Identification of an ε‐Keto Ester Reductase for the Efficient Synthesis of an ( R )‐α‐Lipoic Acid Precursor

A novel reductase ( Cp AR2) with unusually high activity toward an ε‐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 Cp AR2 and glucose dehydrogenase genes gave ethyl ( R )‐8‐chloro‐6‐hydroxyoctanoate, a key precursor for the synthesis of ( R )‐α‐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 )‐α‐lipoic acid.