法国巴斯德研究所Simonetta Gribaldo研究团队宣布他们开发出甲烷菌水解酶揭示了古菌肽聚糖的结构。2026年9月23日出版的《自然》发表了这项成果。

肽聚糖（PG）是细菌细胞壁近乎普遍且必需的特征，也是主要的抗菌靶点。尽管古菌通常缺乏PG，但数十年前在一个主要的产甲烷古菌分支中描述了一种PG样聚合物（假胞壁质或古菌PG），然而由于缺乏专门的分析工具，对其表征仍很不充分。在此，研究人员鉴定并表征了来自Methanobrevibacter smithii（人类肠道微生物组中的优势成员）的ArmA，这是首个对古菌PG具有特异性的糖基水解酶。ArmA介导的消化揭示了一种出乎意料的结构，修正了当前古菌PG的模型。其聚糖骨架由N-乙酰葡糖胺/N-乙酰半乳糖胺与一种此前未描述的糖相连组成，研究人员将其命名为N-乙酰阿洛糖胺。聚糖链交替具有β(1,4)和β(1,3)连接，茎肽通过酰胺键连接到N-乙酰阿洛糖胺的琥珀酰基上。ArmA具有双重酶活性，既能切割糖苷键，也能切割肽交联。系统发育分析表明，ArmA同源物仅限于含PG的古菌，并且研究人员在多种产甲烷菌中证实了其活性。他们进一步证明，ArmA是完成胞质分裂所必需的，在细胞分裂位点切割古菌PG。总之，这些发现推翻了关于古菌PG结构长达50年的范式，并确立了ArmA作为一种关键工具，其影响可与细菌中的溶菌酶相媲美，使得对产甲烷菌细胞壁生物学的生化和遗传探究成为可能。最后，鉴于产甲烷菌在生态和生物技术上的重要性，研究人员的结果为靶向干预开辟了新途径。

附：英文原文

Title: A methanogen hydrolase reveals the structure of archaeal peptidoglycan

Author: Smith, Robert, Pende, Nika, Rifflet, Aline, Taib, Najwa, Witwinowski, Jerzy, Martin-Gallausiaux, Camille, Cornilleau, Charlne, Garcia, Pierre Simon, Villa, Romain, Douch, Thibaut, Matondo, Mariette, Majrouh, Manuel, Reichelt, Robert, Grohmann, Dina, Tripp, Patrick, Albers, Sonja-Verena, Borrel, Guillaume, Rittmann, Simon K.-M. R., Sartori-Rupp, Anna, Wheeler, Richard, Guijarro, J. Iaki, Boneca, Ivo Gomperts, Gribaldo, Simonetta

Issue&Volume: 2026-09-23

Abstract: Peptidoglycan (PG) is a near-universal and essential feature of bacterial cell walls and a major antimicrobial target1. Although archaea generally lack PG2, a PG-like polymer (pseudomurein or archaeal PG) was described decades ago in a major clade of methanogenic archaea3,4,5,6,7,8, yet it has remained poorly characterized, owing to the lack of dedicated analytical tools. Here we identify and characterize ArmA from Methanobrevibacter smithii, a dominant member of the human gut microbiome9, as the first glycosyl hydrolase specific for archaeal PG. ArmA-mediated digestion reveals an unexpected architecture that revises the prevailing model of archaeal PG. The glycan backbone comprises N-acetylglucosamine/N-acetylgalactosamine linked to a previously undescribed sugar, which we name N-acetylarmosamine. Glycan strands alternate β(1,4) and β(1,3) linkages, and the stem peptide is attached by means of an amide bond to the N-acetylarmosamine succinyl group. ArmA has dual enzymatic activity, cleaving both glycosidic linkages and peptide crosslinks. Phylogenetic analyses show that ArmA homologues are restricted to PG-bearing archaea, and we confirm activity across diverse methanogens. We further demonstrate that ArmA is required to complete cytokinesis, cleaving archaeal PG at the site of cell division. Together, these findings overturn a 50-year-old paradigm on archaeal PG structure and establish ArmA as a critical tool that parallels the impact of muramidases in bacteria, enabling biochemical and genetic interrogation of methanogen cell-wall biology. Finally, given the ecological and biotechnological importance of methanogens10,11, our results open new avenues for targeted intervention.

DOI: 10.1038/s41586-026-11028-y

Source: https://www.nature.com/articles/s41586-026-11028-y