S108: Structural characterization of enzymes involved in the biosynthesis of phosphonate natural products

Tuesday, August 3, 2010: 3:00 PM
Seacliff CD (Hyatt Regency San Francisco)
Satish K. Nair, Brian Bae, Houjin Zhang, Rob Cicchillo, Jin Hee Lee, John Whitteck, Matt DeSieno, Ryan Cobb, Huimin Zhao, William Metcalf and Wilfred van der Donk, Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL
Research interest in natural products containing phosphonate or phosphinate groups has continued to increase as genome-mining studies have yielded many bioactive molecules with antibiotic, antimalarial and herbicidal properties.  The activities of these compounds are predicated on their structural similarity to phosphate esters and carboxylic acids, combined with the hydrolytically stability of the P-C bond.  Here, we present the results of our recent biochemical, and microbiological studies on enzymes that are involved in the biosynthesis of the anatimalarial FR900098, the antibiotic dehydrophos, and the herbicide phosphinothricin tripeptide.  Crystallographic studies of several such enzymes present avenues for the reprogramming of substrate specificities, towards the production of derivative compounds that may display enhanced bioactivity and bioavailability.