Towards establishing functional nitrogenase activities within plants.

Biological nitrogen fixation, catalyzed by nitrogenase, can convert atmospheric N₂ into NH₃ for plant growth. Legumes form symbioses with nitrogen-fixing bacteria, but non-legumes rely on excessive nitrogen fertilizers. Efforts to engineer nitrogenase in non-legumes face major challenges, including oxygen sensitivity, metal cluster assembly complexity, and high energy demands. Nonetheless, advances in synthetic biology, and artificial intelligence (AI)-driven design - shown by partial nitrogenase reconstitution in Escherichia coli and yeast - offer promising solutions. Engineering nitrogenase in yeast mitochondria under low-oxygen conditions also helps circumvent oxygen constraints. Fully overcoming energy costs and feedback loops responsive to nitrogen levels could yield nitrogen-fixing crops, transforming sustainable agriculture and ensuring global food security. Such breakthroughs would reduce fertilizer dependence, cut pollution, and stabilize yields in diverse farming systems.