Kinetic resolution of racemic 5,6-epoxy-bicyclo[2.2.1]heptane-2-one using genetically engineered Saccharomyces cerevisiae

(+)-5,6-Epoxy-bicyclo2.2.1]heptane-2-one, (+)-1, and endo-(−)-5,6-epoxy-bicyclo2.2.1]heptane-2-ol, endo-(−)-2, were obtained by kinetic resolution of rac-1 by asymmetric bioreduction catalyzed by whole cells of a genetically engineered Saccharomyces cerevisiae yeast strain. The strain, TMB4100, had 1% phosphoglucose isomerase (PGI) activity and overexpressed a specific short-chain dehydrogenase, encoded by the gene YMR226c. The whole cell biocatalyst was demonstrated to be significantly inactivated within 24 h, thus restricting the reaction to low concentration. Despite this, the resolution method could be used to produce optically pure (+)-1 and endo-(−)-2 from the racemic mixture at 5 g/L substrate. At optimal conditions, 1 g of rac-1 was kinetically resolved to give (+)-1 in 95% ee and 28% yield and endo-(−)-2 in 74% ee, 80% de and 45% yield.