Production of human phase 1 and 2 metabolites by whole-cell biotransformation with recombinant microbes

Abstract

Cytochrome P450 enzymes (CYPs or P450s) are the most important enzymes involved in the phase I metabolism of drugs and poisons in humans, while UDP glycosyltransferases catalyze the majority of phase II reactions. In addition, a number of other enzymes or enzyme families contribute to the metabolism of xenobiotica, including alcohol dehydrogenase, aldehyde dehydrogenase, ester and amide hydrolases, epoxide hydrolase and flavine monooxygenases, as well as sulfotransferases, catechol-O-methyltransferase and N-acetyltransferase. A thorough understanding of their activity and of the properties of the metabolites they form is an essential prerequisite for the assessment of drug-caused side effects or toxicity. In this context of MIST, efficient production systems are needed to permit the large-scale production of human drug metabolites. As classical chemical synthesis cannot always provide these metabolites, biotechnological approaches have been developed that typically employ the recombinant expression of human drug-metabolizing enzymes. This review summarizes the current knowledge regarding whole-cell biotransformation processes that make use of such an approach.