Acyl-phosphates initiate membrane phospholipid synthesis in Gram-positive pathogens.
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.
Lu
Ying-Jie
YJ
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Zhang
Yong-Mei
YM
Grimes
Kimberly D
KD
Qi
Jianjun
J
Lee
Richard E
RE
Rock
Charles O
CO
D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis*; D013296:Streptococcus pneumoniae / Q000378:metabolism*
D001426:Bacterial Proteins; D010710:Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; C088150:plsX protein, bacteria; D005992:Glycerol-3-Phosphate O-Acyltransferase