Pseudomonas aeruginosa is a bacterial pathogen that causes life-threatening infections in immunocompromised patients. It produces a large armory of saturated and mono-unsaturated 2-alkyl-4(1H)-quinolones (AQs) and AQ N-oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β-ketoacyl-acyl-carrier protein synthase III (FabH)-like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2-heptyl-4(1H)-quinolone (HHQ), by condensing octanoyl-coenzyme A (CoA) with 2-aminobenzoylacetate (2-ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium-chain acyl-CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono-unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl-binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH-enzymes, for which such structural transitions have been postulated but have never been observed.

中文翻译：

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铜绿假单胞菌的烷基喹诺酮库与FabH样2-庚基-3-羟基-4（1H）-喹诺酮（PQS）生物合成酶PqsBC的结构柔性有关。

铜绿假单胞菌是一种细菌病原体，可在免疫功能低下的患者中造成威胁生命的感染。它产生大量的饱和和单不饱和2-烷基-4（1H）-喹诺酮（AQs）和AQ N-氧化物（AQNOs）军械库，它们充当信号分子来控制毒力因子的产生，并参与膜囊泡形成和铁螯合；此外，它们还具有例如抗生素特性。已经显示，β-酮酰基-酰基-载体蛋白合酶III（FabH）样异二聚酶PqsBC催化了最丰富的AQ同源物2-庚基-4（1H）-喹诺酮（HHQ）的生物合成的最后一步。 ），通过将辛酰基辅酶A（CoA）与2-氨基苯甲酰乙酸酯（2-ABA）进行缩合，但是由铜绿假单胞菌产生的大量其他AQ / AQNO的基础尚不清楚。这里，我们证明PqsBC使用不同的中链酰基CoA来产生各种饱和AQ / AQNO，并且它还可以生物合成单不饱和同类物。此外，我们以1.5到2.7Å的分辨率确定了四种不同晶体形式的PqsBC的结构。连同先前的报告，数据显示PqsBC采用开放，中间和封闭的构象，这些构象改变了酰基结合腔的形状并解释了PqsBC的滥交情况。不同的构象也使我们能够为PqsBC催化循环所伴随的结构转变提出一个模型，该模型可能对其他FabH酶具有更广泛的意义，但对于这种结构转变，我们已经假定但从未观察到。