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KMID : 0545120190290111769
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Journal of Microbiology and Biotechnology
2019 Volume.29 No. 11 p.1769 ~ p.1776
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Stereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl) propanoateusing theshort-chain dehydrogenase/reductaseChKRED12
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Ren Zhi-Qiang
Liu Yan
Pei Xiao-Qiong
Wu Zhong-Liu
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Abstract
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Ethyl (S)-3-hydroxy-3-(2-thienyl)propanoate((S)-HEES)acts as a key chiral intermediate for the blockbuster antidepressant drug duloxetine, which canbe achieved viathe stereoselective bioreduction ofethyl 3-oxo-3-(2-thienyl) propanoate (KEES) that containsa 3-oxoacyl structure.The sequences of the short-chain dehydrogenase/reductases from Chryseobacteriumsp. CA49 were analyzed, and the putative3-oxoacyl-acyl-carrier-protein reductase, ChKRED12, was able to stereoselectivelycatalyze theNADPH-dependent reduction to produce(S)-HEES.The reductase activityof ChKRED12towardsothersubstrates with 3-oxoacyl structurewereconfirmed with excellent stereoselectivity (>99%ee) in most cases.When coupled with a cofactor recycling systemusingglucose dehydrogenase, the ChKRED12was able to catalyze the complete conversion of 100 g/LKEES within 12h, yielding the enantiopure product with>99% ee, showing a remarkablepotential to produce(S)-HEES.
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KEYWORD
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Bioreduction, 3-oxoacyl-acyl-carrier-protein reductase, Short chain dehydrogenase, Duloxetine
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