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Structural snapshots of the minimal PKS system responsible for octaketide biosynthesis.
Nature Chemistry ( IF 19.2 ) Pub Date : 2020-07-06 , DOI: 10.1038/s41557-020-0491-7
Alois Bräuer 1 , Qiuqin Zhou 2 , Gina L C Grammbitter 2 , Maximilian Schmalhofer 1 , Michael Rühl 2 , Ville R I Kaila 1, 3 , Helge B Bode 2, 4, 5 , Michael Groll 1
Affiliation  

Type II polyketide synthases (PKSs) are multi-enzyme complexes that produce secondary metabolites of medical relevance. Chemical backbones of such polyketides are produced by minimal PKS systems that consist of a malonyl transacylase, an acyl carrier protein and an α/β heterodimeric ketosynthase. Here, we present X-ray structures of all ternary complexes that constitute the minimal PKS system for anthraquinone biosynthesis in Photorhabdus luminescens. In addition, we characterize this invariable core using molecular simulations, mutagenesis experiments and functional assays. We show that malonylation of the acyl carrier protein is accompanied by major structural rearrangements in the transacylase. Principles of an ongoing chain elongation are derived from the ternary complex with a hexaketide covalently linking the heterodimeric ketosynthase with the acyl carrier protein. Our results for the minimal PKS system provide mechanistic understanding of PKSs and a fundamental basis for engineering PKS pathways for future applications.



中文翻译:

负责octaketide生物合成的最小PKS系统的结构快照。

II型聚酮化合物合酶(PKSs)是多种酶复合物,可产生具有医学意义的次级代谢产物。此类聚酮化合物的化学主链是通过最小限度的PKS系统生产的,该系统由丙二酰基转酰基酶,酰基载体蛋白和α/β异二聚酮合成酶组成。在这里,我们本构成最小PKS系统,用于生物合成蒽醌所有三元复合物的X-射线结构发光光。此外,我们使用分子模拟,诱变实验和功能分析来表征这一恒定核心。我们表明,酰基载体蛋白的丙二酰化在转酰基酶中伴随着主要的结构重排。进行中的链延长的原理源自三元复合物,该复合物具有将异二聚酮合成酶与酰基载体蛋白共价连接的六酮化合物。我们对最小PKS系统的研究结果提供了对PKS的机械理解,并为将来的应用设计了PKS路径的基础。

更新日期:2020-07-06
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