The first domain of modular polyketide synthases (PKSs) is most commonly a ketosynthase (KS)-like enzyme, KS^Q, that primes polyketide synthesis. Unlike downstream KSs that fuse α-carboxyacyl groups to growing polyketide chains, it performs an extension-decoupled decarboxylation of these groups to generate primer units. When Pik127, a model triketide synthase constructed from modules of the pikromycin synthase, was studied by cryoelectron microscopy (cryo-EM), the dimeric didomain comprised of KS^Q and the neighboring methylmalonyl-selective acyltransferase (AT) dominated the class averages and yielded structures at 2.5- and 2.8-Å resolution, respectively. Comparisons with ketosynthases complexed with their substrates revealed the conformation of the (2S)-methylmalonyl-S-phosphopantetheinyl portion of KS^Q and KS substrates prior to decarboxylation. Point mutants of Pik127 probed the roles of residues in the KS^Q active site, while an AT-swapped version of Pik127 demonstrated that KS^Q can also decarboxylate malonyl groups. Mechanisms for how KS^Q and KS domains catalyze carbon-carbon chemistry are proposed.

模块化聚酮合酶 (PKS) 的第一个结构域最常见的是类酮合酶 (KS) KS ^Q，它启动聚酮合酶的合成。与将 α-羧酰基融合到不断增长的聚酮化合物链的下游 KS 不同，它对这些基团进行延伸解耦脱羧以生成引物单元。当通过冷冻电子显微镜 (cryo-EM) 研究 Pik127（一种由匹克霉素合酶模块构建的模型三酮化合物合酶）时，由 KS Q 和邻近的甲基丙二酰选择性酰基转移酶 (AT) 组成的二聚体双结构域在类别平均值中占主导地位并产生^了结构分辨率分别为 2.5 和 2.8 Å。与与其底物复合的酮合酶的比较揭示了脱羧之前KS ^{Q和KS底物的(} 2S )-甲基丙二酰基-S-磷酸泛酰胆碱部分的构象。^{Pik127 的点突变体探测了 KS Q}活性位点中残基的作用，而 Pik127 的 AT 交换版本则证明 KS ^Q还可以使丙二酰基脱羧。提出了KS ^Q和 KS 结构域催化碳-碳化学的机制。