biostudies-literaturePatteson JBNICHD NIH HHSNIGMS NIH HHS1005-1009https://www.ebi.ac.uk/biostudies/studies/S-EPMC8939262biostudies-literatureUnknown374(6570)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 <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> 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.Science (New York, N.Y.)Biosynthesis of fluopsin C, a copper-containing antibiotic from <i>Pseudomonas aeruginosa</i>.PMC8939262R35 GM126961T32 GM008570DP2 HD094657Britt RDTao LBryant LHSimke WCLi BPutz ATPatteson JBfalseBiosynthesis of fluopsin C, a copper-containing antibiotic from <i>Pseudomonas aeruginosa</i>.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 <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> 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.2021-01-01T00:00:00Z2021 Nov2024-11-09T22:27:45.109Z2024-11-09T22:27:45.109ZS-EPMC89392623479321310.1126/science.abj6749