Chemical Perturbation of Secondary Metabolism Demonstrates Important Links to Primary Metabolism

SummaryBacterially produced secondary metabolites are used as antibiotics, anticancer drugs, and for many other medicinal applications. The mechanisms that limit the production of these molecules in the laboratory are not well understood, and this has impeded the discovery of many important compounds. We have identified small molecules that remodel the yields of secondary metabolites in many actinomycetes and show that one set of these molecules does so by inhibiting fatty acid biosynthesis. This demonstrates a particularly intimate relationship between this primary metabolic pathway and secondary metabolism and suggests an approach to enhance the yields of metabolites for discovery and biochemical characterization.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (261 K)Download as PowerPoint slideHighlights► A chemical screen recapitulates all genetic phenotypes in S. coelicolor ► 19 compounds remodel secondary metabolism in Streptomyces coelicolor ► Partial inhibition of fatty acid synthesis remodels secondary metabolite production