Biosynthesis of selenium-containing small molecules in diverse microorganisms
Biosynthesis of selenium-containing small molecules in diverse microorganisms
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DOI：
10.1038/s41586-022-05174-2
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发表时间：
2022-09-07
期刊：
影响因子：
64.8
通讯作者：
Seyedsayamdost, Mohammad R.
中科院分区：
文献类型：
--
作者：
Kayrouz, Chase M.;Huang, Jonathan;Seyedsayamdost, Mohammad R.
硒是多种生物体必需的微量营养素。已知其插入蛋白质和核酸的两种途径，分别通过硒代半胱氨酸和2-硒尿苷（1）。然而，尽管硒的重要性，具体纳入小分子的途径仍然难以捉摸。在这里，我们在各种微生物中使用基因组挖掘策略来揭示一个广泛的三基因簇，该基因簇编码用于生产硒酮的专用途径，硒酮是多功能分子麦角硫因的硒类似物（2，3）。我们阐明了所有这三种蛋白质的反应，并发现了两种新的硒-碳键形成酶和硒糖的生物合成途径，硒糖是一种意想不到的中间体，可以通往最终产品。我们的研究结果扩大了生物硒利用的范围，表明硒代谢组比以前认为的更多样化，并为发现其他含硒天然产物奠定了基础。
Selenium is an essential micronutrient in diverse organisms. Two routes are known for its insertion into proteins and nucleic acids, via selenocysteine and 2-selenouridine, respectively(1). However, despite its importance, pathways for specific incorporation of selenium into small molecules have remained elusive. Here we use a genome-mining strategy in various microorganisms to uncover a widespread three-gene cluster that encodes a dedicated pathway for producing selenoneine, the selenium analogue of the multifunctional molecule ergothioneine(2,3). We elucidate the reactions of all three proteins and uncover two novel selenium-carbon bond-forming enzymes and the biosynthetic pathway for production of a selenosugar, which is an unexpected intermediate en route to the final product. Our findings expand the scope of biological selenium utilization, suggest that the selenometabolome is more diverse than previously thought, and set the stage for the discovery of other selenium-containing natural products.