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 |
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| Authors: | Zhi‐Qiang Liu Zhong‐Liang Hu Xiao‐Jian Zhang Xiao‐Ling Tang Feng Cheng Ya‐Ping Xue Ya‐Jun Wang Lin Wu Dan‐Kai Yao Yi‐Teng Zhou Yu‐Guo Zheng |
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| Institution: | Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, P.R. China |
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| Abstract: | 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 |
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| Keywords: | carbonyl reductase tert‐butyl (S)‐6‐chloro‐5‐hydroxy‐3‐oxohexanoate tert‐butyl (3R 5S)‐6‐chloro‐3 5‐dihydroxyhexanoate asymmetric reduction space‐time yield |
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