Monday, August 2, 2010
Pacific Concourse (Hyatt Regency San Francisco)
Efficient fermentation process development and scale-up is critical for any natural product based drug discovery program in order to provide starting material in sufficient quantities to support a robust semi-synthesis - SAR campaign. Here we describe the successful scale-up of a streptomyces fermentation for the production of the ansamycin polyketide, Geldanamycin. During the course of this campaign the Metabolism and Biotransformations group developed a small scale (13L) fermentation process with titers that were 130-fold greater than starting titers and six folded greater than the maximum titers reported in the literature. This process was then successfully scaled-up to a 500L fermentation. Over the course of the scale-up effort, 4 kilograms of Geldanamycin was delivered to AMRI’s GMP and Chemical Development groups as a starting material for the GMP production of the hsp90 inhibitor, 17-AAG.