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http://dx.doi.org/10.4014/jmb.1805.04058

Stereoselective Bioreduction of Ethyl 3-Oxo-3-(2-Thienyl) Propanoate Using the Short-Chain Dehydrogenase/Reductase ChKRED12  

Ren, Zhi-Qiang (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences)
Liu, Yan (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences)
Pei, Xiao-Qiong (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences)
Wu, Zhong-Liu (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences)
Publication Information
Journal of Microbiology and Biotechnology / v.29, no.11, 2019 , pp. 1769-1776 More about this Journal
Abstract
Ethyl (S)-3-hydroxy-3-(2-thienyl) propanoate ((S)-HEES) acts as a key chiral intermediate for the blockbuster antidepressant drug duloxetine, which can be achieved via the stereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl) propanoate (KEES) that contains a 3-oxoacyl structure. The sequences of the short-chain dehydrogenase/reductases from Chryseobacterium sp. CA49 were analyzed, and the putative 3-oxoacyl-acyl-carrier-protein reductase, ChKRED12, was able to stereoselectively catalyze the NADPH-dependent reduction to produce (S)-HEES. The reductase activity of ChKRED12 towards other substrates with 3-oxoacyl structure were confirmed with excellent stereoselectivity (>99% enantiomeric excess) in most cases. When coupled with a cofactor recycling system using glucose dehydrogenase, the ChKRED12 was able to catalyze the complete conversion of 100 g/l KEES within 12 h, yielding the enantiopure product with >99% ee, showing a remarkable potential to produce (S)-HEES.
Keywords
Bioreduction; 3-oxoacyl-acyl-carrier-protein reductase; short-chain dehydrogenase; duloxetine;
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