Research in our laboratory is focused upon the biosynthesis of secondary metabolites, otherwise known as natural products. Many of these compounds exhibit a high degree of chemical complexity as well as important biological activity. Examples of such compounds include the important antibiotics erythromycin, penicillin, and vancomycin. The goals of our research are to discover novel biochemical reactions associated with specific biosynthetic pathways and to engineer biosynthetic gene clusters to produce new compounds with desirable biological activity.Â Several natural products are currently under intensive study in our laboratories.
One of these compounds is the antitumor antibiotic valanimycin, an azoxy compound produced by Streptomyces viridifaciens. Valanimycin is a member of a growing class of natural products that contain N-N bonds. Although compounds with N-N bonds are widespread, little is known at present about the biochemistry involved in N-N bond formation. A major goal of this project is to discover the nature of the N-N bond forming chemistry. The entire cluster of genes required for valanimycin biosynthesis has now been cloned and sequenced, but the genes encoding the proteins responsible for N-N bond formation have not yet been identified. Two other ongoing projects are concerned with the biosynthesis of the phytotoxin coronatine and the biosynthesis of the antibiotics of the pyrrolomycin complex. Coronatine and the pyrrolomycins possess unusual structural features indicating that novel biochemistry is involved in their biosynthesis.