• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.3
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• pp.167-179
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• 2005

Chiral epoxides are highly valuable intermediates, used for the synthesis of pharmaceutical drugs and agrochemicals. They have broad scope of market demand because of their applications. A major challenge in modern organic chemistry is to generate such compounds in high yields, with high stereo- and regio-selectivities. Epoxide hydrolases (EH) are promising biocatalysts for the preparation of chiral epoxides and vicinal diols. They exhibit high enantioselectivity for their substrates, and can be effectively used in the resolution of racemic epoxides through enantioselective hydrolysis. The selective hydrolysis of a racemic epoxide can produce both the corresponding diols and the unreacted epoxides with high enantiomeric excess (ee) value. The potential of microbial EH to produce chiral epoxides and vicinal diol has prompted researchers to explore their use in the synthesis of epoxides and diols with high ee values.

• Environmental Mutagens and Carcinogens
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• v.17 no.2
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• pp.97-108
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• 1997

The drugs or xenobiotics introduced to the body, are detoxified through the process of biotransformation in the body. In this process, most of the insoluble compounds become more polar, soluble and easily excretable. But, parts of introduced materials are metabolized to highly reactive electrophilic carcinogens through activation pathways. These metabolites are toxic and can react with DNA, RNA and proteins which are nucleophilic compounds. The objective of this study is to illustrate the aleactivation pathways of two highly reactive epoxide compounds, vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO). They are the ultimate electrophilic carcinogens of ethyl carbamate(urethane) and 4-nitrophenyl vinyl ether, respectively. In this research, we studied the inhibition of the mutagenic activities of VCO or NPO by nuchieophiles [glutahione(GSH) and N-acetylcysteine(NAC)], detoxifying enzymes[epoxide hydrolase and glutathione-S-transferase(GST)] and intracellular organelles (microsomes and cytosol). In addition we also tested the suppression of DNA adducts formation by GSH and NAC. The results are summerized as follow. 1. The microsomes and cytosol which contain epoxide hydrolase and GST, respectively, decreased the mutagenicity of VCO (74% and 95%, respecfivel), and NPO (35% and 93%, respectively). The nucleophilic GSH and NAC decreased the mutagenicity by 86% (VCO) and 80% (NPO), 76% (VCO) and 40% (NPO), respectively. 2. The purified epoxide hydrolase decreased the mutagenicity of two epoxides in a dose-dependent manner, and GSH also decreased the mutagenicity in the presence of GST. 3. Formation of two DNA adducts, 7-(2'-oxoethyi)guanine (OEG) and N2,3-ethenoguanine(EG), were compared in the presence of calf thymus DNA and epoxide (VCO or NPO) in vitro system. The amounts of DNA adducts were decreased in the presence of GSH (25% and 29% in VCO, 32% and 29% in NPO), and NAC (14% and 16% in VCO, 21% and 11% in NPO), respectively. From these results, it is concluded that the ultimate carcinogenic metabolites, VCO and NPO, can be made in the body, but much of them may be inactivated and detoxified by the nucleophilic GSH, NAC and detoxifying enzymes (epoxide hydrolase and GST). Therefore, by these mechanism, the formation of DNA adducts and mutagenic activities of these two epoxides may be lowered in vivo.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.648-651
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• 2001

Kinetic resolution of various racemic aromatic epoxides by newly isolated Aspergillus niger LK has been investigated, and enantioselectivity of whole-cell biocatalyst was analyzed. The epoxide hydrolase (EHase) of A. niger LK was cloned using RT-PCR. The sequence homology was compared with that of other microbial EHase and the gene for EHase was characterized at molecular level.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.177-177
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• 2002

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.63.1-63.1
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• 2007

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• Applied Chemistry for Engineering
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• v.19 no.5
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• pp.491-496
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• 2008

The microsomal epoxide hydrolase gene (referred to as mMCEH) of Mugil cephalus was cloned by PCR, and then inserted to pColdI and pET-21b(+) vector, respectively. The recombinant E. coli possessing the recombinant plasmids exhibited the enantioperference toward (R)-styrene oxide. When enantioselective kinetic resolutions were conducted with 20 mM racemic styrene oxide, enantiopure (S)-styrene oxide was obtained with high enantiopurity more than 99% enantiomeric excess (ee) and 24.50% yield by using the recombinant E. coli harboring pET-21b(+)/mMCEH.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.233-241
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• 1996

Previous studies have shown that glucocorticoid suppresses microsomal epoxide hydrolase(EH) gene expression and that EH expression is altered during pregnancy. The effects of progesterone on the expression of rat EH and certain glutathione S-transferase(GST) genes were examined in this study. Northern RNA blot analysis revealed that progesterone was effective in increasing hepatic EH mRNA levels at 12 h to 48 h after treatment with a maximal 9-fold increase being noted at 12 h time point. Nonetheless, multiple daily treatment with progesterone rather caused minimal relative increases in EH mRNA levels. GST Ya and Yb1/2 mRNA levels were also transiently elevated at 12 h after progesterone treatment, followed by gradual decreases from the maximal Increases at day 1, 2 and 5 post-treatment. These changes in EH and GST mRNA levels were noted only at a relatively high dose of progesterone. Furthermore, immunoblot analyses showed that rats treated with progesterone for 5 days failed to show EH or GST induction, indicating that progesterone-induced alterations in EH and GST mRNA levels do not reflect bona fide induction of the detoxifying enzymes. Concomitant progesterone treatment of rats with the known EH inducers including ketoconazole and clotrimazole failed to additively nor antagonistically alter EH mRNA levels. In contrast, dexamethasone substantially reduced ketoconazole- or clotrimazole-inducible EH expression. These results showed that progesterone stimulates the EH, GST Ya and Yb1/2 gene expression at early times followed by marked reduction in the RNA levels from the maximum after multiple treatment and that the changes in mRNA do not necessarily reflect induction of the proteins.

• Korean Journal of Environmental Agriculture
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• v.34 no.3
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• pp.244-251
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• 2015

BACKGROUND: Recent studies have described the importance of bacteria that can degrade polycyclic aromatic hydrocarbons (PAHs). Here we screened bacterial isolates from commercial gasoline for PAH degraders and characterized their ability to degrade PAHs, lipids and proteins as well as their enantioselective epoxide hydrolase activity, salt tolerance, and seawater survival. METHODS AND RESULTS: One hundred two bacteria isolates from commercial gasoline were screened for PAH degraders by adding selected PAHs on to the surface of agar plates by the sublimation method. A clear zone was found only around the colonies of PAH degraders, which accounted for 13 isolates. These were identified as belonging to Bacillus sp., Brevibacterium sp., Micrococcus sp., Corynebacterium sp., Arthrobacter sp., and Gordonia sp. based on 16S rRNA sequences. Six isolates belonging to Corynebacterium sp., 3 of Micrococcus sp., Arthrobacter sp. S49, and Gordonia sp. H37 were lipid degraders. Arthrobacter sp. S49 was the only isolate showing high proteolytic activity. Among the PAH-degrading bacteria, Arthrobacter sp. S49, Brevibacterium sp. S47, Corynebacterium sp. SK20, and Gordonia sp. H37 showed enantioselective epoxide hydrolase activity with biocatalytic resolution of racemic styrene oxide. Among these, highest enantioselective hydrolysis activity was seen in Gordonia sp. H37. An intrinsic resistance to kanamycin was observed in most of the isolates and Corynebacterium sp. SK20 showed resistance to additional antibiotics such as tetracycline, ampicillin, and penicillin. CONCLUSION: Of the 13 PAH-degraders isolated from commercial gasoline, Arthrobacter sp. S49 showed the highest lipid and protein degrading activity along with high active epoxide hydrolase activity, which was the highest in Gordonia sp. H37. Our results suggest that bacteria from commercial gasoline may have the potential to degrade PAHs, lipids, and proteins, and may possess enantioselective epoxide hydrolase activity, high salt tolerance, and growth potential in seawater.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.772-778
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• 2005

Chiral epoxides are important chiral synthons in organic synthesis for the production of chiral pharmaceuticals and functional food additives. Chiral epoxides can be synthesized by enantioselective introduction of oxygen to double bond of substrate by monooxygenase. Peroxidase also carry out asymmetric epoxidation of alkene in the presence of hydrogen peroxide. Kinetic resolution of racemic epoxides via enantioselective hydrolysis reaction by epoxide hydrolase (EH) is a very promising method since chiral epoxides with a high optical purity can be obtained from cheap and readily available racemic epoxides. In this review, various biocatalytic approaches for the production of chiral epoxides with several examples are presented and their commercial potential is discussed.

• Korean Journal of Pharmacognosy
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• v.28 no.4
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• pp.239-246
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• 1997

The methanol extracts of some marine algae were tested for investigating the effects on the formation of lipid peroxide and the activities of free radical generating enzyme in vitro in bromobenzene-treated rat. The extracts of Enteromorpha compressa, Capsosiphon fulvescens, Gelidium amansii, Hizikia fusiformis, Sargassum siliquastrum and Sargassum thunbergii which decreased the formation of lipid peroxide, inhibited the activity of xanthine and aldehyde oxidases by adding of each extracts. Phloroglucinol isolated from Ecklonia stolonifera reduced bromobenzene-induced hepatic lipid peroxidation. This compound administered daily over one week before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase and glu tathione S-transferase. Epoxide hydrolase activity was decreased by bromobenzene, which was restored by pretreatment of phloroglucinol, The results suggest that the bromobenzene-induced hepatic lipid peroxidation by phloroglucinol is reduced by enhancing the activity of epoxide hydrolase.