Drees Steffen Lorenz, Fetzner Susanne
Institute of Molecular Microbiology and Biotechnology, University of Münster, Corrensstrasse 3, 48149 Münster, Germany.
Institute of Molecular Microbiology and Biotechnology, University of Münster, Corrensstrasse 3, 48149 Münster, Germany.
Chem Biol. 2015 May 21;22(5):611-8. doi: 10.1016/j.chembiol.2015.04.012. Epub 2015 May 7.
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.
铜绿假单胞菌利用烷基喹诺酮类物质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，根据细胞群体密度控制许多毒力基因的表达。普遍认为HHQ的生物合成需要pqsABCD基因产物。我们现在在体外重建了生物合成途径，并证明除了PqsABCD外，PqsE在HHQ合成中也发挥作用。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以形成2-氨基苯甲酰乙酸，这是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缺失突变体仍然能合成HHQ。有趣的是，pqsE突变体产生的2,4-二羟基喹啉水平增加，这是由2-氨基苯甲酰乙酰辅酶A的分子内环化产生的。总体而言，我们的数据表明PqsE促进了铜绿假单胞菌中烷基喹诺酮信号分子生物合成的效率，并平衡了源自烷基喹诺酮生物合成途径的次生代谢产物的水平。
