Microbial Resolution of α-Hydroxy Acids by Enantiospecifically Dehydrogenating Bacteria from Soil

Abstract

Thirty-three bacterial strains were isolated from soil, utilizing optically asymmetric degradation of dl -2-hydroxy-4-methylpentanoic acid ( dl -HMPA) as the screening probe. Those strains were distributed in the following group and genera: Coryneform and Bacillus, Pseudomonas, and Streptomyces. Among them, the most potent strains, Bacillus freudenreichii NRS-137KH20B and Brevibacterium albidum NRS-130KH20B, could perform the resolution of more than 30 g of dl -HMPA per liter within 4 to 5 days of fermentation. Optically pure l - and d -HMPA enantiomers were obtained in more than 80% theoretical yield, whereas the transformed enantiomer was almost quantitatively recovered as 2-oxo-4-methyl-pentanoic acid in the culture broth. The enantiospecific dehydrogenation responsible for this resolution reaction had a rather wide substrate specificity on straight or branched aliphatic C 4 to C 16 2-hydroxy acids, exhibiting the optima at chain lengths of either C 7 or C 5 , although the enantiospecificity was not changed by chain length. The process was thus successfully extended to the preparation of optically pure C 5 to C 9 2-hydroxy acids.