Platt Amanda J, Ma Amy T, Beld Joris
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, 245 N 15thSt19102, USA.
Curr Microbiol. 2025 Jun 30;82(8):352. doi: 10.1007/s00284-025-04332-9.
Fatty acids are crucial building blocks for membranes, co-factors, and secondary metabolites, and they are produced by the fatty acid synthase (FAS). Several antibiotics target the bacterial FAS but some bacteria can circumvent FAS inhibition by import and utilization of exogenous fatty acids. The acyl-acyl carrier protein synthetase (AasS) facilitates the direct utilization of fatty acids without the need for breakdown through β-oxidation. Using a combination of unnatural fatty acid supplementation and mass spectrometry we identify here an AasS of Vibrio cholerae. In vitro characterization shows that the enzyme can load diverse fatty acids on the FAS acyl carrier protein as well as on coenzyme A. We show that three different FAS-targeted antibiotics can arrest growth of wild type V. cholerae and that fatty acid supplementation can rescue this inhibition. In an AasS deletion strain, supplementation with cerulenin and fatty acids allows for growth showcasing the redundancy of environmental fatty acid utilization in V. cholerae.
脂肪酸是细胞膜、辅助因子和次生代谢产物的关键组成部分，由脂肪酸合酶（FAS）产生。几种抗生素靶向细菌FAS，但一些细菌可以通过外源脂肪酸的导入和利用来规避FAS抑制。酰基-酰基载体蛋白合成酶（AasS）促进脂肪酸的直接利用，而无需通过β-氧化进行分解。通过结合非天然脂肪酸补充和质谱分析，我们在此鉴定出霍乱弧菌的一种AasS。体外表征表明，该酶可以将多种脂肪酸加载到FAS酰基载体蛋白以及辅酶A上。我们表明，三种不同的靶向FAS的抗生素可以阻止野生型霍乱弧菌的生长，而脂肪酸补充可以挽救这种抑制作用。在AasS缺失菌株中，用浅蓝菌素和脂肪酸进行补充可实现生长，这表明霍乱弧菌中环境脂肪酸利用具有冗余性。
