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 suitable biocatalyst for the asymmetric bioreduction of a ketone (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]. Studies yielded the formulation of a chemically defined cultivation medium that supported excellent growth and bioconversion activity. Process development showed that the optimization of the bioreduction environmental conditions (pH, temperature), the timing of ketone addition, and the implementation of a nutrient feeding strategy were key factors in achieving increased bioreduction rates. The optimized process achieved a 10-fold bioreduction rate improvement over the original process, while reaching final product concentrations of up to 60 g/l. When scaled up in Pilot Plant bioreactors (280 l), the bioreduction process supported the production of several kilograms of highly optically pure (R) alcohol (enantiomeric excess > 98%). (C) 1999 Elsevier Science Inc. All rights reserved.