This paper is a report on the successful application of bioinformatics to enzyme screening. The synthesis of ethyl (S)-4-chloro-3-hydroxybutanoate (ECHB) by asymmetric reduction of ethyl 4-chloroace-toacetate (ECAA) using fabG-homologues was studied. P-Ketoacyl-acyl carrier protein reductases from both Escherichia coli and Bacillus subtilis, which are components of type 11 fatty acid synthase, could reduce ECAA to (S)-ECHB with 94-98% ee. Furthermore, acetoacetyl-CoA reductases (ARs) from both Ralstonia eutropha and Zoogloea ramigera, whose genes are significantly similar to fabG genes and play a physiological role in the biosynthesis of poly-beta-3-hydroxybutyrate, could also catalyze the asymmetric reduction of ECAA to (S)-ECHB with >99% ee. (S)-ECHB was synthesized to 48.7 g/1 with an optical purity of 99.8% ee, using recombinant E. coli cells coexpressing AR from R. eutropha and glucose dehydrogenase from B. subtilis for the regeneration of NADPH.