Leveraging ecological theory to guide natural product discovery

Technological improvements have accelerated natural product (NP) discovery and engineering to the point that systematic genome mining for new molecules is on the horizon. NP biosynthetic potential is not equally distributed across organisms, environments, or microbial life histories, but instead is enriched in a number of prolific clades. Also, NPs are not equally abundant in nature; some are quite common and others markedly rare. Armed with this knowledge, random ‘fishing expeditions’ for new NPs are increasingly harder to justify. Understanding the ecological and evolutionary pressures that drive the non-uniform distribution of NP biosynthesis provides a rational framework for the targeted isolation of strains enriched in new NP potential. Additionally, ecological theory leads to testable hypotheses regarding the roles of NPs in shaping ecosystems. Here we review several recent strain prioritization practices and discuss the ecological and evolutionary underpinnings for each. Finally, we offer perspectives on leveraging microbial ecology and evolutionary biology for future NP discovery.