Synthetic Simplification of Carolacton Enables Chemical Genetic Studies in .

Understanding the broader biological impact of carolacton, a macrolactone natural product, has been ongoing for the past decade. Multiple studies have shown connections to regulatory systems, acid tolerance mechanisms, biofilm formation, and recently folate dehydrogenase (FolD). Progress elucidating the cause of biofilm-specific activity in has been limited due to low-throughput analyses of carolacton-treated cells. We disclose the discovery of a simplified carolacton-inspired analog that demonstrates inhibitory activity against biofilm cells. This discovery permitted a proof of concept chemical genetic screen of mutants identifying the carbon catabolite protein A signaling pathway as a putative target.