Abstract 2470 A copper-containing antibiotic produced by Pseudomonas

Pseudomonas species colonize and infect a broad range of eukaryotic hosts. Infection by these bacteria can significantly impact the diversity and composition of the microbiota of the hosts. Pseudomonas produce many natural products, including antibiotics, toxins, and signaling molecules. These molecules play essential roles in microbe-microbe and microbe-host interactions. This talk describes the identification, biosynthesis, and activity of an unusual copper-containing antibiotic, fluopsin C, produced by the opportunistic human pathogen Pseudomonas aeruginosa. The biosynthesis of fluopsin C requires five enzyme-catalyzed reactions, including a unique methine excision reaction. The biosynthetic gene cluster of fluopsin C is conserved in nearly 5,000 P. aeruginosa genomes and distributed in many other human pathogens and plant colonizers. Thus, fluopsin C likely plays a conserved physiological role in these bacteria. This work uncovers new enzyme-catalyzed chemistry and chemical interactions between P. aeruginosa and commensal microbes. This work is supported by the National Institutes of Health (DP2HD094657 and R01GM148685 to B.L.; GM137286 to M.R.R., GM111978 and GM126303 to M.-E.P.) and Packard Fellowship of Science and Engineering (B.L.). T.L.G. acknowledges funding from the Searle Scholars Program.