Reaction engineering analysis of the asymmetric reduction of ß-ketoesters using recombinant yeast strains

Helge Engelking, doctoral thesis Technische Universität München, 2004

Chiral alcohols as intermediates for the production of optically active pharmaceuticals can easily obtained by microbial reduction of prochiral ketones. In this work a whole cell biotransformation process for the production of two different alcohols has been developed: (S)-4-chloro-3-hydroxybutanoate and ethyl (S)-3-hydroxy-3-phenylpropionate. The first is used as an intermediate for the production of cholesterol-lowering agents and the latter as a building block for antidepressants. Recombinant yeast strains overexpressing a suitable carbonyl reductase as well as a enzyme for the regeneration of cofactors have been used as biocatalysts. By optimising the reaction conditions the enantiomeric excess was improved by 24 % and 8 %, respectively and the yield by 25 % compared to previously reported results. These asymmetric reductions were successfully transferred into the L-scale.


  • Engelking H, Pfaller R, Wich G, Weuster-Botz D (2006): Reaction engineering studies on ß-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae. Enz Microb Technol 38: 536-544.
  • Engelking H, Pfaller R, Wich G, Weuster-Botz D (2004): Stereoselective reduction of ethyl 4-chloro acetoacetate with recombinant Pichia pastoris. Tetrahedron: Asymmetry 15: 3591-3593.