Biosynthesis of fluopsin C, a copper-containing antibiotic from Pseudomonas aeruginosa

Metal-binding natural products contribute to metal acquisition and Bacterial virulence, but their roles in metal stress response are underexplored. We show that a five-enzyme pathway in Pseudomonas aeruginosa synthesizes a small-molecule copper complex, fluopsin C, in response to elevated copper concentrations. Fluopsin C is a broad-spectrum Antibiotic that contains a copper ion chelated by two minimal thiohydroxamates. Biosynthesis of the thiohydroxamate begins with cysteine and requires two lyases, two iron-dependent Enzymes, and a methyltransferase. The iron-dependent Enzymes remove the carboxyl group and the α carbon from cysteine through decarboxylation, N-hydroxylation, and methylene excision. Conservation of the pathway in P. aeruginosa and Other bacteria suggests a common role for fluopsin C in the copper stress response, which involves fusing copper into an Antibiotic against Other microbes.