First functional expression of cytochrome P450 3A4 in Pichia pastoris

Getting access to drug metabolites has become an important issue within the drug discovery and development process. Besides chemical synthesis and chromatographic separation, the selective production of these metabolites employing whole-cell biotransformations with recombinant microbes has become an emerging strategy.
Here, we report for the first time the functional expression of the human cytochrome P450 3A4 (CYP3A4), a key enzyme in drug metabolism, in the methylotrophic yeast Pichia pastoris. Co-expression of the human cytochrome b5 and/or the cytochrome P450 reductase (CPR) yielded in a functional whole-cell monooxygenase catalyst