Joris Beld, Ph. D.
Department of Microbiology and Immunology
Center for Advanced Microbial Processing
Institute for Molecular Medicine & Infectious Disease
Drexel University College of Medicine
“Utilization of environmental fatty acids by bacteria”
Fatty acids are essential to most living organisms since they are the building blocks of lipids. Consisting of a carboxylic acid headgroup and a hydrophobic tail of 14-22 carbons long, they have unique properties required for membrane fluidity. Bacteria endogenously produce fatty acids by the fatty acid synthase (FAS), a complex molecular machine that uses ATP and acetyl-CoA to make fatty acids in an iterative way starting from 2 carbon units. Fatty acid biosynthesis is energy intensive, and fatty acids are used as energy storage by eukaryotes and some prokaryotes. The break-down of fatty acids through the process of beta-oxidation liberates this energy. Bacteria not only biosynthesize and break-down their own fatty acids, but also take-up and utilize environmental fatty acids. Many can use fatty acids as nutrient source, catabolize fatty acids into ATP and acetyl-CoA units, which then can be used for anabolism. However, some bacteria can utilize environmental fatty acids directly for incorporation into lipids, without the need for catabolism. This process is facilitated through the activity of an acyl-acyl carrier protein synthetase (AasS) which loads fatty acids onto the acyl carrier protein (ACP) of the FAS. By sequence, AasS resembles acyl-coenzyme A synthetases but instead of loading the small molecule CoA, it loads fatty acids onto a protein. Using a combination of unnatural fatty acid supplementation and mass spectrometry we identified an AasS in Vibrio cholerae. In vitro characterization showed that the enzyme can load diverse fatty acids on the FAS acyl carrier protein. The activity of AasS allows V. cholerae to circumvent FAS inhibition by taking up fatty acids from its environment and utilizing them directly. Synthesis of an AasS inhibitor allowed us to show this in living bacteria. Understanding how bacteria utilize environmental fatty acids is crucial, especially with several FAS-targeted antibiotics in the pipeline.
Lecture 5 to 6pm