Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis

摘要: The recent discovery of fatty acyl-AMP ligases (FAALs) in Mycobacterium tuberculosis (Mtb) provided a new perspective to acid activation dogma. These proteins convert acids corresponding adenylates, which is an intermediate acyl-CoA-synthesizing acyl-CoA (FACLs). Presently, it not evident how obligate pathogens like Mtb have evolved such themes functional versatility and whether the acyl-adenylates could indeed be general mechanism. Here, based on elucidation first structure FAAL protein by generating loss- as well gain-of-function mutants that interconvert FACL activities, we demonstrate insertion motif dictates formation acyl-adenylate. Since FAALs are crucial nodes biosynthetic network virulent lipids, inhibitors directed against these provide unique multi-pronged approach simultaneously disrupting several pathways.