Groundbreaking Structural Advances in Key Catalysts for Nitrogen and Carbon Fixation: Past, Present and Future

Photosynthesis, a crucial component of the global carbon cycle, and biological nitrogen fixation (BNF), a key step in the nitrogen cycle, are both requisite for maintaining life and sustainable agriculture on Earth, in which chlorophyll and nitrogenase play central roles, respectively. In chlorophyll biosynthesis, the reduction of protochlorophyllide to chlorophyllide is catalyzed by either the nitrogenase-like, light-independent DPOR (dark-operative protochlorophyllide oxidoreductase) or the SDR-like, light-dependent LPOR (light-driven protochlorophyllide oxidoreductase), utilizing chemical and light energy. Nitrogenase (N₂ase) is the only enzyme capable of reducing inert atmospheric nitrogen, yet only a few bacterial species possess the multi-subunit ATP-dependent dinitrogen reductase. Over the past three decades, significant progress has been made in solving the crystal structures of N₂ase, DPOR, and LPOR protein complex, providing valuable mechanistic insights into N₂ase, as well as the contrasting structures of the multi-subunit DPOR and single-subunit LPOR. We summarize the structural breakthroughs of these key catalysts for nitrogen and carbon fixation. Protein structural similarities often hint at similar functions and evolutionary relationships. With the ongoing development in protein structure annotation assisted by AlphaFold and the identification of protein structure similarities through structural alignment software, the evolutionary relationship between these key enzymes in photosynthesis and nitrogen fixation, as well as the potential co-origin of these processes, has been uncovered. We further summarize how a porphyrin reduction catalyst evolves from a less efficient ATP-driven DPOR to a highly efficient light-driven LPOR. The key structural milestones achieved in N₂ase, DPOR, and LPOR research laid the groundwork for future perspectives, particularly in proposing a direction for a potential nitrogen-fixing scenario using an AI-designed LUN and photosynthesis with bacteriochlorophyll using a light-driven chlide reductase (LCOR), leading to the development of more effective forms of biological nitrogen fixation and photosynthesis.