hydrogenases

Hydrogenases are enzymes that catalyze the reversible interconversion of molecular hydrogen (H2) and protons with electrons. They link hydrogen metabolism to cellular energy pathways and occur in a wide range of organisms, including bacteria, archaea, and some algae. Hydrogenases are diverse in structure and metal content, and are typically classified by their active site metals as [FeFe]-hydrogenases, [NiFe]-hydrogenases, and, less commonly, [Fe]-hydrogenases.

Two major families dominate: [FeFe]-hydrogenases and [NiFe]-hydrogenases. [FeFe]-hydrogenases possess an H-cluster active site formed by a [4Fe-4S] cluster linked to a diiron subsite with carbon monoxide and cyanide ligands, which catalyzes rapid hydrogen turnover. [NiFe]-hydrogenases contain a nickel-iron center with terminal CO and CN ligands; their redox-active site couples hydrogen oxidation or production to electron transfer chains. Many hydrogenases are sensitive to oxygen, though a subset of O2-tolerant enzymes exists in certain lineages. Enzyme maturation requires dedicated accessory proteins (maturases) that assemble and insert the metal cofactors.

Localization and reaction direction vary: hydrogenases can be cytosolic or periplasmic in bacteria and archaea. They function in hydrogen uptake, feeding electrons into respiratory or biosynthetic pathways, or in hydrogen evolution, generating H2 as a metabolic byproduct or as part of energy conservation. Some hydrogenases participate in specialized processes such as methanogenesis or syntrophic interactions in anaerobic environments.

Ecological and applied significance: Hydrogenases are central to global hydrogen cycling in anaerobic ecosystems and have attracted interest as catalysts for biohydrogen production, bioelectrochemical systems, and hydrogen sensors. Their natural diversity, including oxygen-tolerant variants, informs efforts to harness enzymatic hydrogen conversion under practical conditions.