Marine Molecular Machines: Heterocyclization in Cyanobactin Biosynthesis
Marine Molecular Machines: Heterocyclization in Cyanobactin Biosynthesis
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DOI：
10.1002/cbic.201000196
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发表时间：
2010-07-05
期刊：
影响因子：
3.2
通讯作者：
Schmidt, Eric W.
中科院分区：
文献类型：
--
作者：
McIntosh, John A.;Schmidt, Eric W.
含有氨基酸衍生的（Cys、Ser、Thr）杂环的天然产物在自然界中普遍存在，但其生物合成的关键方面仍不清楚。蓝细菌素是来自蓝细菌的杂环核糖体肽天然产物，包括与海洋海鞘共生的细菌。与已研究的其他核糖体肽杂环化酶相反，蓝菌素杂环化酶是不需要氧化酶的单一蛋白质。利用这种简化条件，我们提供了新的证据来支持以下假设：这些酶是在产物结合或定向循环中使用 ATP 的分子机器。此外，我们还发现蛋白酶抑制剂和 ATP 类似物都能抑制杂环化，并确定蓝菌素生物合成途径中生化步骤的顺序。蓝菌素途径酶 PatD 和 TruD 是噻唑啉和恶唑啉合成酶。
Natural products that contain amino-acid-derived (Cys, Ser, Thr) heterocycles are ubiquitous in nature, yet key aspects of their biosynthesis remain undefined. Cyanobactins are heterocyclic ribosomal peptide natural products from cyanobacteria, including symbiotic bacteria living with marine ascidians. In contrast to other ribosomal peptide heterocyclases that have been studied, the cyanobactin heterocyclase is a single protein that does not require an oxidase enzyme. Using this simplifying condition, we provide new evidence to support the hypothesis that these enzymes are molecular machines that use ATP in a product binding or orientation cycle. Further, we show that both protease inhibitors and ATP analogues inhibit heterocyclization and define the order of biochemical steps in the cyanobactin biosynthetic pathway. The cyanobactin pathway enzymes, PatD and TruD, are thiazoline and oxazoline synthetases.