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.

中文翻译：

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铜绿假单胞菌中的含铜抗生素氟视素 C 的生物合成

金属结合天然产物有助于金属获取和细菌毒力，但它们在金属应激反应中的作用尚未得到充分研究。我们发现，铜绿假单胞菌中的五酶途径会响应铜浓度升高而合成小分子铜复合物氟视蛋白 C。Fluopsin C 是一种广谱抗生素，含有由两个最小的硫代羟肟酸盐螯合的铜离子。硫代羟肟酸的生物合成从半胱氨酸开始，需要两种裂解酶、两种铁依赖性酶和一种甲基转移酶。铁依赖性酶通过脱羧、N-羟基化和亚甲基切除从半胱氨酸中去除羧基和 α 碳。铜绿假单胞菌和其他细菌中该途径的保守性表明氟视蛋白 C 在铜应激反应中发挥着共同作用，其中涉及将铜融合到对抗其他微生物的抗生素中。