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

A new NADH-dependent carbonyl reductase RhCR 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 RhCR 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.