Efficient bioreduction of bicyclo[2.2.2]octane-2,5-dione and bicyclo[2.2.2]oct-7-ene-2,5-dione by genetically engineered Saccharomyces cerevisiae

A screening of non-conventional yeast species and several Saccharomyces cerevisiae ( baker's yeast) strains overexpressing known carbonyl reductases revealed the S. cerevisiae reductase encoded by YMR226c as highly efficient for the reduction of the diketones 1 and 2 to their corresponding hydroxyketones 3 - 6 ( Scheme 1) in excellent enantiomeric excesses. Bioreduction of 1 using the genetically engineered yeast TMB4100, overexpressing YMR226c, resulted in > 99% ee for hydroxyketone (+)- 4 and 84 - 98% ee for (-)- 3, depending on the degree of conversion. Baker's yeast reduction of diketone 2 resulted in > 98% ee for the hydroxyketones (+)- 5 and (+)- 6. However, TMB4100 led to significantly higher conversion rates ( over 40 fold faster) and also a minor improvement of the enantiomeric excesses (> 99%).