美国北卡罗来纳大学教堂山分校Bo Li研究组揭示了铜绿假单胞菌含铜抗生素氟蛋白C的生物合成途径。该研究于2021年11月19日发表于国际学术期刊《科学》杂志。

研究人员发现铜绿假单胞菌利用五酶途径合成小分子铜复合物-氟蛋白C，以响应铜浓度升高。氟蛋白C是一种广谱抗生素，其含有一个铜离子，由两种最小的硫代异羟肟酸盐螯合。硫代异羟肟酸的生物合成起始于半胱氨酸，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。

该通路在铜绿假单胞菌和其他细菌中的保守表明氟蛋白C在铜应激反应中的共同作用，这有助于将铜融合到一种抗生素中以对抗其他微生物。

据悉，具有金属结合能力的天然产物对于细菌金属获取和毒力至关重要，但尚不清楚它们在金属应激反应中的作用。

附：英文原文

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

Author: Jon B. Patteson, Andrew T. Putz, Lizhi Tao, William C. Simke, L. Henry BryantIII, R. David Britt, Bo Li

Issue&Volume: 2021-11-19

Abstract: 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.

DOI: abj6749

Source: https://www.science.org/doi/10.1126/science.abj6749