<p>[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe] hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S] cluster [<cite idref="PUB00035518"/>].</p><p>The large subunit of [NiFe]-hydrogenase--as well as other nickel metalloenzymes--is synthesized as a precursor devoid of the metalloenzyme active site. This precursor then undergoes a complex post-translational maturation process that requires a number of accessory proteins [<cite idref="PUB00013568"/>, <cite idref="PUB00013569"/>].</p><p>Members of this family, which includes HypX and HoxX, have been shown to be involved in this process [<cite idref="PUB00013579"/>, <cite idref="PUB00013580"/>], and have been proposed to participate in the generation and transport of the CO and CN ligands [<cite idref="PUB00013568"/>, <cite idref="PUB00013580"/>]. Interestingly, HypX/HoxX is not present in all hydrogen-metabolizing bacteria. Furthermore, hypX deletion mutants have a reduced but detectable level of hydrogenase activity [<cite idref="PUB00013580"/>, <cite idref="PUB00013579"/>, <cite idref="PUB00013581"/>].</p><p>Members of this group have an unusual domain combination: an N-terminal formyl transferase domain and a C-terminal enoyl-CoA hydratase/isomerase domain. So far, no enzymatic reaction is known to combine N₁₀-formyltetrahydrofolate as a C1 donor and acyl-CoA as a substrate [<cite idref="PUB00013568"/>, <cite idref="PUB00013580"/>].</p><p>For more information about maturation factors/accessory proteins known to be involved in CN/CO delivery, please see <db_xref db="INTERPRO" dbkey="IPR004421"/>, which describes HypF.</p> [NiFe]-hydrogenase maturation factor, HypX/HoxX type