Sawers R Gary, Hardelt Maximilian, Haase Alexander, Lubek Dorothea
Institute for Microbiology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Metallomics. 2025 Jun 3;17(6). doi: 10.1093/mtomcs/mfaf015.
The large subunit of all [NiFe]-hydrogenases in bacteria and archaea has a heterobimetallic NiFe(CN)2CO cofactor coordinated by four cysteine residues. The iron ion has two cyanides and a carbon monoxide as diatomic ligands. Six ancillary Hyp (ABCDEF) proteins are necessary for anaerobic synthesis of this cofactor, while under oxic conditions at least one further protein, HypX, is required for CO synthesis. The Fe(CN)2CO moiety of the cofactor is synthesized on a separate HypCD scaffold complex. Nickel is inserted into the apo-large subunit only after Fe(CN)2CO has been introduced. Recent biochemical and structural studies have significantly advanced our understanding of cofactor biosynthesis for these important metalloenzymes. Despite these gains in mechanistic insight, many questions still remain, the most pressing of which is the origin of the CO ligand in anaerobic microorganisms. This minireview provides an overview of the current status of this research field and highlights recent advances and unresolved issues.
细菌和古菌中所有[NiFe]氢化酶的大亚基都有一个由四个半胱氨酸残基配位的异双金属NiFe(CN)₂CO辅因子。铁离子有两个氰化物和一个一氧化碳作为双原子配体。六种辅助Hyp（ABCDEF）蛋白是该辅因子厌氧合成所必需的，而在有氧条件下，CO合成至少还需要一种蛋白HypX。辅因子的Fe(CN)₂CO部分在一个单独的HypCD支架复合物上合成。只有在引入Fe(CN)₂CO后，镍才会插入脱辅基大亚基中。最近的生化和结构研究极大地推进了我们对这些重要金属酶辅因子生物合成的理解。尽管在机理认识上有这些进展，但仍有许多问题存在，其中最紧迫的是厌氧微生物中CO配体的来源。本综述概述了该研究领域的现状，并突出了最近的进展和未解决的问题。
