR on cell mitochondrial bioenergetics. Here, a systemic approach employing an extracellular flux analyzer was developed to evaluate mitochondrial respiration in cultured cardiomyocyte cells H9C2. The effects of different polar extractives, as well as of the major compounds of AR, were compared. The contents of astragaloside IV, calycosin, formononetin, and genistein in the AR extracts obtained by using water, 50% ethanol, and 90% ethanol were measured by liquid chromatograph-mass spectrometer (LC–MS. The antioxidant activities of the AR extracts, as well as of their major compounds, were determined by measuring the free radical scavenging activity and protective effects in tert-butyl hydroperoxide (tBHP-treated H9C2 cells. By monitoring the real-time oxygen consumption rate (OCR in tBHP-treated cardiomyocytes with a Seahorse extracellular flux analyzer, the tonic effects of the AR extracts and of their main compounds on mitochondrial bioenergetics were evaluated. AR water extracts possessed the strongest antioxidant activity and protective effects in cardiomyocytes exposed to oxidative stress. The protection was proposed to be mediated via increasing the spare respiratory capacity and mitochondrial ATP production in the stressed cells. The major compounds of AR, astragaloside IV and genistein, showed opposite effects in regulating mitochondrial bioenergetics. These results demonstrate that highly polar extracts of AR, especially astragaloside-enriched extracts, possess better tonic effects on mitochondrial bioenergetics of cultured cardiomyocytes than extracts with a lower polarity.

Optimization of Malaxation Process using Major Aroma Compounds in Virgin Olive Oil

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Serife Cevik

Full Text Available ABSTRACT Optimization of major aroma compounds in olive oils produced from fruits at three maturity stages wasstudied. A central composite design was used for the optimization of malaxation conditions of temperature and times, each at five levels with 13 runs including five central points. The responses of interest were trans-2-hexenal and hexanal, which were investigated and their contents were optimized. A full quadratic second order regression model including the linear, quadratic, and two factor interaction effects was proposed to explain the variation in the contents of target compounds depending on the malaxation conditions. Adequacies of models were evaluated by checking regression coefficients for each model. Models were found to work with high success for trans-2-hexenal prediction for oils from fruits at both purple and black stages, whereas the model for hexanalwas only in black stage oil. Their regression coefficients were higher than 0.86. Influences of time and temperature for the malaxation process were found to be significant for the transition of major aroma compounds from the fruit matrix to olive oil. The optimum conditions of temperature and time pairs to maximize trans-2-hexenal and hexanal was found to be 23°C/31 minutes for black olive and to maximize only trans-2-hexenal was also 29°C/41 minutes for purple olive.

Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria

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Ma Miao

2010-04-01

Full Text Available Abstract Background The effects of enterolignans, e.g., enterodiol (END and particularly its oxidation product, enterolactone (ENL, on prevention of hormone-dependent diseases, such as osteoporosis, cardiovascular diseases, hyperlipemia, breast cancer, colon cancer, prostate cancer and menopausal syndrome, have attracted much attention. To date, the main way to obtain END and ENL is chemical synthesis, which is expensive and inevitably leads to environmental pollution. To explore a more economic and eco-friendly production method, we explored biotransformation of enterolignans from precursors contained in defatted flaxseeds by human intestinal bacteria. Results We cultured fecal specimens from healthy young adults in media containing defatted flaxseeds and detected END from the culture supernatant. Following selection through successive subcultures of the fecal microbiota with defatted flaxseeds as the only carbon source, we obtained a bacterial consortium, designated as END-49, which contained the smallest number of bacterial types still capable of metabolizing defatted flaxseeds to produce END. Based on analysis with pulsed field gel electrophoresis, END-49 was found to consist of five genomically distinct bacterial lineages, designated Group I-V, with Group I strains dominating the culture. None of the individual Group I-V strains produced END, demonstrating that the biotransformation of substrates in defatted flaxseeds into END is a joint work by different members of the END-49 bacterial consortium. Interestingly, Group I strains produced secoisolariciresinol, an important intermediate of END production; 16S rRNA analysis of one Group I strain established its close relatedness with Klebsiella. Genomic analysis is under way to identify all members in END-49 involved in the biotransformation and the actual pathway leading to END-production. Conclusion Biotransformation is a very economic, efficient and environmentally friendly way of mass

Monitoring biodegradation of ethene and bioremediation of chlorinated ethenes at a contaminated site using compound-specific isotope analysis (CSIA).

Science.gov (United States)

Mundle, Scott O C; Johnson, Tiffany; Lacrampe-Couloume, Georges; Pérez-de-Mora, Alfredo; Duhamel, Melanie; Edwards, Elizabeth A; McMaster, Michaye L; Cox, Evan; Révész, Kinga; Sherwood Lollar, Barbara

2012-02-07

Chlorinated ethenes are commonly found in contaminated groundwater. Remediation strategies focus on transformation processes that will ultimately lead to nontoxic products. A major concern with these strategies is the possibility of incomplete dechlorination and accumulation of toxic daughter products (cis-1,2-dichloroethene (cDCE), vinyl chloride (VC)). Ethene mass balance can be used as a direct indicator to assess the effectiveness of dechlorination. However, the microbial processes that affect ethene are not well characterized and poor mass balance may reflect biotransformation of ethene rather than incomplete dechlorination. Microbial degradation of ethene is commonly observed in aerobic systems but fewer cases have been reported in anaerobic systems. Limited information is available on the isotope enrichment factors associated with these processes. Using compound-specific isotope analysis (CSIA) we determined the enrichment factors associated with microbial degradation of ethene in anaerobic microcosms (ε = -6.7‰ ± 0.4‰, and -4.0‰ ± 0.8‰) from cultures collected from the Twin Lakes wetland area at the Savannah River site in Georgia (United States), and in aerobic microcosms (ε = -3.0‰ ± 0.3‰) from Mycobacterium sp. strain JS60. Under anaerobic and aerobic conditions, CSIA can be used to determine whether biotransformation of ethene is occurring in addition to biodegradation of the chlorinated ethenes. Using δ(13)C values determined for ethene and for chlorinated ethenes at a contaminated field site undergoing bioremediation, this study demonstrates how CSIA of ethene can be used to reduce uncertainty and risk at a site by distinguishing between actual mass balance deficits during reductive dechlorination and apparent lack of mass balance that is related to biotransformation of ethene.

Single step biotransformation of corn oil phytosterols to boldenone by a newly isolated Pseudomonas aeruginosa

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Mohamed Eisa

2016-09-01

Full Text Available A new potent Pseudomonas aeruginosa isolate capable for biotransformation of corn oil phytosterol (PS to 4-androstene-3, 17-dione (AD, testosterone (T and boldenone (BOL was identified by phenotypic analysis and 16S rRNA gene sequencing. Sequential statistical strategy was used to optimize the biotransformation process mainly concerning BOL using Factorial design and response surface methodology (RSM. The production of BOL in single step microbial biotransformation from corn oil phytosterols by P. aeruginosa was not previously reported. Results showed that the pH concentration of the medium, (NH42SO4 and KH2PO4 were the most significant factors affecting BOL production. By analyzing the statistical model of three-dimensional surface plot, BOL production increased from 36.8% to 42.4% after the first step of optimization, and the overall biotransformation increased to 51.9%. After applying the second step of the sequential statistical strategy BOL production increased to 53.6%, and the overall biotransformation increased to 91.9% using the following optimized medium composition (g/l distilled water (NH42SO4, 2; KH2PO4, 4; Na2HPO4. 1; MgSO4·7H2O, 0.3; NaCl, 0.1; CaCl2·2H2O, 0.1; FeSO4·7H2O, 0.001; ammonium acetate 0.001; Tween 80, 0.05%; corn oil 0.5%; 8-hydroxyquinoline 0.016; pH 8; 200 rpm agitation speed and incubation time 36 h at 30 °C. Validation experiments proved the adequacy and accuracy of model, and the results showed the predicted value agreed well with the experimental values.

Physiologically based modeling of hepatic and gastrointestinal biotransformation in fish

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In fish, as in mammals, the liver generally viewed as the principal site of chemical biotransformation. For waterborne exposures, such as those conducted in support of standardized BCF testing, the effects of hepatic metabolism on chemical accumulation can be simulated using rela...

Toxicity, Bioaccumulation and Biotransformation of Silver Nanoparticles in Marine Organisms

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The toxicity, bioaccumulation and biotransformation of citrate and polyvinylpyrrolidone (PVP) capped silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) and titanium dioxide (TiO2) NPs in marine organisms via marine sediment exposure were investigated. Results from 7-d sedimen...

Transformation of saturated nitrogen-containing heterocyclic compounds by microorganisms.

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Parshikov, Igor A; Silva, Eliane O; Furtado, Niege A J C

2014-02-01

The saturated nitrogen-containing heterocyclic compounds include many drugs and compounds that may be used as synthons for the synthesis of other pharmacologically active substances. The need for new derivatives of saturated nitrogen-containing heterocycles for organic synthesis, biotechnology and the pharmaceutical industry, including optically active derivatives, has increased interest in microbial synthesis. This review provides an overview of microbial technologies that can be valuable to produce new derivatives of saturated nitrogen-containing heterocycles, including hydroxylated derivatives. The chemo-, regio- and enantioselectivity of microbial processes can be indispensable for the synthesis of new compounds. Microbial processes carried out with fungi, including Beauveria bassiana, Cunninghamella verticillata, Penicillium simplicissimum, Aspergillus niger and Saccharomyces cerevisiae, and bacteria, including Pseudomonas sp., Sphingomonas sp. and Rhodococcus erythropolis, biotransform many substrates efficiently. Among the biological activities of saturated nitrogen-containing heterocyclic compounds are antimicrobial, antitumor, antihypertensive and anti-HIV activities; some derivatives are effective for the treatment and prevention of malaria and trypanosomiasis, and others are potent glycosidase inhibitors.

Identificationof Major Phenolic Compounds of Chinese Water Chestnut and their Antioxidant Activity

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Yueming Jiang

2007-04-01

Full Text Available Chinese water chestnut (CWC is one of the most popular foods among Asian people due to its special taste and medical function. Experiments were conducted to test the antioxidant activity and then determine the major phenolic compound components present in CWC. CWC phenolic extract strongly inhibited linoleic acid oxidation and exhibited a dose-dependent free-radical scavenging activity against α,α-diphenyl-β-picrylhydrazyl (DPPH radicals, superoxide anions and hydroxyl radicals, which was superior to ascorbic acid and butylated hydroxytoluene (BHT, two commercial used antioxidants. Furthermore, the CWC extract was found to have a relatively higher reducing power, compared with BHT. The major phenolic compounds present in CWC tissues were extracted, purified and identified by high-performance liquid chromatograph (HPLC as (–-gallocatechin gallate, (–-epicatechin gallate and (+-catechin gallate. This study suggests that CWC tissues exhibit great potential for antioxidant activity and may be useful for their nutritional and medicinal functions.

Critical Evaluation of a Human In Vitro Biotransformation Rate Database

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Chemical biotransformation is critical information in the understanding of how a chemical may elicit health effects in humans or in the environment. Despite the fundamental value of these data, very relatively few measured in vivo data are available for humans compared to the tho...

Biotransformation of glyceryl trinitrate (GTN) in isolated bovine pulmonary artery (BPA) and bovine pulmonary vein (BPV)

International Nuclear Information System (INIS)

Anon.

1986-01-01

A proposed mechanism of GTN-induced vasodilation requires biotransformation of GTN to glyceryl dinitrate (GDN). They have previously shown that GTN is metabolized to GDN during relaxation of isolated rabbit aorta. The authors have extended this study to include BPA and BPV and to determine if their sensitivity to GTN correlates with their ability to metabolize GTN. Strips of BPA and BPV were contracted submaximally with KCl and then incubated with 0.5 μM 14 C-GTN for 2 min. GTN-induced relaxation of these vessels was monitored and tissue GTN and metabolite concentrations were measured. Data are presented which support the above hypothesis that GTN biotransformation and relaxation occur together in vascular smooth muscle; however, there appear to be factors other than extent of GTN biotransformation that account for the difference in sensitivity to GTN of the artery and vein

Disposition and biotransformation of the acetylenic retinoid tazarotene in humans.

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Attar, Mayssa; Yu, Dale; Ni, Jinsong; Yu, Zhiling; Ling, Kah-Hiing John; Tang-Liu, Diane D-S

2005-10-01

Oral tazarotene, an acetylenic retinoid, is in clinical development for the treatment of psoriasis. The disposition and biotransformation of tazarotene were investigated in six healthy male volunteers, following a single oral administration of a 6 mg (100 microCi) dose of [14C]tazarotene, in a gelatin capsule. Blood levels of radioactivity peaked 2 h postdose and then rapidly declined. Total recovery of radioactivity was 89.2+/-8.0% of the administered dose, with 26.1+/-4.2% in urine and 63.0+/-7.0% in feces, within 7 days of dosing. Only tazarotenic acid, the principle active metabolite formed via esterase hydrolysis of tazarotene, was detected in blood. One major urinary oxidative metabolite, tazarotenic acid sulfoxide, accounted for 19.2+/-3.0% of the dose. The majority of radioactivity recovered in the feces was attributed to tazarotenic acid representing 46.9+/-9.9% of the dose and only 5.82+/-3.84% of dose was excreted as unchanged tazarotene. Thus following oral administration, tazarotene was rapidly absorbed and underwent extensive hydrolysis to tazarotenic acid, the major circulating species in the blood that was then excreted unchanged in feces. A smaller fraction of tazarotenic acid was further metabolized to an inactive sulfoxide that was excreted in the urine. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and their major contributed antioxidant compounds

OpenAIRE

Mao, Shuqin; Wang, Kaidi; Lei, Yukun; Yao, Shuting; Lu, Baiyi; Huang, Weisu

2017-01-01

The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea were evaluated, and their major antioxidant compounds contributed to the total amount of synergy were determined. The antioxidant compounds in O. fragrans flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The synergistic antioxidant interactions between O. fragrans flowers with green tea and their antioxidant compounds were tested using the Prieto?s model after the simulated digestion. T...

Mixed function oxidase dependent biotransformation of polychlorinated biphenyls by different species of fish from the North Sea

DEFF Research Database (Denmark)

Mehrtens, G.; Laturnus, F.

1999-01-01

Mixed function oxidase (MFO) dependent biotransformation of polychlorinated biphenyls (PCBs) was measured in three different fish species from the North Sea. Liver microsomes of plaice (Pleuronectes platessa), dab (Limanda limanda) and cod (Gadus morhua) were isolated and incubated with different....... Biotransformations were also species dependent. The flatfish dab and plaice exhibited higher metabolic rates than cod (C) 1999 Elsevier Science Ltd. All rights reserved....

Biotransformation and Rearrangement of Laromustine.

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Nassar, Alaa-Eldin F; Wisnewski, Adam V; King, Ivan

2016-08-01

This review highlights the recent research into the biotransformations and rearrangement of the sulfonylhydrazine-alkylating agent laromustine. Incubation of [(14)C]laromustine with rat, dog, monkey, and human liver microsomes produced eight radioactive components (C-1 to C-8). There was little difference in the metabolite profile among the species examined, partly because NADPH was not required for the formation of most components, which instead involved decomposition and/or hydrolysis. The exception was C-7, a hydroxylated metabolite, largely formed by CYP2B6 and CYP3A4/5. Liquid chromatography-multistage mass spectrometry (LC-MS(n)) studies determined that collision-induced dissociation, and not biotransformation or enzyme catalysis, produced the unique mass spectral rearrangement. Accurate mass measurements performed with a Fourier-transform ion cyclotron resonance mass spectrometer (FTICR-MS) significantly aided determination of the elemental compositions of the fragments and in the case of laromustine revealed the possibility of rearrangement. Further, collision-induced dissociation produced the loss of nitrogen (N2) and methylsulfonyl and methyl isocyanate moieties. The rearrangement, metabolite/decomposition products, and conjugation reactions were analyzed utilizing hydrogen-deuterium exchange, exact mass, (13)C-labeled laromustine, nuclear magnetic resonance spectroscopy (NMR), and LC-MS(n) experiments to assist with the assignments of these fragments and possible mechanistic rearrangement. Such techniques produced valuable insights into these functions: 1) Cytochrome P450 is involved in C-7 formation but plays little or no role in the conversion of [(14)C]laromustine to C-1 through C-6 and C-8; 2) the relative abundance of individual degradation/metabolite products was not species-dependent; and 3) laromustine produces several reactive intermediates that may produce the toxicities seen in the clinical trials. Copyright © 2016 by The American Society for

Microbial transformation of citral by Penicillium sp..

Science.gov (United States)

Esmaeili, Akbar; Tavassoli, Afsaneh

2010-01-01

Thymol is present in the essential oils from herbs and spices, such as thyme. It is produced by these plant species as a chemical defense against phytopathogenic microorganisms. Therefore, this compound has attracted great attention in food industry, i.e., it has been used as a natural preservative in foods such as cheese to prevent fungal growth. Previous studies concerning the biotransformation of nerol by Penicillium sp. and microbial transformation of citral by sporulated surface cultures method (SSCM) of Penicillium digitatum have been reported. The objective of this research was to study the pathway involved during biotransformation of citral by Penicillium sp. using two methods. The culture preparation was done using different microbial methods and incubation periods to obtain Penicillium for citral biotransformation. The biotransformation products were identified by gas chromatography (GC) and gas chromatography/mass spectroscopy (GC/MS). A comparison of the two methods showed that SSCM was more effective, its major products were thymol (21.5 %), geranial (18.6 %) and nerol (13.7 %). LM produced only one compound — thymol — with a low efficiency.

In vitro to in vivo extrapolation of biotransformation rates for assessing bioaccumulation of hydrophobic organic chemicals in mammals.

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Lee, Yung-Shan; Lo, Justin C; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2017-07-01

Incorporating biotransformation in bioaccumulation assessments of hydrophobic chemicals in both aquatic and terrestrial organisms in a simple, rapid, and cost-effective manner is urgently needed to improve bioaccumulation assessments of potentially bioaccumulative substances. One approach to estimate whole-animal biotransformation rate constants is to combine in vitro measurements of hepatic biotransformation kinetics with in vitro to in vivo extrapolation (IVIVE) and bioaccumulation modeling. An established IVIVE modeling approach exists for pharmaceuticals (referred to in the present study as IVIVE-Ph) and has recently been adapted for chemical bioaccumulation assessments in fish. The present study proposes and tests an alternative IVIVE-B technique to support bioaccumulation assessment of hydrophobic chemicals with a log octanol-water partition coefficient (K OW ) ≥ 4 in mammals. The IVIVE-B approach requires fewer physiological and physiochemical parameters than the IVIVE-Ph approach and does not involve interconversions between clearance and rate constants in the extrapolation. Using in vitro depletion rates, the results show that the IVIVE-B and IVIVE-Ph models yield similar estimates of rat whole-organism biotransformation rate constants for hypothetical chemicals with log K OW  ≥ 4. The IVIVE-B approach generated in vivo biotransformation rate constants and biomagnification factors (BMFs) for benzo[a]pyrene that are within the range of empirical observations. The proposed IVIVE-B technique may be a useful tool for assessing BMFs of hydrophobic organic chemicals in mammals. Environ Toxicol Chem 2017;36:1934-1946. © 2016 SETAC. © 2016 SETAC.

BIOACCUMULATION AND ENANTIOSELECTIVE BIOTRANSFORMATION OF FIPRONIL BY RAINBOW TROUT (ONCORHYNCHUS MYKISS)

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Dietary accumulation and enantioselective biotransformation was determined for rainbow trout (Oncorhynchus mykiss) exposed to fipronil, a widely used chiral pesticide. Measurement of the fish carcass tissue (whole fish minus GI tract and liver) showed a rapid accumulation of fip...

Biotransformation of the Mycotoxin Deoxynivalenol in Fusarium Resistant and Susceptible Near Isogenic Wheat Lines

Science.gov (United States)

Kluger, Bernhard; Bueschl, Christoph; Lemmens, Marc; Michlmayr, Herbert; Malachova, Alexandra; Koutnik, Andrea; Maloku, Imer; Berthiller, Franz; Adam, Gerhard; Krska, Rudolf; Schuhmacher, Rainer

2015-01-01

In this study, a total of nine different biotransformation products of the Fusarium mycotoxin deoxynivalenol (DON) formed in wheat during detoxification of the toxin are characterized by liquid chromatography—high resolution mass spectrometry (LC-HRMS). The detected metabolites suggest that DON is conjugated to endogenous metabolites via two major metabolism routes, namely 1) glucosylation (DON-3-glucoside, DON-di-hexoside, 15-acetyl-DON-3-glucoside, DON-malonylglucoside) and 2) glutathione conjugation (DON-S-glutathione, “DON-2H”-S-glutathione, DON-S-cysteinyl-glycine and DON-S-cysteine). Furthermore, conjugation of DON to a putative sugar alcohol (hexitol) was found. A molar mass balance for the cultivar ‘Remus’ treated with 1 mg DON revealed that under the test conditions approximately 15% of the added DON were transformed into DON-3-glucoside and another 19% were transformed to the remaining eight biotransformation products or irreversibly bound to the plant matrix. Additionally, metabolite abundance was monitored as a function of time for each DON derivative and was established for six DON treated wheat lines (1 mg/ear) differing in resistance quantitative trait loci (QTL) Fhb1 and/or Qfhs.ifa-5A. All cultivars carrying QTL Fhb1 showed similar metabolism kinetics: Formation of DON-Glc was faster, while DON-GSH production was less efficient compared to cultivars which lacked the resistance QTL Fhb1. Moreover, all wheat lines harboring Fhb1 showed significantly elevated D3G/DON abundance ratios. PMID:25775425

Unexpected Biotransformation of the HDAC Inhibitor Vorinostat Yields Aniline-Containing Fungal Metabolites.

Science.gov (United States)

Adpressa, Donovon A; Stalheim, Kayla J; Proteau, Philip J; Loesgen, Sandra

2017-07-21

The diversity of genetically encoded small molecules produced by filamentous fungi remains largely unexplored, which makes these fungi an attractive source for the discovery of new compounds. However, accessing their full chemical repertoire under common laboratory culture conditions is a challenge. Epigenetic manipulation of gene expression has become a well-established tool for overcoming this obstacle. Here, we report that perturbation of the endophytic ascomycete Chalara sp. 6661, producer of the isofusidienol class of antibiotics, with the HDAC inhibitor vorinostat resulted in the production of four new modified xanthones. The structures of chalanilines A (1) and B (2) and adenosine-coupled xanthones A (3) and B (4) were determined by extensive NMR spectroscopic analyses, and the bioactivities of 1-4 were tested in antibiotic and cytotoxicity assays. Incorporation studies with deuterium-labeled vorinostat indicate that the aniline moiety in chalalanine A is derived from vorinostat itself. Our study shows that Chalara sp. is able to metabolize the HDAC inhibitor vorinostat to release aniline. This is a rare report of fungal biotransformation of the popular epigenetic modifier vorinostat into aniline-containing polyketides.

Effective biotransformation and detoxification of anthraquinone dye reactive blue 4 by using aerobic bacterial granules.

Science.gov (United States)

Chaudhari, Ashvini U; Paul, Dhiraj; Dhotre, Dhiraj; Kodam, Kisan M

2017-10-01

Treatment of textile wastewater containing anthraquinone dye is quite a huge challenge due to its complex aromatic structure and toxicity. Present study deals with the degradation and detoxification of anthraquinone dye reactive blue 4 using aerobic bacterial granules. Bacterial granules effectively decolorized reactive blue 4 at wide range of pH (4.0-11.0) and temperature (20-55 °C) as well as decolorized and tolerated high concentration of reactive blue 4 dye upto 1000 mg l -1 with V max 6.16 ± 0.82 mg l -1 h -1 and K m 227 ± 41 mg l -1 . Metagenomics study evaluates important role of Clostridia, Actinobacteria, and Proteobacterial members in biotransformation and tolerance of high concentrations of reactive blue 4 dye. Up-regulation of xenobiotic degradation and environmental information processing pathways during dye exposure signifies their noteworthy role in dye degradation. Biotransformation of dye was confirmed by significant decrease in the values of total suspended solids, biological and chemical oxygen demand. The metabolites formed after biotransformation was characterized by FT-IR and GC-MS analysis. The reactive blue 4 dye was found to be phytotoxic, cytotoxic and genotoxic whereas its biotransformed product were non-toxic. This study comprehensively illustrates that, bacterial aerobic granules can be used for eco-friendly remediation and detoxification of wastewater containing high organic load of anthraquinone dye. Copyright © 2017 Elsevier Ltd. All rights reserved.

The use of pig hepatocytes for biotransformation and toxicity studies

NARCIS (Netherlands)

Hoogenboom, L.A.P.

1991-01-01

The three main objectives of this study were, (1) to investigate the possibility to isolate viable hepatocytes from liver samples of pigs, (2) to study their use for biotransformation and toxicity studies, and (3) to demonstrate the value of this model, in particular in the field of residue

Production of Two Novel Methoxy-Isoflavones from Biotransformation of 8-Hydroxydaidzein by Recombinant Escherichia coli Expressing O-Methyltransferase SpOMT2884 from Streptomyces peucetius

Science.gov (United States)

Chiang, Chien-Min; Ding, Hsiou-Yu; Tsai, Ya-Ting; Chang, Te-Sheng

2015-01-01

Biotransformation of 8-hydroxydaidzein by recombinant Escherichia coli expressing O-methyltransferase (OMT) SpOMT2884 from Streptomyces peucetius was investigated. Two metabolites were isolated and identified as 7,4′-dihydroxy-8-methoxy-isoflavone (1) and 8,4′-dihydroxy-7-methoxy-isoflavone (2), based on mass, 1H-nuclear magnetic resonance (NMR) and 13C-NMR spectrophotometric analysis. The maximum production yields of compound (1) and (2) in a 5-L fermenter were 9.3 mg/L and 6.0 mg/L, respectively. The two methoxy-isoflavones showed dose-dependent inhibitory effects on melanogenesis in cultured B16 melanoma cells under non-toxic conditions. Among the effects, compound (1) decreased melanogenesis to 63.5% of the control at 25 μM. This is the first report on the 8-O-methylation activity of OMT toward isoflavones. In addition, the present study also first identified compound (1) with potent melanogenesis inhibitory activity. PMID:26610478

Sublethal toxicity and biotransformation of pyrene in Lumbriculus variegatus (Oligochaeta)

International Nuclear Information System (INIS)

Maeenpaeae, K.; Leppaenen, M.T.; Kukkonen, J.V.K.

2009-01-01

The aim of this work was to study the toxicity and biotransformation of polyaromatic hydrocarbon (PAH) pyrene in the oligochaete aquatic worm, Lumbriculus variegatus. PAHs are ubiquitous environmental pollutants that pose a hazard to aquatic organisms, and metabolizing capability is poorly known in the case of many invertebrate species. To study the toxicity and biotransformation of pyrene, the worm was exposed for 15 days to various concentrations of water-borne pyrene. The dorsal blood vessel pulse rate was used as a sublethal endpoint. Pyrene biotransformation by L. variegatus was studied and the critical body residues (CBR) were estimated for pyrene toxicity. The toxicokinetics of pyrene uptake was evaluated. A combination of radiolabeled ( 14 C) and nonlabeled pyrene was used in the exposures, and liquid scintillation counting (LSC) and high-pressure liquid chromatography were employed in both water and tissue residue analyses. The results showed that L. variegatus was moderately able to metabolize pyrene to 1-hydroxypyrene (1-HP), thus demonstrating that the phase-I-like oxidizing enzyme system metabolizes pyrene in L. variegatus. The amount of the 1-HP was 1-2% of the amount of pyrene in the worm tissues. The exposure to pyrene reduced the blood vessel pulse rate significantly (p < 0.05), showing that pyrene had a narcotic effect. The estimated CBRs remained constant during the exposure time, varying from 0.120 to 0.174 mmol pyrene/kg worm wet weight. The bioconcentration factors (BCF) decreased as exposure concentration increased. It was suggested that the increased toxicity of pyrene accounted for the decrease in BCFs by lowering the activity of the organism

The impact of microbial biotransformation of catechin in enhancing the allelopathic effects of Rhododendron formosanum.

Science.gov (United States)

Wang, Chao-Min; Li, Tsai-Chi; Jhan, Yun-Lian; Weng, Jen-Hsien; Chou, Chang-Hung

2013-01-01

Rhododendron formosanum is distributed widely in the central mountains in Taiwan and the major allelopathic compound in the leaves has been identified as (-)-catechin, which is also a major allelochemical of an invasive spotted knapweed in North America. Soil microorganisms play key roles in ecosystems and influence various important processes, including allelopathy. However, no microorganism has been identified as an allelochemical mediator. This study focused on the role of microorganisms in the allelopathic effects of R. formosanum. The microorganism population in the rhizosphere of R. formosanum was investigated and genetic analysis revealed that the predominant genera of microorganisms in the rhizosphere of R. formosanum were Pseudomonas, Herbaspirillum, and Burkholderia. The dominant genera Pseudomonas utilized (-)-catechin as the carbon source and catalyzed the conversion of (-)-catechin into protocatechuic acid in vitro. The concentrations of allelochemicals in the soil were quantified by liquid chromatography-electrospray ionization/tandem mass spectrometry. The concentration of (-)-catechin in the soil increased significantly during the extreme rainfall in the summer season and suppressed total bacterial populations. Protocatechuic acid accumulation was observed while total bacterial populations increased abundantly in both laboratory and field studies. Allelopathic interactions were tested by evaluating the effects of different allelochemicals on the seed germination, radicle growth, and photosynthesis system II of lettuce. Protocatechuic acid exhibited higher phytotoxicity than (-)-catechin did and the effect of (-)-catechin on the inhibition of seed germination was enhanced by combining it with protocatechuic acid at a low concentration. This study revealed the significance of the allelopathic interactions between R. formosanum and microorganisms in the rhizosphere. These findings demonstrate that knowledge regarding the precise biotransformation

The impact of microbial biotransformation of catechin in enhancing the allelopathic effects of Rhododendron formosanum.

Directory of Open Access Journals (Sweden)

Chao-Min Wang

Full Text Available Rhododendron formosanum is distributed widely in the central mountains in Taiwan and the major allelopathic compound in the leaves has been identified as (--catechin, which is also a major allelochemical of an invasive spotted knapweed in North America. Soil microorganisms play key roles in ecosystems and influence various important processes, including allelopathy. However, no microorganism has been identified as an allelochemical mediator. This study focused on the role of microorganisms in the allelopathic effects of R. formosanum. The microorganism population in the rhizosphere of R. formosanum was investigated and genetic analysis revealed that the predominant genera of microorganisms in the rhizosphere of R. formosanum were Pseudomonas, Herbaspirillum, and Burkholderia. The dominant genera Pseudomonas utilized (--catechin as the carbon source and catalyzed the conversion of (--catechin into protocatechuic acid in vitro. The concentrations of allelochemicals in the soil were quantified by liquid chromatography-electrospray ionization/tandem mass spectrometry. The concentration of (--catechin in the soil increased significantly during the extreme rainfall in the summer season and suppressed total bacterial populations. Protocatechuic acid accumulation was observed while total bacterial populations increased abundantly in both laboratory and field studies. Allelopathic interactions were tested by evaluating the effects of different allelochemicals on the seed germination, radicle growth, and photosynthesis system II of lettuce. Protocatechuic acid exhibited higher phytotoxicity than (--catechin did and the effect of (--catechin on the inhibition of seed germination was enhanced by combining it with protocatechuic acid at a low concentration. This study revealed the significance of the allelopathic interactions between R. formosanum and microorganisms in the rhizosphere. These findings demonstrate that knowledge regarding the precise

Activation of р-450-depended monooxygenases changing immunotoxicity of phosphoroorganic compounds due to their metabolism character

Directory of Open Access Journals (Sweden)

P.F. Zabrodsky

2010-03-01

Full Text Available It was established that the application of the monooxygenase system inductors (MSI of phenobarbital and benzonal up to acute poisoning of animals by trichlorfom in a dose of 1,0 LD50, metabolized in the organism till production of compounds with higher toxicity caused its immunotoxic properties increase. The experiment was carried out on outbred white rats. the acute dimethyldichlorvinylphosphate (1,0 LD50 poisoning, biotransformation of which proceeded with formation of less-toxic and non-toxic compounds after MSI introduction, caused its decrease of suppression influence on immunity system indices

Lignin peroxidase mediated biotransformations useful in the biocatalytic production of vanillin

NARCIS (Netherlands)

Have, ten R.

2000-01-01

This research concentrates on lignin peroxidase (LiP) mediated biotrans-formations that are useful in producing vanillin.

In order to obtain this extracellular enzyme, the white-rot fungus Bjerkandera sp. strain BOS55 was cultivated on nitrogen rich

Tissue-specific bioconcentration and biotransformation of cypermethrin and chlorpyrifos in a native fish (Jenynsia multidentata) exposed to these insecticides singly and in mixtures.

Science.gov (United States)

Bonansea, Rocío Inés; Marino, Damián J G; Bertrand, Lidwina; Wunderlin, Daniel A; Amé, María Valeria

2017-07-01

The aim of the present study was to evaluate the accumulation of cypermethrin and chlorpyrifos when the fish Jenynsia multidentata was exposed to these pesticides singly and in technical and commercial mixtures. Adult female fish were exposed over 96 h to 0.04 μg/L of cypermethrin; 0.4 μg/L of chlorpyrifos; 0.04 μg/L of cypermethrin + 0.4 μg/L of chlorpyrifos in a technical mixture; and 0.04 μg/L of cypermethrin + 0.4 μg/L of chlorpyrifos in a mixture of commercial products. Fish exposed to cypermethrin accumulated this compound only in muscle, probably because of the low biotransformation capacity of this organ and the induction of cytochrome P4501A1 (CYP1A1) expression in the liver. The accumulation of chlorpyrifos occurred in fish exposed to the insecticide (intestine > liver > gills) even when these fish had higher gluthatione-S-transferase (GST) activity in gills and P-glycoprotein (P-gp) expression in the liver, compared with the control. Fish exposed to the technical mixture showed cypermethrin accumulation (liver > intestine > gills) with higher levels than those measured in fish after only cypermethrin exposure. Higher expression levels of CYP1A1 in the liver were also observed compared with the Control. Fish exposed to the commercial mixture accumulated both insecticides (cypermethrin: intestine > gills and chlorpyrifos: liver > intestine > gills > muscle). In the organs where accumulation occurred, biotransformation enzymes were inhibited. Consequently, the commercial formulation exposure provoked the highest accumulation of cypermethrin and chlorpyrifos in J. multidentata, possibly associated with the biotransformation system inhibition. Environ Toxicol Chem 2017;36:1764-1774. © 2016 SETAC. © 2016 SETAC.

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro.

Science.gov (United States)

Rankin, Gary O; Tyree, Connor; Pope, Deborah; Tate, Jordan; Racine, Christopher; Anestis, Dianne K; Brown, Kathleen C; Dial, Mason; Valentovic, Monica A

2017-05-31

This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15-120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.

A fungal metallo-beta-lactamase necessary for biotransformation of maize phytoprotectant compounds

Science.gov (United States)

Xenobiotic compounds such as phytochemicals, microbial metabolites, and agrochemicals can impact the diversity and frequency of fungal species occurring in agricultural environments. Resistance to xenobiotics may allow plant pathogenic fungi to dominate the overall fungal community, with potential ...

Biotransformation and recovery of the isoflavones genistein and daidzein from industrial antibiotic fermentations

Science.gov (United States)

Weber, J. Mark; Reeves, Andrew R.; Seshadri, Ramya; Cernota, William H.; Gonzalez, Melissa C.; Gray, Danielle L.; Wesley, Roy K.

2013-01-01

The objective of this study was to follow the metabolic fate of isoflavone glucosides from the soybean meal in a model industrial fermentation to determine if commercially useful isoflavones could be harvested as coproducts from the spent broth at the end of the fermentation. The isoflavone aglycones, genistein and daidzein, together make up 0.1 - 0.2% of the soybean meal by weight but serve no known function in the manufacturing process. After feeding genistein to washed cells of the erythromycin-producing organism, Saccharopolyspora erythraea, the first biotransformation product (Gbp1) was determined by x-ray crystallography to be genistein-7-O-α-rhamnoside (rhamnosylgenistein). Subsequent feeding of rhamnosylgenistein to growing cells of S. erythraea led to the production of a second biotransformation product, Gbp2. Chromatographic evidence suggested that Gbp2 accumulated in the spent broth of the erythromycin fermentation. When the spent broth was hydrolyzed with acid or industrial enzyme preparations the isoflavone biotransformation products were returned back to their parental forms, genistein and daidzein, which were then recovered as coproducts. Desirable features of this method are that it does not require modification of the erythromycin manufacturing process or genetic engineering of the producing organism to be put into practice. A preliminary investigation of five additional antibiotic fermentations of industrial importance were also found to have isoflavone coproduct potential. PMID:23604533

Biotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd)

International Nuclear Information System (INIS)

Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.; Tveit, Ann; Dekant, Wolfgang

2013-01-01

trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is negative in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected for 48 h after the end of the exposure. Study specimens were analyzed for metabolites using 19 F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t 1/2 1/2 < 6 h). ► Glutathione adduct as predominant in vitro metabolite in all tested species. ► Toxic metabolites could not be detected in any great extent

Optimization of Malaxation Process using Major Aroma Compounds in Virgin Olive Oil

OpenAIRE

Cevik,Serife; Ozkan,Gulcan; Kıralan,Mustafa

2016-01-01

ABSTRACT Optimization of major aroma compounds in olive oils produced from fruits at three maturity stages wasstudied. A central composite design was used for the optimization of malaxation conditions of temperature and times, each at five levels with 13 runs including five central points. The responses of interest were trans-2-hexenal and hexanal, which were investigated and their contents were optimized. A full quadratic second order regression model including the linear, quadratic, and two...

Biotransformation of d-Limonene to (+) trans-Carveol by Toluene-Grown Rhodococcus opacus PWD4 Cells

Science.gov (United States)

Duetz, Wouter A.; Fjällman, Ann H. M.; Ren, Shuyu; Jourdat, Catherine; Witholt, Bernard

2001-01-01

The toluene-degrading strain Rhodococcus opacus PWD4 was found to hydroxylate d-limonene exclusively in the 6-position, yielding enantiomerically pure (+) trans-carveol and traces of (+) carvone. This biotransformation was studied using cells cultivated in chemostat culture with toluene as a carbon and energy source. The maximal specific activity of (+) trans-carveol formation was 14.7 U (g of cells [dry weight])−1, and the final yield was 94 to 97%. Toluene was found to be a strong competitive inhibitor of the d-limonene conversion. Glucose-grown cells did not form any trans-carveol from d-limonene. These results suggest that one of the enzymes involved in toluene degradation is responsible for this allylic monohydroxylation. Another toluene degrader (Rhodococcus globerulus PWD8) had a lower specific activity but was found to oxidize most of the formed trans-carveol to (+) carvone, allowing for the biocatalytic production of this flavor compound. PMID:11375201

Optimization of biotransformation from phytosterol to androstenedione by a mutant Mycobacterium neoaurum ZJUVN-08*

Science.gov (United States)

Zhang, Xiao-yan; Peng, Yong; Su, Zhong-rui; Chen, Qi-he; Ruan, Hui; He, Guo-qing

2013-01-01

Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-β-cyclodextrin (HP-β-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-β-CD to PS 1.92:1, 8.98 g/L PS, and at 120 h of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process. PMID:23365012

Optimization of biotransformation from phytosterol to androstenedione by a mutant Mycobacterium neoaurum ZJUVN-08.

Science.gov (United States)

Zhang, Xiao-yan; Peng, Yong; Su, Zhong-rui; Chen, Qi-he; Ruan, Hui; He, Guo-qing

2013-02-01

Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-β-cyclodextrin (HP-β-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-β-CD to PS 1.92:1, 8.98 g/L PS, and at 120 h of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process.

Biotransformation effect of Bombyx Mori L. may play an important role in treating diabetic nephropathy.

Science.gov (United States)

Zhang, Lei; Zhang, La; Li, Yin; Guo, Xin-Feng; Liu, Xu-Sheng

2016-11-01

Compared with herbal drugs, medicine processed from animals (animal medicine) was thought to have more bioactive substances and higher activities. Biotransformation effect often plays an important role in their effect. However, researches about effect of animal medicine on diabetic nephropathy and applying animal medicine as natural bio-transformer were seldom reported. The purpose of this paper was to reveal the use of Bombyx Mori L. on diabetic nephropathy from ancient to modern times. The classical literature indicated that Saosi Decoction (), which contains Bombyx Mori L. or silkworm cocoon, was applied to treat disorders congruent with modern disease diabetic nephropathy from the Ming to Qing Dynasty in ancient China. Modern studies showed that Bombyx Mori L. contains four main active constituents. Among these, 1-deoxynojirimycin (1-DNJ) and quercetin showed promising potential to be new agents in diabetic nephropathy treatment. The concentrations of 1-DNJ and the activities of quercetin in Bombyx Mori L. are higher than in mulberry leaves, because of the biotransformation in the Bombyx Mori L. body. However, these specifific components need further human and mechanistic studies to determine their therapeutic potential for this challenging condition.

Biotransformation and nephrotoxicity of ochratoxin B in rats

International Nuclear Information System (INIS)

Mally, Angela; Keim-Heusler, Heike; Amberg, Alexander; Kurz, Michael; Zepnik, Herbert; Mantle, Peter; Voelkel, Wolfgang; Hard, Gordon C.; Dekant, Wolfgang

2005-01-01

Ochratoxin B (OTB), a secondary metabolite of Aspergillus ochraceus, is the nonchlorinated analogue of the mycotoxin ochratoxin A (OTA), which is one of the most potent renal carcinogens in rodents. Despite the closely related structure, OTB is considered to be of much lower toxicity. OTA is poorly metabolized and slowly eliminated, and this may play an important role in OTA toxicity, carcinogenicity, and organ specificity. Since little is known regarding biotransformation and renal toxicity of OTB, the aim of this study was to investigate biotransformation of OTB in rats and to characterize the nephrotoxicity and cytotoxicity of OTB. Male F344 rats were administered either a single dose of OTB (10 mg/kg bw) or repeated doses (2 mg/kg bw, 5 days/week for 2 weeks) and euthanized 72 h after the last dosing. In proximal tubule cells of animals treated with a single high dose of OTB, a slight increase in mitotic figures was observed, but no treatment-related changes were evident in clinical chemistry, in renal function, and histopathology after repeated administration. Excretion of OTB and metabolites in urine and feces was analyzed using both HPLC with fluorescence detection and LC-MS/MS. Ochratoxin beta, which results from cleavage of the peptide bond, was the major metabolite excreted in urine in addition to small amounts of 4-hydroxy-OTB. In total, 19% of the administered dose was recovered as OTB and ochratoxin beta in urine and feces within 72 h after a single dose. In contrast to OTA, no tissue-specific retention of OTB was evident after single and repeated administration. In LLC-PK1 cells, a renal cell culture system that retains much of the specific features of the proximal tubule, only minor differences in the extent of cytotoxicity of OTA and OTB were observed. At low concentrations (< 25 μM), treatment with OTA was slightly more toxic, whereas reduction in cell viability was similar at concentrations up to 100 μM. In summary, these data suggest that OTA

Engineering Issue Paper: Biotransformation Pathways of Dimethylarsinic (Cacodylic) Acid in the Environment

Science.gov (United States)

This EIP summarizes the state of the science regarding the biotransformation of DMA(V) and was developed from peer-reviewed literature, scientific documents, EPA reports, internet sources, input from experts in the field, and other pertinent sources. This EIP includes a review o...

BIOACCUMULATION AND BIOTRANSFORMATION OF CHIRAL TRIAZOLE FUNGICIDES IN RAINBOW TROUT (ONCORHYNCHUS MYKISS)

Science.gov (United States)

There are very little data on the bioaccumulation and biotransformation of current-use pesticides (CUPs) despite the fact that such data are critical in assessing their fate and potential toxic effects in aquatic organisms. To help address this issue, juvenile rainbow trout (Onco...

Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration

International Nuclear Information System (INIS)

Voelkel, Wolfgang; Colnot, Thomas; Schauer, Ute M.D.; Broschard, Thomas H.; Dekant, Wolfgang

2006-01-01

3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In this study, the toxicokinetics and biotransformation of 4-MBC were characterized in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn oil. Metabolites formed were characterized and the kinetics of elimination for 4-MBC and its metabolites from blood and with urine were determined. Metabolites of 4-MBC were characterized by 1 H NMR and LC-MS/MS as 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. After oral administration of 4-MBC, only very low concentrations of 4-MBC were present in blood and the peak concentrations of 3-(4-carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC; blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection. Blood concentration of 4-MBC and 3-(4-carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then decreased with half-lives of approximately 15 h. No major differences in peak blood levels between male and female rats were seen. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. However, urinary excretion of 4-MBC-metabolites represents only a minor pathway of elimination for 4-MBC, since most of the applied dose was recovered in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor

Biotransformation of (S)-cis-verbenol with Nocardia corallina B-276

Energy Technology Data Exchange (ETDEWEB)

Manjarrez, Norberto; Perez, Herminia I.; Solis, Aida; Luna, Hector; Lievano, Ricardo; Ramirez, Mario [Universidad Autonoma Metropolitana, Mexico, D.F. (Mexico). Unidad Xochimilco. Dept. de Sistemas Biologicos]. E-mail: maan@correo.xoc.uam.mx

2007-07-01

The biotransformation of (S)-cis-verbenol with Nocardia corallina was investigated using two methods: Suspension of cells in a phosphate buffer (pH 7) with various substrate:cells ratios; and bioreactor of 3-L with cells in the culture media. Both gave (1S)-(-)-verbenone with excellent yields ranging from >99 to 98%, at scale of 0.7 and 7 mmol respectively. (author)

Biotransformation of (S)-cis-verbenol with Nocardia corallina B-276

International Nuclear Information System (INIS)

Manjarrez, Norberto; Perez, Herminia I.; Solis, Aida; Luna, Hector; Lievano, Ricardo; Ramirez, Mario

2007-01-01

The biotransformation of (S)-cis-verbenol with Nocardia corallina was investigated using two methods: Suspension of cells in a phosphate buffer (pH 7) with various substrate:cells ratios; and bioreactor of 3-L with cells in the culture media. Both gave (1S)-(-)-verbenone with excellent yields ranging from >99 to 98%, at scale of 0.7 and 7 mmol respectively. (author)

Enantioselective analysis of propranolol and 4-hydroxypropranolol by CE with application to biotransformation studies employing endophytic fungi.

Science.gov (United States)

Borges, Keyller Bastos; Pupo, Mônica Tallarico; Bonato, Pierina Sueli

2009-11-01

A CE method is described for the enantioselective analysis of propranolol (Prop) and 4-hydroxypropranolol (4-OH-Prop) in liquid Czapek medium with application in the study of the enantioselective biotransformation of Prop by endophytic fungi. The electrophoretic conditions previously optimized were as follows: an uncoated fused-silica capillary, 4% w/v carboxymethyl-beta-CD in 25 mmol/L triethylamine/phosphoric acid (H(3)PO(4)) buffer at pH 9 as running electrolyte and 17 kV of voltage. UV detection was carried out at 208 nm. Liquid-liquid extraction using diethyl ether: ethyl acetate (1:1 v/v) as extractor solvent was employed for sample preparation. The calibration curves were linear over the concentration range of 0.25-10.0 microg/mL for each 4-OH-Prop enantiomer and 0.10-10.0 microg/mL for each Prop enantiomer (r>or=0.995). Within-day and between-day relative standard deviations and relative errors for precision and accuracy were lower than 15% for all the enantiomers. Finally, the validated method was used to evaluate Prop biotransformation in its mammalian metabolite 4-OH-Prop by some selected endophytic fungi. The screening of five strains of endophytic fungi was performed and all of them could biotransform Prop to some extent. Specifically, Glomerella cingulata (VA1) biotransformed 47.8% of (-)-(S)-Prop to (-)-(S)-4-OH-Prop with no formation of (+)-(R)-4-OH-Prop in 72 h of incubation.

Salinivibrio costicola GL6, a Novel Isolated Strain for Biotransformation of Caffeine to Theobromine Under Hypersaline Conditions.

Science.gov (United States)

Ashengroph, Morahem

2017-01-01

The present study has been conducted towards isolation of moderately halophilic bacteria capable of transforming caffeine into theobromine. A total of 45 caffeine-degrading moderate halophiles were enriched from hypersaline lakes and examined for the biotransformation of caffeine to theobromine by thin-layer chromatography (TLC) and high-performance liquid chromatography analyses. Strain GL6, giving the highest yield of theobromine, was isolated from the Hoz Soltan Lake, 20 % w/v salinity, central Iran, and identified as Salinivibrio costicola based on morphological and biochemical features as well as its 16S rRNA gene sequence analysis (GeneBank Accession No. KT378066) and DNA-DNA relatedness. The biotransformation of caffeine with strain GL6 leads to the formation of two metabolites, identified as theobromine and paraxanthine, but the yield of paraxanthine was much lower. Further study on the production of theobromine from caffeine under resting cell experiment was carried out subsequently. The optimal yield of theobromine (56 %) was obtained after a 32-h incubation using 5 mM of caffeine and 15 g l -1 (wet weight) of biomass in 0.1 M saline phosphate buffer (pH 7.0 and 10 % w/v NaCl) under agitation 180 rpm at 30 °C. The biotransformed theobromine was purified by preparative TLC and subjected to FTIR and mass spectroscopy for chemical identification. This is the first evidence for biotransformation of caffeine into theobromine by strains of the genus Salinivibrio.

Influence of temperature on nucleus degradation of 4-androstene-3, 17-dione in phytosterol biotransformation by Mycobacterium sp.

Science.gov (United States)

Xu, X W; Gao, X Q; Feng, J X; Wang, X D; Wei, D Z

2015-07-01

One of the steroid intermediates, 4-androstene-3, 17-dione (AD), in the biotransformation of phytosterols is valuable for the production of steroid medicaments. However, its degradation during the conversion process is one of the main obstacles to obtain high yields. In this study, the effect of temperature on nucleus degradation during microbial biotransformation of phytosterol was investigated. The results indicated that microbial degradation of phytosterol followed the AD-ADD-'9-OH-ADD' pathway, and that two important reactions involved in nucleus degradation, conversions of AD to ADD and ADD to 9-OH-ADD, were inhibited at 37°C. With a change in the culture temperature from 30 to 37°C, nucleus degradation was reduced from 39·9% to 17·6%, due to inhibition of the putative KstD and Ksh. These results suggested a simple way to decrease the nucleus degradation in phytosterol biotransformation and a new perspective on the possibilities of modifying the metabolism of strains used in industrial applications. Nucleus degradation of products is one of the main problems encountered during phytosterol biotransformation. To solve this problem, the effect of temperature on nucleus degradation was investigated in the industrial production of steroid intermediates. The results are also helpful to the genetic modification of sterol-producing strains. © 2015 The Society for Applied Microbiology.

Biotransformation of tetrachloroethylene to trichloroethylene, dichloroethylene, vinyl chloride, and carbon dioxide under methanogenic conditions

International Nuclear Information System (INIS)

Vogel, T.M.; McCarty, P.L.

1985-01-01

Tetrachloroethylene (PCE) and trichloroethylene (TCE), common industrial solvents, are among the most frequent contaminants found in groundwater supplies. Due to the potential toxicity and carcinogenicity of chlorinated ethylenes, knowledge about their transformation potential is important in evaluating their environmental fate. The results of this study confirm that PCE can be transformed by reductive dehalogenation to TCE, dichloroethylene, and vinyl chloride (VC) under anaerobic conditions. In addition, [ 14 C]PCE was at least partially mineralized to CO 2 . Mineralization of 24% of the PCE occurred in a continuous-flow fixed-film methanogenic column with a liquid detention time of 4 days. TCE was the major intermediate formed, but traces of dichloroethylene isomers and VC were also found. In other column studies under a different set of methanogenic conditions, nearly quantitative conversion of PCE to VC was found. These studies clearly demonstrate that TCE and VC are major intermediates in PCE biotransformation under anaerobic conditions and suggest that the potential exists for the complete mineralization of PCE to CO 2 in soil and aquifer systems and in biological treatment processes

Microbial Detoxification of Deoxynivalenol (DON), Assessed via a Lemna minor L. Bioassay, through Biotransformation to 3-epi-DON and 3-epi-DOM-1.

Science.gov (United States)

Vanhoutte, Ilse; De Mets, Laura; De Boevre, Marthe; Uka, Valdet; Di Mavungu, José Diana; De Saeger, Sarah; De Gelder, Leen; Audenaert, Kris

2017-02-13

Mycotoxins are toxic metabolites produced by fungi. To mitigate mycotoxins in food or feed, biotransformation is an emerging technology in which microorganisms degrade toxins into non-toxic metabolites. To monitor deoxynivalenol (DON) biotransformation, analytical tools such as ELISA and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) are typically used. However, these techniques do not give a decisive answer about the remaining toxicity of possible biotransformation products. Hence, a bioassay using Lemna minor L. was developed. A dose-response analysis revealed significant inhibition in the growth of L. minor exposed to DON concentrations of 0.25 mg/L and higher. Concentrations above 1 mg/L were lethal for the plant. This bioassay is far more sensitive than previously described systems. The bioassay was implemented to screen microbial enrichment cultures, originating from rumen fluid, soil, digestate and activated sludge, on their biotransformation and detoxification capability of DON. The enrichment cultures originating from soil and activated sludge were capable of detoxifying and degrading 5 and 50 mg/L DON. In addition, the metabolites 3-epi-DON and the epimer of de-epoxy-DON (3-epi-DOM-1) were found as biotransformation products of both consortia. Our work provides a new valuable tool to screen microbial cultures for their detoxification capacity.

Microbial Detoxification of Deoxynivalenol (DON, Assessed via a Lemna minor L. Bioassay, through Biotransformation to 3-epi-DON and 3-epi-DOM-1

Directory of Open Access Journals (Sweden)

Ilse Vanhoutte

2017-02-01

Full Text Available Mycotoxins are toxic metabolites produced by fungi. To mitigate mycotoxins in food or feed, biotransformation is an emerging technology in which microorganisms degrade toxins into non-toxic metabolites. To monitor deoxynivalenol (DON biotransformation, analytical tools such as ELISA and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS are typically used. However, these techniques do not give a decisive answer about the remaining toxicity of possible biotransformation products. Hence, a bioassay using Lemna minor L. was developed. A dose–response analysis revealed significant inhibition in the growth of L. minor exposed to DON concentrations of 0.25 mg/L and higher. Concentrations above 1 mg/L were lethal for the plant. This bioassay is far more sensitive than previously described systems. The bioassay was implemented to screen microbial enrichment cultures, originating from rumen fluid, soil, digestate and activated sludge, on their biotransformation and detoxification capability of DON. The enrichment cultures originating from soil and activated sludge were capable of detoxifying and degrading 5 and 50 mg/L DON. In addition, the metabolites 3-epi-DON and the epimer of de-epoxy-DON (3-epi-DOM-1 were found as biotransformation products of both consortia. Our work provides a new valuable tool to screen microbial cultures for their detoxification capacity.

Obtaining Low Rank Coal Biotransforming Bacteria from Microhabitats Enriched with Carbonaceous Residues

International Nuclear Information System (INIS)

Valero Valero, Nelson; Rodriguez Salazar, Luz Nidia; Mancilla Gomez, Sandra; Contreras Bayona, Leydis

2012-01-01

Bacteria capable of low rank coal (LRC) biotransform were isolated from environmental samples altered with coal in the mine The Cerrejon. A protocol was designed to select strains more capable of LRC biotransform, the protocol includes isolation in a selective medium with LRC powder, qualitative and quantitative tests for LRC solubilization in solid and liquid culture medium. Of 75 bacterial strains isolated, 32 showed growth in minimal salts agar with 5 % carbon. The strains that produce higher values of humic substances (HS) have a mechanism of solubilization associated with pH changes in the culture medium, probably related to the production of extracellular alkaline substances by bacteria. The largest number of strains and bacteria with more solubilizing activity on LRC were isolated from sludge with high content of carbon residue and rhizosphere of Typha domingensis and Cenchrus ciliaris grown on sediments mixed with carbon particles, this result suggests that obtaining and solubilization capacity of LRC by bacteria may be related to the microhabitat where the populations originated.

Modulation of porcine biotransformation enzymes by anthelmintic therapy with fenbendazole and flubendazole.

Science.gov (United States)

Savlík, M; Fimanová, K; Szotáková, B; Lamka, J; Skálová, L

2006-06-01

Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.

ANAEROBIC DDT BIOTRANSFORMATION: ENHANCEMENT BY APPLICATION OF SURFACTANTS AND LOW OXIDATION REDUCTION POTENTIAL

Science.gov (United States)

Enhancement of anaerobic DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) biotransformation by mixed cultures was studied with application of surfactants and oxidation reduction potential reducing agents. Without amendments, DDT transformation resulted mainly in the pr...

EFFECTS OF ANESTHESIA (MS222) ON LIVER BIOTRANSFORMATION IN RAINBOW TROUT (ONCORHYNCHUS MYKISS)

Science.gov (United States)

Tricaine methanesulfonate (3-aminobenzoic acid ethyl ester methanesulfonate; MS222) is a widely used fish anaesthetic. While there have been several studies addressing the impact of its use on subsequently measured biotransformation rates, the measured influence on normal functio...

Biotransformation of an africanane sesquiterpene by the fungus Mucor plumbeus.

Science.gov (United States)

Fraga, Braulio M; Díaz, Carmen E; Amador, Leonardo J; Reina, Matías; López-Rodriguez, Matías; González-Coloma, Azucena

2017-03-01

Biotransformation of 8β-hydroxy-african-4(5)-en-3-one angelate by the fungus Mucor plumbeus afforded as main products 6α,8β-dihydroxy-african-4(5)-en-3-one 8β-angelate and 1α,8β-dihydroxy-african-4(5)-en-3-one 8β-angelate, which had been obtained, together with the substrate, from transformed root cultures of Bethencourtia hermosae. This fact shows that the enzyme system involved in these hydroxylations in both organisms, the fungus and the plant, acts with the same regio- and stereospecificity. In addition another twelve derivatives were isolated in the incubation of the substrate, which were identified as the (2'R,3'R)- and (2'S,3'S)-epoxy derivatives of the substrate and of the 6α- and 1α-hydroxy alcohols, the 8β-(2'R,3'R)- and 8β-(2'S,3'S)-epoxyangelate of 8β,15-dihydroxy-african-4(5)-en-3-one, the hydrolysis product of the substrate, and three isomers of 8β-hydroxy-african-4(5)-en-3-one 2ξ,3ξ-dihydroxy-2-methylbutanoate. The insect antifeedant effects of the pure compounds were tested against chewing and sucking insect species along with their selective cytotoxicity against insect (Sf9) and mammalian (CHO) cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of biotransformation, sorption and mineralization of "1"4C-labelled sulfamethoxazole under different redox conditions

International Nuclear Information System (INIS)

Alvarino, T.; Nastold, P.; Suarez, S.; Omil, F.; Corvini, P.F.X.; Bouju, H.

2016-01-01

"1"4C-sulfamethoxazole biotransformation, sorption and mineralization was studied with heterotrophic and autotrophic biomass under aerobic and anoxic conditions, as well as with anaerobic biomass. The "1"4C-radiolabelled residues distribution in the solid, liquid and gas phases was closely monitored along a total incubation time of 190 h. Biotransformation was the main removal mechanism, mineralization and sorption remaining below 5% in all the cases, although the presence of a carbon source exerted a positive effect on the mineralization rate by the aerobic heterotrophic bacteria. In fact, an influence of the type of primary substrate and the redox potential was observed in all cases on the biotransformation and mineralization rates, since an enhancement of the removal rate was observed when an external carbon source was used as a primary substrate under aerobic conditions, while a negligible effect was observed under nitrifying conditions. In the liquid phases collected from all assays, up to three additional peaks corresponding to "1"4C-radiolabelled residues were detected. The highest concentration was observed under anaerobic conditions, where two radioactive metabolites were detected representing each around 15% of the total applied radioactivity after 180 h incubation. One of the metabolites detected under anoxic and anaerobic conditions, is probably resulting from ring cleavage of the isoxazole ring. - Highlights: • New procedure based on "1"4C to determine sulfamethoxazole (SMX) removal • Complete SMX mass balances in solid, liquid and gas phases • Quantification of SMX biotransformation, mineralization and sorption • Influence of the primary metabolism and redox potential on SMX removal • SMX metabolites have been detected and a possible chemical structure was proposed.

Role of biotransformation, sorption and mineralization of {sup 14}C-labelled sulfamethoxazole under different redox conditions

Energy Technology Data Exchange (ETDEWEB)

Alvarino, T., E-mail: teresa.alvarino@usc.es [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Nastold, P. [Institute for Ecopreneurship, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, 40 Grundenstrasse, CH 4132 Muttenz (Switzerland); Suarez, S.; Omil, F. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Corvini, P.F.X. [Institute for Ecopreneurship, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, 40 Grundenstrasse, CH 4132 Muttenz (Switzerland); State Key Laboratory for Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Bouju, H. [Institute for Ecopreneurship, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, 40 Grundenstrasse, CH 4132 Muttenz (Switzerland)

2016-01-15

{sup 14}C-sulfamethoxazole biotransformation, sorption and mineralization was studied with heterotrophic and autotrophic biomass under aerobic and anoxic conditions, as well as with anaerobic biomass. The {sup 14}C-radiolabelled residues distribution in the solid, liquid and gas phases was closely monitored along a total incubation time of 190 h. Biotransformation was the main removal mechanism, mineralization and sorption remaining below 5% in all the cases, although the presence of a carbon source exerted a positive effect on the mineralization rate by the aerobic heterotrophic bacteria. In fact, an influence of the type of primary substrate and the redox potential was observed in all cases on the biotransformation and mineralization rates, since an enhancement of the removal rate was observed when an external carbon source was used as a primary substrate under aerobic conditions, while a negligible effect was observed under nitrifying conditions. In the liquid phases collected from all assays, up to three additional peaks corresponding to {sup 14}C-radiolabelled residues were detected. The highest concentration was observed under anaerobic conditions, where two radioactive metabolites were detected representing each around 15% of the total applied radioactivity after 180 h incubation. One of the metabolites detected under anoxic and anaerobic conditions, is probably resulting from ring cleavage of the isoxazole ring. - Highlights: • New procedure based on {sup 14}C to determine sulfamethoxazole (SMX) removal • Complete SMX mass balances in solid, liquid and gas phases • Quantification of SMX biotransformation, mineralization and sorption • Influence of the primary metabolism and redox potential on SMX removal • SMX metabolites have been detected and a possible chemical structure was proposed.

Attenuation of trace organic compounds (TOrCs) inbioelectrochemical systems

KAUST Repository

Werner, Craig M.

2015-04-01

Microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) are two types of microbial bioelectrochemical systems (BESs) that use microorganisms to convert chemical energy in wastewaters into useful energy products such as (bio)electricity (MFC) or hydrogen gas (MEC). These two systems were evaluated for their capacity to attenuate trace organic compounds (TOrCs), commonly found in municipal wastewater, under closed circuit (current generation) and open circuit (no current generation) conditions, using acetate as the carbon source. A biocide was used to evaluate attenuation in terms of biotransformation versus sorption. The difference in attenuation observed before and after addition of the biocide represented biotransformation, while attenuation after addition of a biocide primarily indicated sorption. Attenuation of TOrCs was similar in MFCs and MECs for eight different TOrCs, except for caffeine and trimethoprim where slightly higher attenuation was observed in MECs. Electric current generation did not enhance attenuation of the TOrCs except for caffeine, which showed slightly higher attenuation under closed circuit conditions in both MFCs and MECs. Substantial sorption of the TOrCs occurred to the biofilm-covered electrodes, but no consistent trend could be identified regarding the physico-chemical properties of the TOrCs tested and the extent of sorption. The octanol-water distribution coefficient at pH 7.4 (log DpH 7.4) appeared to be a reasonable predictor for sorption of some of the compounds (carbamazepine, atrazine, tris(2-chloroethyl) phosphate and diphenhydramine) but not for others (N,N-Diethyl-meta-toluamide). Atenolol also showed high levels of sorption despite being the most hydrophilic in the suite of compounds studied (log DpH 7.4=-1.99). Though BESs do not show any inherent advantages over conventional wastewater treatment, with respect to TOrC removal, overall removals in BESs are similar to that reported for conventional wastewater

Skin: Major target organ of allergic reactions to small molecular weight compounds

International Nuclear Information System (INIS)

Merk, Hans F.; Baron, Jens M.; Neis, Mark M.; Obrigkeit, Daniela Hoeller; Karlberg, Ann-Therese

2007-01-01

Skin is a major target organ for allergic reactions to small molecular weight compounds. Drug allergic reactions may be life-threatening such as in the case of anaphylactic reactions or bullous drug reactions and occur in about 5% of all hospitalized patients. Allergic contact dermatitis has an enormous influence on the social life of the patient because it is the most frequent reason for occupational skin diseases and the treatment and prevention of this disease cost approximately Euro 3 billion per year in Germany. The different proposed pathophysiological pathways leading to a drug eruption are discussed in this paper. All major enzymes which are involved in the metabolism of xenobiotica were shown to be present in skin. Evidence supporting the role of metabolism in the development of drug allergy and allergic contact dermatitis is demonstrated in the example of sulphonamides and fragrances

Bioaccumulation Behavior of Pharmaceuticals and Personal Care Products in Adult Zebrafish (Danio rerio): Influence of Physical-Chemical Properties and Biotransformation.

Science.gov (United States)

Chen, Fangfang; Gong, Zhiyuan; Kelly, Barry C

2017-10-03

The factors influencing bioaccumulation of pharmaceuticals and personal care products (PPCPs) in aquatic organisms are not well understood. The present study involved a comprehensive laboratory investigation to assess the bioaccumulation behavior of several PPCPs in adult zebrafish (Danio rerio). The studied PPCPs included several ionogenic organic compounds (IOCs) such as weak acids and weak bases. Experiments involved two exposure groups (high and low) and a control group, with a 6 day aqueous exposure, followed by a 7 day depuration phase under flow-through conditions. Uptake rate constants (k u ) ranged between 0.19 and 8610 L·kg -1 ·d -1 , while depuration rate constants (k d ) ranged between 0.14 and 5.14 d -1 in different fish tissues. Steady-state bioconcentration factor (BCF ss ) values varied widely among the studied PPCPs, ranging from 0.09 to 6,460. In many cases, BCF ss values of individual PPCPs differed substantially among different fish tissues. Positive linear relationships were observed between log BCF ss values and physical-chemical properties such as octanol-water distribution coefficients (log D ow ), membrane-water distribution coefficients (log D mw ), albumin-water distribution coefficients (log D BSAw ), and muscle protein-water distribution coefficients (log D mpw ), indicating the importance of lipid-, phospholipid-, and protein-water partitioning. The results also showed that for many PPCPs, the estimated whole-body metabolism rate constant (k m ) values were comparable to the observed depuration rate (k d ), indicating that metabolism plays a major role in the overall elimination of these compounds in zebrafish. An exception was sertraline, which exhibited a k d value (0.4-0.5 d -1 ) that was much higher than the estimated whole-body k m (0.03 d -1 ). Overall, the results help to better understand the influence of physical-chemical properties and biotransformation on bioaccumulation behavior of these contaminants of concern in aquatic

Morphine dependence is attenuated by red ginseng extract and ginsenosides Rh2, Rg3, and compound K

OpenAIRE

Yayeh, Taddesse; Yun, Kyunghwa; Jang, Soyong; Oh, Seikwan

2016-01-01

Background: Red ginseng and ginsenosides have shown plethoric effects against various ailments. However, little is known regarding the effect of red ginseng on morphine-induced dependence and tolerance. We therefore investigated the effect of red ginseng extract (RGE) and biotransformed ginsenosides Rh2, Rg3, and compound K on morphine-induced dependence in mice and rats. Methods: While mice were pretreated with RGE and then morphine was injected intraperitoneally, rats were infused with g...

Monitoring the Evolution of Major Chemical Compound in Dairy Products During Shelf-Life by FTIR

Directory of Open Access Journals (Sweden)

Adriana Păucean

2014-11-01

Full Text Available Fourier-transform infrared (FTIR spectroscopy is considered to be a comprehensive and sensitive method to characterize the chemical composition and for detection of molecular changes in different samples. In this study, FTIRspectroscopy  was employed as an rapid and low-cost technique in order to characterize the FTIR spectra and identify appropriate spectral regions for dairy product fermented by a lactic culture consisting by species of Lactococcus lactis and Leuconostoc mesenteroides. A second objective was to monitore the key chemical compounds (lactose, lactic acid, flavors during fermentation and refrigerated storage (1-21 days, at 4-6°C. By FT-IR fingerprint during fermentation we identified changes of the spectra pattern with specific increasing or decreasing peaks for lactose, lactic acid, esters, aromatic compounds, aminoacids, fatty acids. Also the technique was able to identify chemical compounds involved in the microbial activity such as phosphates and phosphorylated carbohydrates during fermentation and dairy product shelf-life. All the major chemical compounds recorded significant increaments during fermentation and refrigerated storage comparing with the raw milk.

Enhanced Biotransformation of Fluoranthene by Intertidally Derived Cunninghamella elegans under Biofilm-Based and Niche-Mimicking Conditions

Science.gov (United States)

Mitra, Sayani; Pramanik, Arnab; Banerjee, Srijoni; Haldar, Saubhik; Gachhui, Ratan

2013-01-01

The aims of the investigation were to ascertain if surface attachment of Cunninghamella elegans and niche intertidal conditions provided in a bioreactor influenced biotransformation of fluoranthene by C. elegans. A newly designed polymethylmethacrylate (PMMA) conico-cylindrical flask (CCF) holding eight equidistantly spaced rectangular strips mounted radially on a circular disc allowed comparison of fluoranthene biotransformation between CCFs with a hydrophobic surface (PMMA-CCF) and a hydrophilic glass surface (GS-CCF) and a 500-ml Erlenmeyer flask (EF). Fluoranthene biotransformation was higher by 22-fold, biofilm growth was higher by 3-fold, and cytochrome P450 gene expression was higher by 2.1-fold when C. elegans was cultivated with 2% inoculum as biofilm culture in PMMA-CCF compared to planktonic culture in EF. Biotransformation was enhanced by 7-fold with 10% inoculum. The temporal pattern of biofilm progression based on three-channel fluorescence detection by confocal laser scanning microscopy demonstrated well-developed, stable biofilm with greater colocalization of fluoranthene within extracellular polymeric substances and filaments of the biofilm grown on PMMA in contrast to a glass surface. A bioreactor with discs rotating at 2 revolutions per day affording 6-hourly emersion and immersion mimicked the niche intertidal habitat of C. elegans and supported biofilm formation and transformation of fluoranthene. The amount of transformed metabolite was 3.5-fold, biofilm growth was 3-fold, and cytochrome P450 gene expression was 1.9-fold higher in the process mimicking the intertidal conditions than in a submerged process without disc rotation. In the CCF and reactor, where biofilm formation was comparatively greater, higher concentration of exopolysaccharides allowed increased mobilization of fluoranthene within the biofilm with consequential higher gene expression leading to enhanced volumetric productivity. PMID:24038685

A new enantioselective CE method for determination of oxcarbazepine and licarbazepine after fungal biotransformation.

Science.gov (United States)

Bocato, Mariana Zuccherato; Bortoleto, Marcela Armelim; Pupo, Mônica Tallarico; de Oliveira, Anderson Rodrigo Moraes

2014-10-01

The present work describes, for the first time, the simultaneous separation of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-10,11-dihydrocarbamazepine (licarbazepine, Lic) by chiral CE. The developed method was employed to monitor the enantioselective biotransformation of OXC into its active metabolite by fungi. The electrophoretic separations were performed using 10 mmol/L of a Tris-phosphate buffer solution (pH 2.5) containing 1% w/v of β-CD phosphate sodium salt (P-β-CD) as running electrolyte, -20 kV of applied voltage and a 15°C capillary temperature. The method was linear over the concentration range of 1000-30 000 ng/mL for OXC and 75-900 ng/mL for each Lic enantiomer (r ≥ 0.9952). Within-day precision and accuracy evaluated by RSD and relative errors, respectively, were lower than 15% for all analytes. The validated method was used to evaluate the enantioselective biotransformation of OXC, mediated by fungi, into its active metabolite Lic. This study showed that the fungi Glomerella cingulata (VA1) and Beuveria bassiana were able to enantioselectively metabolize the OXC into Lic after 360 h of incubation. Biotransformation by the fungus Beuveria bassiana showed 79% enantiomeric excess for (S)-(+)-Lic, while VA1 gave an enantiomeric excess of 100% for (S)-(+)-Lic. This study opens a new route to the drug (S)-(+)-licarbazepine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systems Biology Approach to Bioremediation of Nitroaromatics: Constraint-Based Analysis of 2,4,6-Trinitrotoluene Biotransformation by Escherichia coli

Directory of Open Access Journals (Sweden)

Maryam Iman

2017-08-01

Full Text Available Microbial remediation of nitroaromatic compounds (NACs is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli has shown remarkable capability for the biotransformation of 2,4,6-trinitro-toluene (TNT. Efforts to develop E. coli as an efficient TNT degrading biocatalyst will benefit from holistic flux-level description of interactions between multiple TNT transforming pathways operating in the strain. To gain such an insight, we extended the genome-scale constraint-based model of E. coli to account for a curated version of major TNT transformation pathways known or evidently hypothesized to be active in E. coli in present of TNT. Using constraint-based analysis (CBA methods, we then performed several series of in silico experiments to elucidate the contribution of these pathways individually or in combination to the E. coli TNT transformation capacity. Results of our analyses were validated by replicating several experimentally observed TNT degradation phenotypes in E. coli cultures. We further used the extended model to explore the influence of process parameters, including aeration regime, TNT concentration, cell density, and carbon source on TNT degradation efficiency. We also conducted an in silico metabolic engineering study to design a series of E. coli mutants capable of degrading TNT at higher yield compared with the wild-type strain. Our study, therefore, extends the application of CBA to bioremediation of nitroaromatics and demonstrates the usefulness of this approach to inform bioremediation research.

Honokiol trimers and dimers via biotransformation catalyzed by Momordica charantia peroxidase: novel and potent α-glucosidase inhibitors.

Science.gov (United States)

He, Ye; Wang, Xiao-Bing; Fan, Bo-Yi; Kong, Ling-Yi

2014-01-15

Ten honokiol oligomers (1-10), including four novel trimers (1-4) and four novel dimers (5-8), were obtained by means of biotransformation of honokiol catalyzed by Momordica charantia peroxidase (MCP) for the first time. Their structures were established on the basis of spectroscopic methods. The biological results demonstrated that most of the oligomers were capable of inhibiting α-glucosidase with significant abilities, which were one to two orders of magnitude more potent than the substrate, honokiol. In particular, compound 2, the honokiol trimer, displayed the greatest inhibitory activity against α-glucosidase with an IC50 value of 1.38μM. Kinetic and CD studies indicated that 2 inhibited α-glucosidase in a reversible, mixed-type manner and caused conformational changes in the secondary structure of the enzyme protein. These findings suggested that 2 might be exploited as a promising drug candidate for the treatment of diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glutathione s-transferase isoenzymes in relation to their role in detoxification of xenobiotics

NARCIS (Netherlands)

Vos, R.M.E.

1989-01-01

The glutathione S-transferases (GST) are a family of isoenzymes serving a major part in the biotransformation of many reactive compounds. The isoenzymes from rat, man and mouse are divided into three classes, alpha, mu and pi, on the basis of similar structural and enzymatic