New approaches to microbial natural product discovery

Abstract

Microbial natural products have provided some of today's most important medicines. Despite an industrial downturn in natural product research, recent advances in the field have provided a new impetus to re-visit this resource for drug discovery. These advances have been driven in large part by ready access to genome sequence data, which has revealed that most bacteria maintain considerably more genetic potential than the compounds discovered to date, would suggest. Coupled with advanced bioinformatic tools and analytical approaches, it has become possible to mine genome sequences and link pathways to products in unprecedented ways. The results have provided unprecedented insight into the evolutionary processes that generate structural diversity and rapid methods to detect known compounds and target new molecules for characterization. Working with a model group of marine bacteria, it has been possible to apply these approaches to natural product discovery in ways that have provided insight into the relationships between secondary metabolism, biogeographic origin, and taxonomic diversity. The results are providing new opportunities to explore microbial diversity and capitalize on the wealth of biosynthetic potential that has yet to be exploited for natural product discovery.