Chiral alcohol synthesis with yeast carbonyl reductases

Synthesis of chiral alcohols, (R)- and (S)-4-chloro-3-hydroxybutanoate ethyl esters (CHBE), was performed through the enzymatic asymmetric reduction of 4-chloroacetoacetate ethyl ester (CAAE). The enzymes reducing CAAE to (R)- and (S)-CHBE were found to be produced by Sporobolomyces salmonicolor and Candida magnoliae, respectively. The enzyme of S, salmonicolor is a novel NADPH-dependent aldehyde reductase (AR) belonging to the aldo-keto reductase superfamily. The C. magnoliae enzyme also seems to be a novel NADPH-dependent carbonyl reductase. When AR-overproducing Escherichia coli transformant cells or C. magnoliae cells were incubated in an organic solvent-water two-phase system, 300 or 90 mg/ml of CAAE was almost stoichiometrically converted to (R)- or (S)-CHBE (> 92% e.e.), respectively. (C) 1998 Elsevier Science B.V. All rights reserved.