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Large‐scale synthesis of tert‐ butyl ( 3R,5S )‐6‐chloro‐3,5‐dihydroxyhexanoate by a stereoselective carbonyl reductase with high substrate concentration and product yield
Author(s) -
Liu ZhiQiang,
Hu ZhongLiang,
Zhang XiaoJian,
Tang XiaoLing,
Cheng Feng,
Xue YaPing,
Wang YaJun,
Wu Lin,
Yao DanKai,
Zhou YiTeng,
Zheng YuGuo
Publication year - 2017
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.2460
Subject(s) - stereoselectivity , yield (engineering) , substrate (aquarium) , chemistry , reductase , stereochemistry , organic chemistry , medicinal chemistry , enzyme , catalysis , physics , biology , thermodynamics , ecology
To biosynthesize the (3R,5S)‐CDHH in an industrial scale, a newly synthesized stereoselective short chain carbonyl reductase (SCR) was successfully cloned and expressed in Escherichia coli. The fermentation of recombinant E. coli harboring SCR was carried out in 500 L and 5000 L fermenters, with biomass and specific activity of 9.7 g DCW/L, 15749.95 U/g DCW, and 10.97 g DCW/L, 19210.12 U/g DCW, respectively. The recombinant SCR was successfully applied for efficient production of (3R,5S)‐CDHH. The scale‐up synthesis of (3R,5S)‐CDHH was performed in 5000 L bioreactor with 400 g/L of (S)‐CHOH at 30°C, resulting in a space‐time yield of 13.7 mM/h/g DCW, which was the highest ever reported. After isolation and purification, the yield and d.e. of (3R,5S)‐CDHH reached 97.5% and 99.5%, respectively. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:612–620, 2017