美国普林斯顿大学Seyedsayamdost Mohammad R.团队报道，生物合成指导下的发现显示肠肽作为含有n -甲基甲鸟氨酸的替代肽。相关研究成果发表在2022年10月31日出版的《自然—化学》。

下一代DNA测序技术和生物信息学的结合使天然产物的发现焕发新机。

使用生物信息学搜索策略，研究人员最近在被忽视的链球菌中鉴定了约600个基因簇，这些基因簇编码由自由基S-腺苷蛋氨酸酶合成的核糖体肽天然产物。这些被分为16个亚科，并指出了一个尚未探索的微生物组生物合成景观。

该文中，研究人员报道了这些天然产物其中一种的结构、生物合成和功能。它被称为肠肽，来自肠道微生物肠球菌。研究人员展示了肠肽生物合成中的三个反应，每个反应都由不同的金属酶家族催化。其中，研究人员描述了广泛存在的含Fe–S的甲基转移酶超家族的创始成员，该家族与Mn²⁺依赖性精氨酸酶一起在肽序列中安装N-甲基鸟氨酸。对成熟产品的生物测定表明，仅对生产菌株具有抑菌活性，这扩展了微生物群中自相残杀或自我抑制代谢物的新方向。

附：英文原文

Title: Biosynthesis-guided discovery reveals enteropeptins as alternative sactipeptides containing N-methylornithine

Author: Clark, Kenzie A., Covington, Brett C., Seyedsayamdost, Mohammad R.

Issue&Volume: 2022-10-31

Abstract: The combination of next-generation DNA sequencing technologies and bioinformatics has revitalized natural product discovery. Using a bioinformatic search strategy, we recently identified ～600 gene clusters in otherwise overlooked streptococci that code for ribosomal peptide natural products synthesized by radical S-adenosylmethionine enzymes. These grouped into 16 subfamilies and pointed to an unexplored microbiome biosynthetic landscape. Here we report the structure, biosynthesis and function of one of these natural product groups, which we term enteropeptins, from the gut microbe Enterococcus cecorum. We show three reactions in the biosynthesis of enteropeptins that are each catalysed by a different family of metalloenzymes. Among these, we characterize the founding member of a widespread superfamily of Fe–S-containing methyltransferases, which, together with an Mn2+-dependent arginase, installs N-methylornithine in the peptide sequence. Biological assays with the mature product revealed bacteriostatic activity only against the producing strain, extending an emerging theme of fratricidal or self-inhibitory metabolites in microbiome firmicutes.

DOI: 10.1038/s41557-022-01063-3

Source: https://www.nature.com/articles/s41557-022-01063-3