Efficient synthesis of an ε-hydroxy ester in a space–time yield of 1580 g L−1 d−1 by a newly identified reductase RhCR

A new NADH-dependent carbonyl reductase Rh CR capable of efficiently reducing the ε-ketoester ethyl 8-chloro-6-oxooctanoate (ECOO) to give ethyl ( S )-8-chloro-6-hydroxyoctanoate [( S )-ECHO], an important chiral precursor for the synthesis of ( R )-α-lipoic acid, was identified from Rhodococcus sp. ECU1014. Using recombinant Escherichia coli cells expressing Rh CR and glucose dehydrogenase used for the regeneration of cofactor, 440   g L −1 (2   M) of ECOO were stoichiometrically converted to ( S )-ECHO in a space–time yield of 1580   g   L −1   d −1 without the external addition of any expensive cofactor.