Natural Products and the Gene Cluster Revolution

Genome sequencing has created unprecedented opportunities for natural-product discovery and new insight into the diversity and distributions of natural-product biosynthetic gene clusters (BGCs). These gene collectives are highly evolved for horizontal exchange, thus providing immediate opportunities to test the effects of small molecules on fitness. The marine actinomycete genus Salinispora maintains extraordinary levels of BGC diversity and has become a useful model for studies of secondary metabolism. Most Salinispora BGCs are observed infrequently, resulting in high population-level diversity while conforming to constraints associated with maximum genome size. Comparative genomics is providing a mechanism to assess secondary metabolism in the context of evolution and evidence that some products represent ecotype-defining traits while others appear selectively neutral.