A Self-Sacrificing N-Methyltransferase Is the Precursor of the Fungal Natural Product Omphalotin
A Self-Sacrificing N-Methyltransferase Is the Precursor of the Fungal Natural Product Omphalotin
复制标题
DOI：
10.1002/anie.201703488
复制
发表时间：
2017-08-07
影响因子：
16.6
通讯作者：
Suessmuth, Roderich D.
中科院分区：
文献类型：
--
作者：
Ramm, Sascha;Krawczyk, Bartlomiej;Suessmuth, Roderich D.
对核糖体合成和翻译后修饰肽（RiPP）的研究使人们对生物合成机制有了越来越多的了解，这些机制主要来自细菌的例子。相比之下，除鹅膏菌素和鬼笔环肽外，有关来自真菌生产商的 RiPP 的报道仍然很少。真菌环肽 omphalotin A 在肽主链上携带多个 N-甲基化，这是以前仅从非核糖体肽中得知的修饰。通过挖掘产生脐橙素的真菌基因组中的前体肽，鉴定出两个生物合成基因，其中一个编码甲基转移酶 OphMA，催化其 C 末端的自动甲基化，然后被蛋白酶 OphP 释放并环化。我们的研究结果提出了一种新的 RiPP 生物合成机制，其中修饰酶具有自己的前体肽。
Research on ribosomally synthesized and posttranslationally modified peptides (RiPPs) has led to an increasing understanding of biosynthetic mechanisms, mostly drawn from bacterial examples. In contrast, reports on RiPPs from fungal producers, apart from the amanitins and phalloidins, are still scarce. The fungal cyclopeptide omphalotin A carries multiple N-methylations on the peptide backbone, a modification previously known only from nonribosomal peptides. Mining the genome of the omphalotin-producing fungus for a precursor peptide led to the identification of two biosynthesis genes, one encoding a methyltransferase OphMA that catalyzes the automethylation of its C-terminus, which is then released and cyclized by the protease OphP. Our findings suggest a novel biosynthesis mechanism for a RiPP in which a modifying enzyme bears its own precursor peptide.