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Cryptic phosphorylation in nucleoside natural product biosynthesis
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2020-11-30 , DOI: 10.1038/s41589-020-00656-8
Matthew M Draelos 1 , Anyarat Thanapipatsiri 2 , Hilda Sucipto 2 , Kenichi Yokoyama 1, 2
Affiliation  

Kinases are annotated in many nucleoside biosynthetic gene clusters but generally are considered responsible only for self-resistance. Here, we report an unexpected 2′-phosphorylation of nucleoside biosynthetic intermediates in the nikkomycin and polyoxin pathways. This phosphorylation is a unique cryptic modification as it is introduced in the third of seven steps during aminohexuronic acid (AHA) nucleoside biosynthesis, retained throughout the pathway’s duration, and is removed in the last step of the pathway. Bioinformatic analysis of reported nucleoside biosynthetic gene clusters indicates the presence of cryptic phosphorylation in other pathways and the importance of functional characterization of kinases in nucleoside biosynthetic pathways in general. This study also functionally characterized all of the enzymes responsible for AHA biosynthesis and revealed that AHA is constructed via a unique oxidative C–C bond cleavage reaction. The results indicate a divergent biosynthetic mechanism for three classes of antifungal nucleoside natural products.



中文翻译:

核苷天然产物生物合成中的隐性磷酸化

激酶在许多核苷生物合成基因簇中都有注释,但通常被认为只对自抗性负责。在这里,我们报告了尼可霉素和多恶素途径中核苷生物合成中间体的意外 2'-磷酸化。这种磷酸化是一种独特的隐蔽修饰,因为它在氨基己糖醛酸 (AHA) 核苷生物合成过程中的七个步骤中的第三个步骤中引入,在整个途径的持续时间中保留,并在途径的最后一步中被去除。对已报道的核苷生物合成基因簇的生物信息学分析表明,在其他途径中存在隐蔽的磷酸化,以及一般核苷生物合成途径中激酶功能表征的重要性。该研究还在功能上表征了负责 AHA 生物合成的所有酶,并揭示 AHA 是通过独特的氧化 C-C 键裂解反应构建的。结果表明三类抗真菌核苷天然产物的生物合成机制不同。

更新日期:2020-12-01
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