Biosynthesis and Evaluation of Benzoisochromanequinones

Stanford University, Stanford CA

Investigators

Abstract

DESCRIPTION (provided by applicant): The benzoisochromanequinones (BIQs) are a family of aromatic polyketides of which members have been found to possess significant biological activities including selective inhibition of the anti-cancer target farnesyltransferase (FTase), toxicity to tumor cells in both in vitro and in vivo assays, and inhibition of multi-drug resistant and susceptible strains of bacteria. Much is now known about the polyketide genes and proteins responsible for the biosynthesis of these compounds, and we propose to construct a library of novel BIQ analogs through metabolic engineering and combinatorial biosynthesis. We intend to evaluate these analogs for activity against multi-drug and susceptible strains of Staphylococcus aureus, a fibroblast and K- 562 leukemia cell line, and FTase and geranylgeranyltransferase I enzymes. The results from screening the BIQ library in this panel would allow evaluation of the selectivity of the various compounds and the identification of any BIQ analogs with superior bioactivity.