Sunday, August 1, 2010
Pacific Concourse (Hyatt Regency San Francisco)
Drug metabolism is an important aspect of the testing required to evaluate the safety and efficacy of a new pharmaceutical compound. Human cytochrome P450 monooxygenases (CYPs) are primarily expressed in the liver and are predominantly responsible for Phase 1 metabolism of pharmaceutical compounds. AMRI scientists have developed technology for the production and use of several of the most important cytochrome P450 isoforms using recombinant E. coli. Seven cytochrome P450 isoforms are available: 1A1, 1A2, 2C10, 2C19, 2D6, 2E1, and 3A4. Fermentation parameters have been evaluated for the efficient production of these recombinant enzymes up to a 14-L scale. The active enzymes from the recombinant E. coli can be used as whole cell suspensions or microsomal preparations. This technology has been successfully used to prepare metabolites of a wide variety of compounds, and reaction scale-up has been demonstrated up to 1.0 L for the production of larger quantities of metabolites.