Zhi-qiang Ren, Yan Liu, Xiaoqiong Pei
Nov 28, 2019
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Influential Citations
2
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Journal
Journal of microbiology and biotechnology
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 putative3-oxoacyl-acyl-carrier-protein reductase, ChKRED12, was able to stereoselectively catalyze the NADPH-dependent reduction to produce (S)-HEES. The reductase activityof ChKRED12 towards other substrates with 3-oxoacyl structure were confirmed with excellent stereoselectivity (>99%ee) 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/LKEES within 12 h, yielding the enantiopure product with >99% ee, showing a remarkable potential to produce(S)-HEES.