The Polyketide Synthase Pks13 Catalyzes a Novel Mechanism of Lipid Transfer in Mycobacteria
The Polyketide Synthase Pks13 Catalyzes a Novel Mechanism of Lipid Transfer in Mycobacteria
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DOI：
10.1016/j.chembiol.2014.10.011
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发表时间：
2014-12-18
影响因子：
--
通讯作者：
Quemard, Annaik
中科院分区：
文献类型：
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作者：
Gavalda, Sabine;Bardou, Fabienne;Quemard, Annaik
含分枝菌酸盐的化合物构成结核杆菌周围保护层的主要战略要素。我们以前已经表明，FAAL 32-Pks 13聚酮合酶催化缩合反应，产生a-烷基b-酮酸，分枝菌酸的直接前体。与目前的生物合成模型相反，我们在这里展示了Pks 13催化自身释放新合成的产物，并证明了这种功能是由其硫酯酶样结构域携带的。最重要的是，在其催化位点的海藻糖结合口袋的预测一致，该域表现出酰基转移酶活性和转移Pks 13的产品到受体分子，主要是海藻糖，导致形成的海藻糖monomycolate前体。因此，这项工作允许阐明铰链步骤的含真菌酸盐化合物的生物合成途径。最重要的是，它突出了一个独特的机制，转移聚酮合酶产品在分枝杆菌，这是不同于传统的干预离散聚酮相关蛋白（Pap）型酰基转移酶。
Mycolate-containing compounds constitute major strategic elements of the protective coat surrounding the tubercle bacillus. We have previously shown that FAAL32-Pks13 polyketide synthase catalyzes the condensation reaction, which produces a-alkyl b-ketoacids, direct precursors of mycolic acids. In contrast to the current biosynthesis model, we show here that Pks13 catalyzes itself the release of the neosynthesized products and demonstrate that this function is carried by its thioesterase-like domain. Most importantly, in agreement with the prediction of a trehalose-binding pocket in its catalytic site, this domain exhibits an acyltransferase activity and transfers Pks13's products onto an acceptor molecule, mainly trehalose, leading to the formation of the trehalose monomycolate precursor. Thus, this work allows elucidation of the hinge step of the mycolate-containing compound biosynthesis pathway. Above all, it highlights a unique mechanism of transfer of polyketide synthase products in mycobacteria, which is distinct from the conventional intervention of the discrete polyketide-associated protein (Pap)-type acyltransferases.