Stereospecific Reduction of Methyl o-Chlorobenzoylformate at 300 g center dot L-1 without Additional Cofactor using a Carbonyl Reductase Mined from Candida glabrata
文献类型：期刊论文
| 作者 | Ma, Hongmin1; Yang, Linlin2; Ni, Yan1; Zhang, Jie1; Li, Chun-Xiu1; Zheng, Gao-Wei1; Yang, Huaiyu2; Xu, Jian-He1 |
| 刊名 | ADVANCED SYNTHESIS & CATALYSIS
 |
| 出版日期 | 2012-06 |
| 卷号 | 354期号:9页码:1765-1772 |
| 关键词 | bioinformatics biotransformations cofactors oxidoreductases |
| ISSN号 | 1615-4150 |
| DOI | 10.1002/adsc.201100366 |
| 文献子类 | Article |
| 英文摘要 | In order to search for oxidoreductases suitable for the preparation of methyl (R)-o-chloromandelate [(R)-CMM], the key intermediate for clopidogrel, the homologous proteins of Gre2p were expressed in Escherichia coli, among which CgKR1 showed the most satisfactory activity and stereoselectivity towards methyl o-chlorobenzoylformate (CBFM). Using the crude enzyme of CgKR1 and glucose dehydrogenase (GDH), as much as 300 g center dot L-1 of CBFM was almost stoichiometrically converted to (R)-CMM with excellent enantiomeric excess (98.7% ee). More importantly, the reaction could be performed without external addition of an expensive cofactor. The substrate profile indicates that keto esters serve as the most suitable substrate, which was confirmed by gram-scale preparations. Homology modeling and docking analysis revealed the molecular basis for the high stereoselectivity of CgKR1. These demonstrate not only the feasibility of in silico mining of novel enzymes based on sequence homology but also the applicability of this new reductase for the practical production of optically active (R)-CMM. |
| WOS关键词 | RECOMBINANT ESCHERICHIA-COLI ; BROAD SUBSTRATE-SPECIFICITY ; ASYMMETRIC REDUCTION ; EFFICIENT SYNTHESIS ; BAKERS-YEAST ; STEREOSELECTIVE REDUCTION ; HIGH ENANTIOSELECTIVITY ; BIOCATALYTIC REDUCTION ; STEREOCHEMICAL CONTROL ; ALCOHOL-DEHYDROGENASE |
| 资助项目 | National Natural Science Foundation of China[20902023] ; National Natural Science Foundation of China[31071604] ; Ministry of Science and Technology, P. R. China[2009CB724706] ; Ministry of Science and Technology, P. R. China[2011CB710800] ; China National Special Fund for State Key Laboratory of Bioreactor Engineering[2060204] ; Shanghai Leading Academic Discipline Project[B505] ; Shanghai Committee of Science and Technology[11431921600] ; Shanghai Municipal Education Commission[11CXY24] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000305209300021 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278051]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Yang, Huaiyu |
| 作者单位 | 1.E China Univ Sci & Technol, Lab Biocatalysis & Synthet Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Hongmin,Yang, Linlin,Ni, Yan,et al. Stereospecific Reduction of Methyl o-Chlorobenzoylformate at 300 g center dot L-1 without Additional Cofactor using a Carbonyl Reductase Mined from Candida glabrata[J]. ADVANCED SYNTHESIS & CATALYSIS,2012,354(9):1765-1772. |
| APA | Ma, Hongmin.,Yang, Linlin.,Ni, Yan.,Zhang, Jie.,Li, Chun-Xiu.,...&Xu, Jian-He.(2012).Stereospecific Reduction of Methyl o-Chlorobenzoylformate at 300 g center dot L-1 without Additional Cofactor using a Carbonyl Reductase Mined from Candida glabrata.ADVANCED SYNTHESIS & CATALYSIS,354(9),1765-1772. |
| MLA | Ma, Hongmin,et al."Stereospecific Reduction of Methyl o-Chlorobenzoylformate at 300 g center dot L-1 without Additional Cofactor using a Carbonyl Reductase Mined from Candida glabrata".ADVANCED SYNTHESIS & CATALYSIS 354.9(2012):1765-1772. |
入库方式： OAI收割
来源：上海药物研究所
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