[ Fe ]‐Hydrogenase and the FeGP Cofactor Involved in the CO 2 ‐Reducing Hydrogenotrophic Methanogenic Pathway

[Fe]-hydrogenase (Hmd) is involved in the hydrogenotrophic methanogenic pathway of many methanogens without cytochromes and catalyzes the heterolytic cleavage of H 2 as well as the reversible hydride transfer to methenyl-tetrahydromethanopterin. This enzyme contains the iron-guanylylpyridinol (FeGP) cofactor as a prosthetic group. The FeGP cofactor contains a unique mono-iron complex ligated with two CO molecules: a nitrogen and an acyl ligand from the pyridinol ring and a cysteine thiolate ligand of the enzyme. The proteins responsible for FeGP biosynthesis are encoded by seven hcg genes, which occur together with the gene encoding Hmd. The functions of HcgB, HcgC, HcgD, HcgE, and HcgF have been investigated by structure–function analysis. The functions of HcgA and HcgG have been studied by in vitro biosynthesis assays. Here, we review the structure and function of [Fe]-hydrogenase as well as the complex biosynthesis of the FeGP cofactor.