Sulfur-Bridged Diiron: Key Interface in Nitrogenase and Sulfite Reductase Catalytic Cycles

Nitrogenase and sulfite reductase are key enzymes in the biogeochemical nitrogen and sulfur cycles. They both feature a sulfur-bridged diiron active site within different metal cofactor structures. However, achieving a precise definition of their catalytic mechanisms at the molecular level still remains challenging. In this work, we synthesize a bioinspired sulfur-bridged diiron model complex to elucidate the multi-electron reduction mechanisms of nitrogenase and sulfite reductase. We demonstrate that sulfite, generated from the non-physiological reductant dithionite, participates in nitrogenase catalysis in vitro and is reduced to sulfide, thereby recapitulating the function of sulfite reductase at the nitrogenase active site. These observations indicate that excess dithionite can trigger “pseudo” catalysis, potentially misleading mechanistic interpretations of nitrogen fixation and calling for a re-evaluation of the classic Lowe-Thorneley model.