Fig. 5. Phosphatidic acid synthesis and exogenous fatty acid incorporation in Gram-positive bacteria.

Gram-positive bacteria utilize the PlsX/PlsY pathway for the synthesis of phosphatidic acid. PlsX converts acyl-ACP into acyl-phosphate, which is used as the acyl donor by the acyltransferase PlsY in the synthesis of lysophosphatidic acid. PlsC utilizes acyl-ACP as the acyl donor to generate phosphatidic acid. Exogenous fatty acids are converted into acyl-phosphates by the fatty acid kinase system FakA/B. The resulting acyl-phosphate can be converted into acyl-ACP by the acyl-ACP:phosphate transacylase PlsX. The resulting acyl-ACP can be elongated by the FASII, used by PlsC, or converted back into acyl-phosphate. Exogenous fatty acids can bypass the inhibition of FASII in Lactobacillales but not Bacillales. This difference is due to how exogenous fatty acids regulate endogenous fatty acid synthesis in these two bacterial orders. In Lactobacillales, exogenous fatty acids cause a dose dependent and complete inhibition of the endogenous synthesis of fatty acids, effectively rendering FASII inactive and bypassed. In Bacillales, exogenous fatty acids cause a dose dependent, but only partial inhibition of the endogenous synthesis of fatty acids. Inhibition of FASII in Bacillales causes depletion of the free ACP pool by tying them up as short chain acyl-ACP. Exogenous fatty acids cannot be converted into acyl-ACP, and phospholipid synthesis is halted.