Acyl-phosphates initiate membrane phospholipid synthesis in Gram-positive pathogens

Mol Cell. 2006 Sep 1;23(5):765-72. doi: 10.1016/j.molcel.2006.06.030.


It is not known how Gram-positive bacterial pathogens carry out glycerol-3-phosphate (G3P) acylation, which is the first step in the formation of phosphatidic acid, the key intermediate in membrane phospholipid synthesis. In Escherichia coli, acylation of the 1-position of G3P is carried out by PlsB; however, the majority of bacteria lack a plsB gene and in others it is not essential. We describe a two-step pathway that utilizes a new fatty acid intermediate for the initiation of phospholipid formation. First, PlsX produces a unique activated fatty acid by catalyzing the synthesis of fatty acyl-phosphate from acyl-acyl carrier protein, and then PlsY transfers the fatty acid from acyl-phosphate to the 1-position of G3P. The PlsX/Y pathway defines the most widely distributed pathway for the initiation of phospholipid formation in bacteria and represents a new target for the development of antibacterial therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • Cell Membrane / chemistry*
  • Escherichia coli / metabolism
  • Glycerol-3-Phosphate O-Acyltransferase / metabolism
  • Phosphates / metabolism*
  • Phosphatidylinositols / biosynthesis
  • Phospholipids / biosynthesis*
  • Streptococcus pneumoniae / metabolism*


  • Bacterial Proteins
  • Phosphates
  • Phosphatidylinositols
  • Phospholipids
  • plsX protein, bacteria
  • Glycerol-3-Phosphate O-Acyltransferase