Improvement of (R)-carbonyl reductase-mediated biosynthesis of (R)-1-phenyl-1,2-ethanediol by a novel dual-cosubstrate-coupled system for NADH recycling

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• 作者：Shanshan Wang^a ; Yan Xu^a ; ^{yxu@jiangnan.edu.cn} ; Rongzhen Zhang^a ; Botao Zhang^a ; Rong Xiao^b
• 关键词：RCR ; (R)-carbonyl reductase ; (R)-PED ; (R)-1-phenyl-1 ; 2-ethanediol ; 2-HAP ; 2-hydroxyacetophenone ; ADH ; alcohol dehydrogenase ; PMS ; phenazine ethosulfate ; MTT ; 3-(4 ; 5-dimethylthiazolyl-2)-25-diphenyltetrazolium bromide
• 刊名：Process Biochemistry
• 出版年：2012
• 期刊代码：29_13595113
• 类别：bio
• 出版时间：July, 2012
• 卷：47
• 期：7
• 页码：1060-1065
• 文件大小：579 K

摘要

An NAD(H)-dependent (R)-carbonyl reductase (RCR) from Candida parapsilosis catalyzes the asymmetric reduction of 2-hydroxyacetophenone (2-HAP) to (R)-1-phenyl-1,2-ethanediol ((R)-PED), which is a valuable chiral building block in the pharmaceutical and fine chemical industries. Biosynthesis efficiency of (R)-PED was considerably improved by a novel dual-cosubstrate-coupled system. By simultaneously employing isopropanol (10%, v v^鈭?) and glycerol (8%, v v^鈭?) as sacrificial cosubstrates, the (R)-PED product had an excellent optical purity of >99.9%and a conversion of 85.5%, which were nearly 2- and 11-fold higher than those without adding cosubstrate, respectively. Besides, the productivity was dramatically enhanced from 0.02 g L^鈭? h^鈭? to 5 g L^鈭? h^鈭?, and the maximum acceptable concentration of 2-HAP was elevated to 10 g L^鈭?. Isopropanol was directly oxidized by RCR in the formation of NADH, while glycerol was metabolized by cellular enzymes to release NADH. Moreover, glycerol prevented cells from losing viability and alleviated the toxicity of isopropanol and acetone for cells. Interestingly, there was a cooperative interaction between isopropanol and glycerol for the improvement of biosynthesis efficiency of (R)-PED.