Acyl homoserine-lactone quorum-sensing signal generation
Acyl homoserine-lactone quorum-sensing signal generation
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DOI：
10.1073/pnas.96.8.4360
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发表时间：
1999-04-13
影响因子：
11.1
通讯作者：
Greenberg, EP
中科院分区：
文献类型：
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作者：
Parsek, MR;Val, DL;Greenberg, EP
酰基高丝氨酸内酯（acylhomoserine lactones，acL-HSL）是一类重要的细胞间信号分子，在细菌群体感应调控基因表达中起着重要的调控作用。这些信号是由LuxI家族蛋白合成的。为了了解酰基-HSL合成的机制，我们纯化了铜绿假单胞菌RhlI蛋白，并分析了该酶合成酰基-HSL的动力学。产物抑制模式的分析表明，RhlI催化信号合成的顺序，有序的反应机制，其中S-腺苷甲硫氨酸结合RhlI作为酶机制的初始步骤。由于病原菌如铜绿假单胞菌使用酰基-HSL信号来调节毒力基因，因此理解信号合成的机制和鉴定信号合成的抑制剂对于群体感应靶向的抗毒力分子的开发具有意义。
Acyl homoserine lactones (acyl-HSLs) are important intercellular signaling molecules used by many bacteria to monitor their population density in quorum-sensing control of gene expression. These signals are synthesized by members of the LuxI family of proteins, To understand the mechanism of acyl-HSL synthesis we have purified the Pseudomonas aeruginosa RhlI protein and analyzed the kinetics of acyl-HSL synthesis by this enzyme, Purified RhlI catalyzes the synthesis of acyl-HSLs from acyl-acyl carrier proteins and S-adenosylmethionine. An analysis of the patterns of product inhibition indicated that RhlI catalyzes signal synthesis by a sequential, ordered reaction mechanism in which S-adenosylmethionine binds to RhlI as the initial step in the enzymatic mechanism. Because pathogenic bacteria such as P. aeruginosa use acyl-HSL signals to regulate virulence genes, an understanding of the mechanism of signal synthesis and identification of inhibitors of signal synthesis has implications for development of quorum sensing-targeted antivirulence molecules.