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...

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Veröffentlicht in:Molecular cell 2006-09, Vol.23 (5), p.765-772
Hauptverfasser: Lu, Ying-Jie, Zhang, Yong-Mei, Grimes, Kimberly D., Qi, Jianjun, Lee, Richard E., Rock, Charles O.
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Sprache:eng
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Zusammenfassung: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2006.06.030