CO2 Reduction Catalyzed by Nitrogenase: Pathways to Formate, Carbon Monoxide, and Methane. Academic Article uri icon


  • The reduction of N2 to NH3 by Mo-dependent nitrogenase at its active-site metal cluster FeMo-cofactor utilizes reductive elimination of Fe-bound hydrides with obligatory loss of H2 to activate the enzyme for binding/reduction of N2. Earlier work showed that wild-type nitrogenase and a nitrogenase with amino acid substitutions in the MoFe protein near FeMo-cofactor can catalytically reduce CO2 by two or eight electrons/protons to carbon monoxide (CO) and methane (CH4) at low rates. Here, it is demonstrated that nitrogenase preferentially reduces CO2 by two electrons/protons to formate (HCOO(-)) at rates >10 times higher than rates of CO2 reduction to CO and CH4. Quantum mechanical calculations on the doubly reduced FeMo-cofactor with a Fe-bound hydride and S-bound proton (E2(2H) state) favor a direct reaction of CO2 with the hydride ("direct hydride transfer" reaction pathway), with facile hydride transfer to CO2 yielding formate. In contrast, a significant barrier is observed for reaction of Fe-bound CO2 with the hydride ("associative" reaction pathway), which leads to CO and CH4. Remarkably, in the direct hydride transfer pathway, the Fe-H behaves as a hydridic hydrogen, whereas in the associative pathway it acts as a protic hydrogen. MoFe proteins with amino acid substitutions near FeMo-cofactor (-70(ValAla), -195(HisGln)) are found to significantly alter the distribution of products between formate and CO/CH4.

published proceedings

  • Inorg Chem

altmetric score

  • 1.85

author list (cited authors)

  • Khadka, N., Dean, D. R., Smith, D., Hoffman, B. M., Raugei, S., & Seefeldt, L. C.

citation count

  • 38

complete list of authors

  • Khadka, Nimesh||Dean, Dennis R||Smith, Dayle||Hoffman, Brian M||Raugei, Simone||Seefeldt, Lance C

publication date

  • September 2016