Molecular hydrogen (H2) plays a pivotal role in the metabolism of many microorganisms, including bacteria, archaea and lower eukaryotes. Under strictly anoxic conditions, H2 is expelled as a waste product in the course of fermentative processes. On the other hand, H2 can serve as valuable energy source if used in combination with suitable electron acceptors. Both reactions, H2 evolution by proton reduction as well as oxidation of H2 to protons and electrons, are catalyzed by complex metalloenzymes referred to as hydrogenases. In these enzymes, catalysis takes place at transition metal centers displaying a sophisticated molecular architecture.

Depending on the metal content of the active site, hydrogenases are classified into [Fe]-, [FeFe]-, and [NiFe]-hydrogenases. Besides their preferred substrate, H2, hydrogenases generally interact also with molecular oxygen (O2), which leads to the formation of (irreversibly) inactive forms of the catalytic center.