Microbial biotransformation – an important tool for the study of drug metabolism

Abstract

1. Metabolite identification is an integral part of both preclinical and clinical drug discovery and development. Synthesis of drug metabolites is often required to support definitive identification, preclinical safety studies and clinical trials.

2. Here we describe the use of microbial biotransformation as a tool to produce drug metabolites, complementing traditional chemical synthesis and other biosynthetic methods such as hepatocytes, liver microsomes and recombinant human drug metabolizing enzymes.

3. A workflow is discussed whereby microbial strains are initially screened for their ability to form the putative metabolites of interest, followed by a scale-up to afford quantities sufficient to perform definitive identification and further studies.

4. Examples of the microbial synthesis of several difficult-to-synthesize hydroxylated metabolites and three difficult-to-synthesize glucuronidated metabolites are described, and the use of microbial biotransformation in drug discovery and development is discussed.

Keywords:

• Bacteria
• fungi
• metabolite synthesis
• hydroxylation
• glucuronidation

Acknowledgments

The authors would like to thank the many members of Janssen Research and Development LLC, Merck & Co., Inc., Kenilworth, NJ, USA, and Hypha Discovery Ltd. Who made contributions to this work.

Disclosure statement

No potential conflict of interest was reported by the authors.