1. Stereoselective Bioreduction of Ethyl 3-Oxo-3-(2-Thienyl) Propanoate Using the Short-Chain Dehydrogenase/Reductase Ch KRED12.
- Author
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Ren ZQ, Liu Y, Pei XQ, and Wu ZL
- Subjects
- 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase chemistry, 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase genetics, Amino Acid Sequence, Bacterial Proteins chemistry, Bacterial Proteins genetics, Catalysis, Chryseobacterium enzymology, Chryseobacterium genetics, Escherichia coli genetics, Escherichia coli metabolism, Glucose 1-Dehydrogenase metabolism, Kinetics, Oxidation-Reduction, Propionates chemistry, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Short Chain Dehydrogenase-Reductases chemistry, Short Chain Dehydrogenase-Reductases genetics, Stereoisomerism, Substrate Specificity, 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase metabolism, Bacterial Proteins metabolism, Propionates metabolism, Short Chain Dehydrogenase-Reductases metabolism
- Abstract
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 Chryseobacterium sp. CA49 were analyzed, and the putative3-oxoacyl-acyl-carrier-protein reductase, Ch KRED12, was able to stereoselectivelycatalyze theNADPH-dependent reduction to produce ( S )-HEES.The reductase activity of Ch KRED12 towardsothersubstrates 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 Ch KRED12 was able to catalyze the complete conversion of 100 g/l KEES within 12h, yielding the enantiopure product with >99% ee, showing a remarkable potential to produce ( S )-HEES.
- Published
- 2019
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