The industrial anaerobe Clostridium acetobutylicum uses polyketides to regulate butanol production and differentiation

Polyketides are an important class of bioactive small molecules valued not only for their diverse therapeutic applications, but also for their role in controlling interesting biological phenotypes in their producing organisms. While numerous examples of polyketides derived from aerobic organisms exist, only a single family of polyketides has been identified from anaerobic organisms. Here we uncover a novel family of polyketides native to the anaerobic bacterium Clostridium acetobutylicum, an organism well-known for its historical use as an industrial producer of the organic solvents acetone, butanol, and ethanol. Through mutational analysis and chemical complementation assays, we demonstrate that these polyketides influence butanol production and act as chemical triggers of sporulation and granulose accumulation in this strain. This study represents a significant addition to the body of work demonstrating the existence and importance of polyketides in anaerobes, and showcases a novel strategy of manipulating the secondary metabolism of an organism to improve traits significant for industrial applications.