Abstract
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 .