文献类型：期刊文献

英文题名：Enantioselective bioreductive preparation of chiral halohydrins employing two newly identified stereocomplementary reductases

作者：Xu, Guo-Chao[1,2,3];Yu, Hui-Lei[1,2];Shang, Yue-Peng[1,2];Xu, Jian-He[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai 200237, Peoples R China;[3]Jiangnan Univ, Sch Biotechnol, Key Lab Ind Biotechnol, Minist Educ, Wuxi 214122, Peoples R China

年份：2015

卷号：5

期号：29

起止页码：22703

外文期刊名：RSC ADVANCES

收录：;EI(收录号：20151100619607);WOS:【SCI-EXPANDED(收录号:WOS:000350643700050)】；

基金：This work was financially supported by the National Natural Science Foundation of China (no. 21276082), Ministry of Science and Technology, P.R. China (nos 2011CB710800 and 2011AA02A210), China National Special Fund for State Key Laboratory of Bioreactor Engineering (no. 2060204) and Huo Yingdong Education Foundation.

语种：英文

外文关键词：Enzyme activity - Ketones

摘要：Two robust stereocomplementary carbonyl reductases (DhCR and CgCR) were identified through rescreening the carbonyl reductase toolbox. Five reductases were returned through the activity and enantioselectivity assay for alpha-chloro-1-acetophenone and ethyl 4-chloro-3-oxo-butanate (COBE). Three reductases were stable at elevated substrate loading. Enzymatic characterization revealed that DhCR and CgCR were more thermostable. As much as 330 g COBE in 1 L biphasic reaction mixture was reduced to (S)-and (R)-3-hydroxy-4-chlorobutyrate by DhCR and CgCR (coexpressed with glucose dehydrogenase), with 92.5% and 93.0% yields, >99% ee, and total turnover numbers of 53 800 and 108 000, respectively. Six other alpha-halohydrins were asymmetrically reduced to optically pure forms at a substrate loading of 100 g L-1. Our results indicate the potential of these two stereocomplementary reductases in the synthesis of valuable alpha-halohydrins for pharmaceuticals.