title: CO2 Reduction Catalyzed by Nitrogenase: Pathways to Formate, Carbon Monoxide, and Methane.
abstract: 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 (α-70(Val→Ala), α-195(His→Gln)) are found to significantly alter the distribution of products between formate and CO/CH4.
authors: Department of Chemistry and Biochemistry, Utah State University , Logan, Utah 84322, United States.
authors: Nimesh
authors: N
authors: Khadka
authors: Department of Biochemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors: Dennis R
authors: DR
authors: Dean
authors: Intel Corporation , Hillsboro, Oregon 97124, United States.
authors: Dayle
authors: D
authors: Smith
authors: Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
authors: Brian M
authors: BM
authors: Hoffman
authors: Pacific Northwestern National Laboratory , Richland, Washington 99352, United States.
authors: Simone
authors: S
authors: Raugei
authors: Department of Chemistry and Biochemistry, Utah State University , Logan, Utah 84322, United States.
authors: Lance C
authors: LC
authors: Seefeldt
mesh_terms: D016948:Azotobacter vinelandii / Q000201:enzymology* / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism*; D005561:Formates / Q000378:metabolism*; D008697:Methane / Q000378:metabolism*; D008983:Molybdoferredoxin / Q000378:metabolism*; D009591:Nitrogenase / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D005561:Formates; D008983:Molybdoferredoxin; C030544:formic acid; D002245:Carbon Dioxide; D002248:Carbon Monoxide; D009591:Nitrogenase; D008697:Methane