近日，德国马尔堡菲利普斯大学Jan M. Schuller团队报道了I类产甲烷菌8 MDa Hdr-Vhu-Fwd超组装体的结构。2026年7月8日出版的《自然》杂志发表了这项成果。

产甲烷菌是全球碳循环的核心参与者，也是强效温室气体甲烷最大的生物来源之一。其能量代谢的核心是Hdr–Vhu–Fwd超组装体，该复合体通过基于黄素的电子分叉机制将H₂氧化与CO₂还原相耦合。

研究组报道了来自褐藻甲烷球菌（Methanococcus maripaludis）的Hdr–Vhu–Fwd超组装体的冷冻电镜结构，揭示了一个包含252条多肽链和超过600个氧化还原辅因子的8 MDa复合物。冷冻电子断层扫描进一步支持该超组装体在完整细胞的细胞质中形成完整结构。该结构由两个六聚体HdrABC–Vhu环通过一个四聚体FwdF核心连接而成，形成连续的环形电子传递链。在这一独特排列中，12个多聚铁氧还蛋白亚基（VhuB）连接Vhu–Hdr和Fwd复合物，从而将电子分叉与CO?还原偶联起来，并直接连接了产甲烷途径的最后一步与第一步。

此外，研究组还鉴定出该复合物的一个模块化变体，其中[NiFe]氢化酶Vhu被含钨甲酸脱氢酶（FdhAB）所替代，表明电子输入模块的灵活整合有助于在不同环境条件下实现代谢适应。分类分布分析表明，这种结构为I类产甲烷菌所特有，且不同于II类中较小的Hdr–Fmd复合物。总体而言，该研究揭示了Hdr–Vhu–Fwd超组装体具有模块化且可适应的生物能量组装方式，提示其谱系特异性结构有助于适应多样的厌氧生态位。

附：英文原文

Title: Architecture of the 8 MDa Hdr–Vhu–Fwd super-assembly in class I methanogens

Author: Paul, Sophia, Pascoa, Tomas C., Klamke, Max A., Bohn, Stefan, Abendroth, Frank, Deobald, Darja, Vzquez, Olalla, Stripp, Sven T., Schuller, Jan M.

Issue&Volume: 2026-07-08

Abstract: Methanogens are central to global carbon cycling and among the largest biological sources of methane, a potent greenhouse gas1. At the heart of their energy metabolism lies the Hdr–Vhu–Fwd super-assembly, which couples H2 oxidation with CO2 reduction through flavin-based electron bifurcation. Here we present the cryogenic electron microscopy structure of the Hdr–Vhu–Fwd super-assembly from Methanococcus maripaludis, revealing an 8MDa complex comprising 252 polypeptide chains and over 600 redox cofactors. Cryo-electron tomography further support that this super-assembly forms an intact structure within the cytoplasm of intact cells. This architecture comprises two hexameric HdrABC–Vhu rings linked by a tetrameric FwdF core, forming a continuous, circular electron chain. In this unique arrangement, 12 polyferredoxin subunits (VhuB) connect the Vhu–Hdr and Fwd complexes, thereby coupling electron bifurcation with CO2 reduction and directly linking the last and the first step of methanogenesis. Moreover, we identify a modular variant of the complex in which the [NiFe]-hydrogenase Vhu is substituted by tungsten-containing formate dehydrogenase (FdhAB), indicating flexible integration of electron-input modules facilitating metabolic adaptation under diverse environmental conditions2. Analysis of the taxonomic distribution reveals that this architecture is specific to class I methanogens and is distinct from the smaller Hdr–Fmd complex of class II3. Together, our study reveals that the the Hdr–Vhu–Fwd super-assembly has a modular and adaptable bioenergetic assembly, suggesting a lineage-specific architecture to adapt to diverse anaerobic niches.

DOI: 10.1038/s41586-026-10744-9

Source: https://www.nature.com/articles/s41586-026-10744-9