Asymmetric bioreduction of (2-(4-nitro-phenyl)-N-(2-oxo-2-pyridin-3-yl-ethyl)-acetamide) to its corresponding (R) alcohol [(R)-N-(2-hydroxy-2-pyridin-3-yl-ethyl)-2-(4-nitro-phenyl)-acetamide] by using Candida sorbophila MY 1833

A microbial screen identified the yeast Candida sorbophila MY 1833 as a sui table biocatalyst for the asymmetric bioreduction of a ketone (2-(4-nitro-p henyl)-N-(2-oxo-2-pyridin-3-yl-ethyl)-acetamide) to its corresponding (R) a lcohol [(R) -N-(2-hydroxy-2-pyridin-3-yl-ethyl)-2-(4-nitro-phenyl)-acetamid e]. Studies yielded the formulation of a chemically defined cultivation med ium that supported excellent growth and bioconversion activity. Process dev elopment showed that the optimization of the bioreduction environmental con ditions (pH, temperature), the timing of ketone addition, and the implement ation of a nutrient feeding strategy were key factors in achieving increase d bioreduction rates. The optimized process achieved a 10-fold bioreduction rate improvement over the original process, while reaching final product c oncentrations of up to 60 g/l. When scaled up in Pilot Plant bioreactors (2 80 l), the bioreduction process supported the production of several kilogra ms of highly optically pure (R) alcohol (enantiomeric excess > 98%). (C) 19 99 Elsevier Science Inc. All rights reserved.