Using mass spectrometry to assign the function of orphan genes involved in the biosynthesis of secondary metabolites

BIOL 109

Pieter C. Dorrestein, pdorrestein@ucsd.edu, Skaggs School of Pharmacy and Departments of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92121
This lecture is to honor Neil L. Kelleher for his receipt of the Pfizer award for his contributions to enzymology. One of the challenges in the post-genomic era is to assign functional roles to orphan genes. Here we describe mass spectrometry based approaches to assign the functional roles of proteins involved in the production of secondary metabolites that have therapeutic value. We demonstrate the use of these tools in the characterization of the genes found on orphan biosynthetic pathways responsible for the biogenesis of the hemolytic factors in streptococci. Although these hemolytic activities have been known for a century, their structures of the secondary metabolites are an unsolved mystery but we are beginning to understand some of the functional roles of the genes involved in their biogenesis and will be presented in this lecture.