Fe–Ni metal clusters are crucial for energy production in many bacteria. A primary source of energy in bacteria is the oxidation and reduction of H which is performed by hydrogenase enzymes.
These enzymes are able to create a charge gradient across the cell membrane which serves as an energy store. In aerobic environments, the oxidation and reduction of oxygen is the primary energy source. However, many bacteria are capable of living in environments where O supply is limited and use H as their primary energy source . The hydrogense enzymes which provide energy to the bacteria are centered around either a Fe–Fe or Fe–Ni active site. H metabolism is not used by humans or other complex life forms, but proteins in the mitochondria of mammalian life appear to have evolved from hydrogenase enzymes, indicating that hydrogenase is a crucial step in the evolutionary development of metabolism.
The active site of Fe–Ni containing hydrogenase enzymes often is composed of one or more bridging sulfur ligands, carbonyl, cyanide and terminal sulfur ligands. The non-bridging sulfur ligands are often cystine amino acid residues that attach the active site to the protein backbone. Metal–metal bonds between the Fe and Ni have not been observed. Several oxidation states of the Fe–Ni core have been observed in a variety of enzymes, though not all appear to be catalytically relevant.
The extreme oxygen and carbon monoxide sensitivity of these enzymes presents a challenge when studying the enzymes, but many crystallographic studies have been performed. Crystal structures for enzymes isolated from D. gigas, Desulfovibrio vulgaris, Desulfovibrio fructosovorans, Desulfovibrio desulfuricans, and Desulfomicrobium baculatum  have been obtained, among others. A few bacteria, such as R. eutropha, have adapted to survive under ambient oxygen levels.
These enzymes have inspired study of structural and functional model complexes in hopes of making synthetic catalysis for hydrogen production (see Fe–Ni and hydrogen production, below, for more detail).