Asymmetric Synthesis of Ethyl (<i>R</i>)-4-Chloro-3-Hydroxybutanoate with a Two Recombinant <i>Escherichia coli</i> System

Abstract

The asymmetric reduction of ethyl 4-chloro-acetoacetate (CAAE) to ethyl (R)-4-chloro-3- hydroxybutanoate (R-CHBE) biocatalysed by the aldehyde reductase of Sporobolomyces salmonicolor expressed in E. coli M15 (pQE30-alr) in combination with regeneration of NADPH by the glucose dehydrogenase of Bacillus megaterium expressed in E. coli M15 (pQE30-gdh) was reported. The bioreduction was carried out in a two-phase reaction system with n-butyl acetate as an organic solvent. Bioconversion of 300 mmol CAAE with a final yield of 97.5 % and an enantiometric excess of 99 % was achieved without the addition of cofactor NADPH.