Nitrogenase enzymes are crucial for converting nitrogen into a form that living organisms can use, similar to the industrial Haber-Bosch process. These enzymes come in three flavors: molybdenum-based, vanadium-based, and iron-only nitrogenase. Each type is named after the metal at the core of its catalytic cofactor, Fe(M)co (M = Mo, V, and Fe). Although named for its ability to affect nitrogen fixation, a biological analogue to the Haber-Bosch process, the “alternative nitrogenase” FeFeco has recently been reported to fully reduce carbon dioxide to methane, which is inaccessible in the extensively studied FeMoco. Despite their divergent reactivities, it was widely believed that all nitrogenases share the same catalytic mechanism.
Dr. Justin P. Joyce, an Alexander von Humboldt Fellow in the Inorganic Spectroscopy Department at the MPI CEC, together with Dr. Ragnar Bjornsson (CEA-Grenoble) and Prof. Serena DeBeer (MPI CEC), uncovered drastic differences in the mechanistic pathways within the nitrogenase family. Using advanced computer simulations known as quantum mechanical/molecular mechanical (QM/MM) calculations, they compared FeMoco and FeFeco. Their findings revealed significant differences in the initial steps of their catalytic processes, which they attribute to the distinct electronic properties of the metals involved. These computational results align with previous experimental studies, offering new insights into how these enzymes function.
This research underscores the importance of understanding the electronic structure of nitrogenase enzymes to explain their varied reactions. The study, published in the Journal of the American Chemical Society, is openly accessible and provides a fresh perspective on the mechanisms of these biologically important enzymes.
Lead Authors: Ragnar Bjornsson and Serena DeBeer
Original Paper: Justin P. Joyce, Ragnar Bjornsson and Serena DeBeer. Unravelling Catalytic Divergence in Mo- and Fe-Only Nitrogenases: The Role of the Heterometal-Site and Protein Environment from QM/MM Insights. (2025) Journal of the American Chemical Society, 147, 48416-48426. DOI: 10.1021/jacs.5c20796.