Diverse lineages and adaptations of oxygen-adapted hydrogenases

Hydrogenases allow microorganisms to consume and produce hydrogen gas (H₂). Although most hydrogenases are oxygen (O₂)-sensitive, recent studies show that bacteria and archaea produce diverse nickel-iron [NiFe]-hydrogenases that function in oxic environments and often support aerobic respiration. As we describe herein, these hydrogenases have independently evolved multiple strategies to withstand O₂, not only by reversing inhibition through reduction of bound O₂ to water using a unique [4Fe3S] cluster but also by preventing O₂ binding through narrow gas channels and active-site rearrangements. We further propose that [NiFe]-hydrogenases originated on an anoxic Earth, but diversified after the Great Oxygenation Event to tolerate and exploit redox coupling with O₂. Hydrogenases may be more adaptable to O₂ than was previously thought, and this has implications for synthetic biology and biomimetics.