Stereoselective reduction of ethyl 2-methyl-3-oxobutanoate by bacteria

More than 450 bacterial strains were examined for their ability to reduce ethyl 2-methyl-3-oxobutanoate (1) to ethyl 3-hydroxy-2-methylbutanoate. Nine strains of enteric bacteria were found to predominantly yield the product with a syn configuration. Of these strains, five gave ethyl (2R,3S) 3-hydroxy-2-methylbutanoate (2a) with more than 98% diastereoisomeric excess (d,e,) and over 99% enantiomeric excess (e,e,) Klebsiella pneumoniae IFO 3319 was found to give the highest d.e., f.e., and chemical yield at a high concentration of 1. Reduction of 1 was then done with the bacterium in a 200-liter fermentor. Two kilograms of 1 was converted to 2a with 99% d.e., >99% e.e., and 99% chemical yield.