DESIGNER CELLS FOR ENANTIOSELECTIVE REDUCTION OF KETONES AND USE THEREOF IN EFFICIENT PRODUCTION OF ENANTIOENRICHED ALCOHOLS

摘要

The present invention is to provide a preparation of variant recombinant whole cell biocatalysts, referred herein as “designer cells” having significantly enhanced carbonyl reductase activity for use in the efficient production of variant industrially important enantiomerically enriched alcohols. More specifically, the alcohol is optically pure ethyl (S)-4-chloro-3-hydroxybutyrate, which is useful as chiral building block and an intermediate for the production of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors.

主权项

1. A designer cell that expresses a non-naturally occurring carbonyl reductase polypeptide of sequence selected from SEQ ID NO: 1, 3, 5 or 7 of the Sequence Listing on the surface of cell having 250-fold to 300-fold higher activity per unit mass of CRS polypeptide compared to the designer cell that expresses corresponding carbonyl reductase of SEQ ID NO: 13 or 15 or 17 or 19 of the sequence listing in cytoplasm of cell for conversion of ethyl 4-chloro-3-oxobutyrate of formula 1 to ethyl (S)-4-chloro-3-hydroxybutyrate of formula 2.