Biological nitrogen fixation in theory, practice, and reality: a perspective on the molybdenum nitrogenase system

Abstract

Nitrogenase is the sole enzyme responsible for the ATP‐dependent conversion of atmospheric dinitrogen into the bioavailable form of ammonia (NH3), making this protein essential for the maintenance of the nitrogen cycle and thus life itself. Despite the widespread use of the Haber–Bosch process to industrially produce NH3, biological nitrogen fixation still accounts for half of the bioavailable nitrogen on Earth. An important feature of nitrogenase is that it operates under physiological conditions, where the equilibrium strongly favours ammonia production. This biological, multielectron reduction is a complex catalytic reaction that has perplexed scientists for decades. In this review, we explore the current understanding of the molybdenum nitrogenase system based on experimental and computational research, as well as the limitations of the crystallographic, spectroscopic, and computational techniques employed. Finally, essential outstanding questions regarding the nitrogenase system will be highlighted alongside suggestions for future experimental and computational work to elucidate this essential yet elusive process.

Structural consequences of turnover-induced homocitrate loss in nitrogenase

“…Nitrogenase further serves as a model system for the study of biological metal-catalyzed enzymatic reactions. Despite its significance, the atomic basis for the mechanism is incomplete due to the transient nature of its numerous intermediate states and the challenges of working with these oxygen-sensitive proteins 7 .…”

The binding of reducible N2 in the reaction domain of nitrogenase

“…For reviews see references. [1][2][3][4][5][6][7][8][9][10][11][12][13] The active site of Mo-nitrogenase is an unprecedented cluster with the composition Fe 7 MoS 9 C(homocitrate), called FeMo-co (Fig. 1(a)).…”

What triggers the coupling of proton transfer and electron transfer at the active site of nitrogenase?

“…Nitrogenase is the enzyme that catalyses the conversion of atmospheric nitrogen to biologically incorporated ammonia. 1 The enzyme consists of two proteins, Fe-protein and MoFeprotein, that effect the overall reaction of eqn (1). The Feprotein is an Fe 4 S 4 reductase with a reaction cycle involving ATP hydrolysis, docking with the Mo-Fe protein, and transferring one electron to the MoFe-protein.…”

“…One of the significant questions posed by Threat and Rees is “Does each cycle of reduction by the Fe protein result in the coupled transfer of one proton and one electron to the FeMo-co, as typically modeled?”. 1 N 2 + 8H + + 8e − + 16ATP → 2NH 3 + H 2 + 16ADP + 16P i …”