Identification of an epsilon-Keto Ester Reductase for the Efficient Synthesis of an (R)-alpha-Lipoic Acid Precursor

摘要

A novel reductase (CpAR2) with unusually high activity toward an epsilon-keto ester, ethyl 8-chloro-6-oxooctanoate, was isolated from Candida parapsilosis. The asymmetric reduction of ethyl 8-chloro-6-oxooctanoate using Escherichia coli cells coexpressing CpAR2 and glucose dehydrogenase genes gave ethyl (R)-8-chloro-6-hydroxyoctanoate, a key precursor for the synthesis of (R)-alpha-lipoic acid, in high space-time yield (530 g L-1 d(-1)) and with excellent enantiomeric excess (> 99%). This bioprocess was shown to be viable on a 10-L scale. This method provides a greener and more cost-effective method for the industrial production of (R)-alpha- lipoic acid.