Trapping the Complex Molecular Machinery of Polyketide and Fatty Acid Synthases with Tunable Silylcyanohydrin Crosslinkers
Trapping the Complex Molecular Machinery of Polyketide and Fatty Acid Synthases with Tunable Silylcyanohydrin Crosslinkers
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DOI：
10.1002/anie.201806865
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发表时间：
2018-12-21
影响因子：
16.6
通讯作者：
Burkart, Michael D.
中科院分区：
文献类型：
--
作者：
Konno, Sho;La Clair, James J.;Burkart, Michael D.
许多家族的天然产物是由大型多结构域生物机器合成的，通常被称为大合成酶。虽然基于机制的工具的进步已经为引导载体蛋白依赖性酶的蛋白质-蛋白质界面内的结构特征打开了新的窗口，但迫切需要能够以位点选择性方式连接共翻译结构域的工具。现在，使用甲硅烷基氰醇被证明在两个步骤，两个网站的选择性交联的载体蛋白质相互作用的捕获内megasynthase。这一进展提供了一种新的工具，以捕获多模块系统中的中间状态，了解脂肪酸（FAS）和聚酮（PKS）酶的特异性的关键一步。
Many families of natural products are synthesized by large multidomain biological machines commonly referred to as megasynthases. While the advance of mechanism-based tools has opened new windows into the structural features within the protein-protein interfaces guiding carrier protein dependent enzymes, there is an immediate need for tools that can be engaged to link co-translated domains in a site-selective manner. Now, the use of silylcyanohydrins is demonstrated in a two-step, two-site selective crosslinking for the trapping of carrier-protein interactions within megasynthases. This advance provides a new tool to trap intermediate states within multimodular systems, a key step toward understanding the specificities within fatty acid (FAS) and polyketide (PKS) synthases.