Microbial metabolism of 2-arylpropionic acids: effect of environment on the metabolism of ibuprofen by Verticillium lecanii

The effect of environment on the growth of Verticillium lecanii and its metabolic transformation of racemic ibuprofen are reported. The growth of V. lecanii exhibited a lag phase of up to 12 h followed by a period of rapid growth for up to 4 d. The optimal conditions for growth of the micro-organism were determined to be 24 degrees C at pH 7.0 with a culture volume of up to one-tenth of the culture flask volume. The metabolic oxidation of(R,S)-ibuprofen occurred in both growing cultures and washed cell suspensions of V. lecanii. Examination of the stereochemical composition of the remaining substrate indicated that under both conditions the oxidation was substrate stereoselective for the R-enantiomer of the drug. Using growing cultures of the micro-organism, quantitative conversion of the substrate to the metabolite was achieved following incubation for 14 d. Examination of the enantiomeric composition of the metabolic product indicated an excess of the S-isomer (ratio S/R = 2.1). The possible mechanisms for the apparent anomaly in the stereoselectivity of(R,S)-ibuprofen metabolism and the enantiomeric composition of the metabolite are discussed.