Enzymatic synthesis of pharmaceutical intermediates

MEDI 575

Brian Morgan, bmorgan@diversa.com1, Grace DeSantis, gdesantis@diversa.com1, Nelson Barton1, David P. Weiner1, William A. Greenberg, wgreenb@scripps.edu2, and Mark J. Burk, mburk@diversa.com1. (1) Diversa Corporation, 4955 Directors Place, San Diego, CA 92121, (2) Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037
Biocatalysis has become increasingly important for the preparation of chiral fine chemical and pharmaceutical intermediates. However, to fully exploit the potential of biocatalysis, access to novel enzymes with high activity, enhanced thermal and pH stability, and high chemo- regio- and enantioselectivity is necessary. Using high-throughput screening of genomic DNA libraries prepared from samples from diverse environments, we have assembled a collection of enzymes that catalyze a range of useful transformations. The challenges involved in progressing these enzymes from the initial discovery phase to the final process conditions will be discussed using aldolases, amidases, esterases and nitrilases as examples.