The convergence of bacterial natural products from evolutionarily distinct pathways

As bacteria readily convert simple starting materials into a diverse array of complex molecules with useful bioactivities, these microorganisms and their biosynthetic machinery represent attractive alternatives to traditional chemical syntheses. While the well-documented divergent evolution of biosynthesis has allowed bacteria to explore wide swaths of natural product chemical space, the convergent evolution of these pathways remains a comparably rare phenomenon. The emergence of similar phenotypes within disparate genetic contexts provides a unique opportunity to probe the limitations of natural selection and the predictability and reproducibility of evolution under different constraints. Here, we report several recent examples of functional and structural convergence of bacterial natural products, as well as intra- and inter-domain convergence of bacterial biosynthetic machinery. While the genetic underpinnings of biosynthetic pathway evolution are of fundamental interest, the evolutionary constraints exemplified by phenotypic convergence also have immediate implications for efforts to engineer microorganisms for therapeutic small molecule production.