Lu Ying-Jie, Zhang Yong-Mei, Grimes Kimberly D, Qi Jianjun, Lee Richard E, Rock Charles O
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
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.
目前尚不清楚革兰氏阳性细菌病原体是如何进行3-磷酸甘油（G3P）酰化的，这是磷脂酸形成的第一步，而磷脂酸是膜磷脂合成的关键中间体。在大肠杆菌中，G3P 1位的酰化由PlsB进行；然而，大多数细菌缺乏plsB基因，在其他细菌中它也不是必需的。我们描述了一种利用新的脂肪酸中间体启动磷脂形成的两步途径。首先，PlsX通过催化从酰基-酰基载体蛋白合成脂肪酰磷酸来产生一种独特的活化脂肪酸，然后PlsY将脂肪酸从酰基磷酸转移到G3P的1位。PlsX/Y途径定义了细菌中最广泛分布的磷脂形成起始途径，并且代表了抗菌治疗药物开发的新靶点。
