Cytochrome P450 Enzymes for the Synthesis of Novel and Known Drugs and Drug Metabolites

This chapter provides a general background on cytochrome P450 (CYP) enzymes followed by wild-type CYP enzymes in the synthesis of novel drugs and drug metabolites, limitations, CYP engineering for enhanced activity, stability, and specificity to overcome the limitations, advantages of using CYP enzymes for drugs and drug metabolites synthesis, and conclusion and future prospects. As a large group of biocatalysts, CYP family of enzymes play an indispensable role in the metabolism of both endogenous and exogenous compounds. CYP enzymes are a membrane-bound, superfamily of heme containing enzymes with more than 21,000 members throughout nature. Utilization of bacterial CYP enzymes in drug synthesis dates back to early 1950s when cortisone was converted from progesterone by introducing hydroxyls into sterols, in Rhizopus culture. Plant specific metabolites, such as terpenoids, phenylpropanoids, and nitrogen-containing compounds are the major source of new drugs and bioactive compounds. Plant CYP enzymes have the potential to be used for industrial hydroxylation reactions.