Institut für Chemie, Strasse des 17. Juni 124, 10623, Berlin, Germany.
Angew Chem Int Ed Engl. 2017 Aug 7;56(33):9994-9997. doi: 10.1002/anie.201703488. Epub 2017 Jul 17.
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.
对核糖体合成和翻译后修饰肽（RiPPs）的研究加深了人们对生物合成机制的理解，这些机制主要来自于细菌的例子。相比之下，真菌产生 RiPPs 的报道仍然很少，除了鹅膏蕈碱和鬼笔环肽。真菌环肽欧泊菌素 A 在肽骨架上带有多个 N-甲基化修饰，这种修饰以前只在非核糖体肽中被发现。对产生欧泊菌素 A 的真菌基因组进行挖掘，寻找前体肽，导致了两个生物合成基因的鉴定，其中一个编码甲基转移酶 OphMA，它催化其 C 末端的自动甲基化，然后由蛋白酶 OphP 释放并环化。我们的发现表明，一种 RiPP 的生物合成机制具有新颖性，其中一种修饰酶带有其自身的前体肽。
