(342c) Engineering Natural Product Biosynthesis and Biocatalysis

Microbial natural products that have potent biological activities are important sources of pharmaceuticals.  In nature, these complex small molecules are assembled from simple primary metabolites using elaborate biosynthetic pathways and enzymes.  Understanding the biosynthesis of these compounds is therefore an important goal towards rationally engineering new drug candidates.  Our lab is interested in the biosynthesis of compounds that have antibiotic, anticancer and cholesterol lowering activities.  In this presentation, I will discuss the strategies towards manipulating natural product pathways in microorganisms, especially towards the mining of new compounds with novel activities.   Recent sequencing efforts have revealed that an overwhelming number of natural products gene clusters are silent under normal laboratory culturing conditions.  Hence activation of these pathways is potentially a new source for drug discovery.  Several examples in both soil-borne actinomycetes and filamentous fungi will be presented.