PqsE of Pseudomonas aeruginosa Acts as Pathway-Specific Thioesterase in the Biosynthesis of Alkylquinolone Signaling Molecules
PqsE of Pseudomonas aeruginosa Acts as Pathway-Specific Thioesterase in the Biosynthesis of Alkylquinolone Signaling Molecules
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DOI：
10.1016/j.chembiol.2015.04.012
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发表时间：
2015-05-21
影响因子：
--
通讯作者：
Fetzner, Susanne
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文献类型：
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作者：
Drees, Steffen Lorenz;Fetzner, Susanne
铜绿假单胞菌使用烷基喹诺酮类PQS（2-庚基-3-羟基-4（1H）-喹诺酮）和HHQ（2-庚基-4（1H）-喹诺酮）作为群体感应信号分子，控制许多毒力基因的表达作为细胞群体密度的函数。一般认为HHQ的生物合成需要pqsABCD基因产物。我们现在重建的生物合成途径在体外，并证明，除了PqsABCD，PqsE有一个作用，在HHQ的合成。PqsE作为硫酯酶，水解生物合成中间体2-氨基苯甲酰乙酰辅酶A，形成2-氨基苯甲酰乙酸，HHQ和2-氨基苯乙酮的前体。PqsE的作用可以在一定程度上被广泛特异性硫酯酶TesB取代，这解释了为什么铜绿假单胞菌的pqsE缺失突变体仍然合成HHQ。有趣的是，pqsE突变体产生增加水平的2，4-二羟基喹啉，这是由2-氨基苯甲酰乙酰辅酶A的分子内环化引起的。总体而言，我们的数据表明，PqsE促进铜绿假单胞菌中烷基喹诺酮信号分子生物合成的效率，并平衡源自烷基喹诺酮生物合成途径的次级代谢产物的水平。
Pseudomonas aeruginosa uses the alkylquinolones PQS (2-heptyl-3-hydroxy-4(1H)-quinolone) and HHQ (2-heptyl-4(1H)-quinolone) as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. The biosynthesis of HHQ is generally accepted to require the pqsABCD gene products. We now reconstitute the biosynthetic pathway in vitro, and demonstrate that in addition to PqsABCD, PqsE has a role in HHQ synthesis. PqsE acts as thioesterase, hydrolyzing the biosynthetic intermediate 2-aminobenzoylacetyl- coenzyme A to form 2-aminobenzoylacetate, the precursor of HHQ and 2-aminoacetophenone. The role of PqsE can be taken over to some extent by the broad-specificity thioesterase TesB, explaining why the pqsE deletion mutant of P. aeruginosa still synthesizes HHQ. Interestingly, the pqsE mutant produces increased levels of 2,4-dihydroxyquinoline, resulting from intramolecular cyclization of 2-aminobenzoylacetyl-coenzyme A. Overall, our data suggest that PqsE promotes the efficiency of alkylquinolone signal molecule biosynthesis in P. aeruginosa and balances the levels of secondary metabolites deriving from the alkylquinolone biosynthetic pathway.