Influence of the ethanol and glucose supply rate on the rate and enantioselectivity of 3-oxo ester reduction by baker's yeast

Baker's-yeast-mediated reductions of ketones hold great potential for the i ndustrial production of enantiopure alcohols. In this article we describe t he stoichiometry and kinetics of asymmetric ketone reduction by cell suspen sions of bakers' yeast (Saccharomyces cerevisiae). A system for quantitativ e analysis of 3-oxo ester reduction was developed and allowed construction of full mass and redox balances as well as determination of the influence o f different process parameters on aerobic ketone reduction. The nature of t he electron donor (ethanol or glucose) and its specific consumption rate by the biomass (0-1 mol.kg dw(-1).h(-1)) affected the overall stoichiometry a nd rate of the process and the final enantiomeric excess of the product. Ex cess glucose as the electron donor, i.e. a very high consumption rate of gl ucose, resulted in a high rate of alcoholic fermentation, oxygen consumptio n, and biomass formation and therefore causing low efficiency of glucose ut ilization. Controlled supply of the electron donor at the highest rates app lied prevented alcoholic fermentation but still resulted in biomass formati on and a high oxygen requirement, while low rates resulted in a more effici ent use of the electron donor. Low supply rates of ethanol resulted in biom ass decrease while low supply rates of glucose provided the most efficient strategy for electron donor provision and yielded a high enantiomeric exces s of ethyl (S)-3-hydroxybutanoate. In contrast to batchwise conversions wit h excess glucose as the electron donor, this strategy prevented by-product formation and biomass increase, and resulted in a low oxygen requirement. ( C) 2001 John Wiley & Sons, Inc.