Biotransformation of warfarin by the fungus Beauveria bassiana

Abstract

Biotransformation of racemic warfarin by the fungus Beauveria bassiana IMI 12939 was studied as part of an investigation into alternative methods for the production of drug metabolites. Resting cell suspensions in buffer were able to biotransform warfarin. High activity occurred within a broad pH range (6.0-9.0) with an optimum at 7.0. The major metabolites were 4'-hydroxywarfarin (metabolite I), warfarin alphadiketone (metabolite B) and diastereomers of novel tautomeric ring-cleaved warfarin (metabolites E and F). The exact quantitative metabolite profile obtained following warfarin metabolism was shown to be highly dependent upon the cell concentration. Kinetic evidence suggested the operation of multiple enzyme activities.