Microbial transformation of ibuprofen by a Nocardia species

Abstract

The carboxylic acid functional group of ibuprofen [α-methyl-4-(2- methylpropyl)benzene acetic acid] is reduced to the corresponding alcohol and subsequently esterified to the acetate derivative by cultures of Nocardia species strain NRRL 5646. The alcohol and ester microbial transformation products were isolated, and their structures were determined by 1H and 13C nuclear magnetic resonance spectroscopy and mass spectrometry. By derivatization of synthetic and microbiologically produced ibuprofen alcohols with S(+)-O-acetylmandelic acid, nuclear magnetic resonance analysis indicated that the carboxylic acid reductase of Nocardia sp. is R enantioselective, giving alcohol products with an enantiomeric excess of 61.2%. The R enantioselectivity of the carboxylic acid reductase enzyme system was confirmed by using cell extracts together with ATP and NADPH in the reduction of isomeric ibuprofens.