Key Laboratory of Chemical Biology of Natural Products, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
Key Laboratory of Chemical Biology of Natural Products, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
Plant Physiol Biochem. 2018 Apr;125:95-105. doi: 10.1016/j.plaphy.2018.01.030. Epub 2018 Jan 31.
Chalcone synthases (CHSs) of the type III polyketide synthases (PKSs), catalyze the formation of a tetraketide intermediate from a CoA-tethered starter and malonyl-CoA but use different cyclization mechanisms to produce distinct chemical scaffolds. Herein, we characterized CHS and CHS-like enzymes (designated MpCHS and MpCHSL1, 2 and 3) from Marchantia paleacea and determined the crystal structure of MpCHSL1. MpCHS catalyzed a Claisen condensation to form chalcone, while MpCHSLs catalyzed the formation of lactonized α-pyrones in vitro. Based on the structural, mutational and in vitro biochemical analyses, we established that MpCHSL1 is structurally and functionally closer to prototype CHS than stilbene synthase, and characterized the structural basis for the functional diversity of the type III PKSs. A chalcone-forming mutant of MpCHSL1 was build directed by the structural information. These findings pave the way for future studies to elucidate the functional diversity of type III PKSs in liverwort.
III 型聚酮合酶（PKSs）中的查尔酮合酶（CHSs）催化辅酶 A 连接的起始物和丙二酰辅酶 A 形成四酮中间产物，但使用不同的环化机制产生不同的化学支架。在此，我们从地钱中鉴定了 CHS 和 CHS 样酶（命名为 MpCHS 和 MpCHSL1、2 和 3），并测定了 MpCHSL1 的晶体结构。MpCHS 催化 Claisen 缩合形成查尔酮，而 MpCHSLs 在体外催化形成内酯化的α-吡喃酮。基于结构、突变和体外生化分析，我们确定 MpCHSL1 在结构和功能上与原型 CHS 比芪合酶更接近，并确定了 III 型 PKS 功能多样性的结构基础。根据结构信息构建了 MpCHSL1 的形成查尔酮突变体。这些发现为未来阐明地钱中 III 型 PKS 的功能多样性奠定了基础。
