Drug metabolism in microorganisms.

Several wild type and recombinant microorganisms can transform drugs to the equivalent human metabolites. Fungi, such as Cunninghamella spp., and Streptomyces bacteria express cytochrome P450 (CYP) enzymes that enable analogous phase I (oxidative) reactions with a wide range of drugs. The gene encoding the bifunctional CYP102A1 in Bacillus megaterium can be expressed easily in E. coli, and extensive mutagenesis experiments have generated numerous variants that can produce human drug metabolites. Additionally, human CYP isoforms have been expressed in various hosts. The application of microbial CYPs to the production of human drug metabolites is reviewed, and additional applications in the field of drug development are considered.