Acyl-phosphates initiate membrane phospholipid synthesis in Gram-positive pathogens |
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Authors: | Lu Ying-Jie Zhang Yong-Mei Grimes Kimberly D Qi Jianjun Lee Richard E Rock Charles O |
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Institution: | Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. |
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Abstract: | 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. |
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