A new pathway of exogenous fatty acid incorporation proceeds by a classical phosphoryl transfer reaction

The Firmicute bacteria readily incorporate exogenous fatty acids into their phospholipids. In some (but not all) family members incorporation of the fatty acids present in human serum precludes the use of fatty acid synthesis inhibitors to treat infections. However, the pathway(s) of exogenous fatty acid incorporation in these bacteria remained unknown, although it was thought to differ from known pathways. Parsons and co-workers show that in Staphylococcus aureus exogenous fatty acids are activated by phosphoryl transfer from ATP to form acyl-phosphates, a mixed anhydride suggested as a potential intermediate 70 years ago. This finding has important ramifications for the efficacy of treatment of S. aureus infections using inhibitors of fatty acid synthesis.