文献类型：期刊文献

英文题名：Efficient Synthesis of (R)-2-Chloro-1-(2,4-dichlorophenyl)ethanol with a Ketoreductase from Scheffersomyces stipitis CBS 6045

作者：Shang, Yue-Peng[1];Chen, Qi[1];Kong, Xu-Dong[1];Zhang, Yu-Jun[1];Xu, Jian-He[1];Yu, Hui-Lei[1]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2017

卷号：359

期号：3

起止页码：426

外文期刊名：ADVANCED SYNTHESIS & CATALYSIS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000394586400009)】；

基金：This work was financially supported by the National Natural Science Foundation of China (No. 21672063 & 21536004), the Fundamental Research Funds for the Central Universities (No. 222201514039), Shanghai Science and Technology Program (No. 15JC1400403) and SKLBE (No. 2060204). We thank Prof. Jia- Hai Zhou for his kind advice on crystal data analyses. We are grateful for access to beamline BL17U1 at Shanghai Synchrotron Radiation Facility and thank the beamline staff for technical support.

语种：英文

外文关键词：biocatalysis; bioreduction; (R)-2-chloro-1-(2,4-dichlorophenyl) ethanol; cofactor recycle; reductase

摘要：By enzyme screening, a ketoreductase cloned from Scheffersomyces stipitis CBS 6045 and named SsCR was identified that could catalyze the asymmetric hydrogenation of a variety of aromatic ketones. SsCR exhibited a specific activity of 65 Umg(-1) protein and excellent enantioselectivity (99.9% ee) towards the hydrophobic substrate 2-chloro- 1-(2,4-dichlorophenyl) ethanone, which is an intermediate in the synthesis of common antifungal agents such as miconazole, econazole and sertaconazole. The kinetic parameter k(cat)/K-m was 4.51 X 10(3) s(-1)mM(-1), showing the great catalytic efficiency of SsCR towards this substrate. Molecular dynamic simulation results shed light on the higher substrate binding free energy change for this substrate relative to other substrates. Based on the good catalytic properties of SsCR, (R)-2-chloro-1-(2,4-dichlorophenyl) ethanol could be obtained with a space-time yield (STY) of up to 268 gL(-1)d(-1) without any additional cofactor required in the reductive reaction process. On scaling up the bioreaction, the (R)-alcohol was isolated with 88.2% yield and 99.9% ee. The environmental factor (E factor) of this reaction was 7.25 when process water was excluded.