Engineering nitrogen and carbon fixation for next-generation plants

Improving plant nitrogen (N) and carbon (C) acquisition and assimilation is a major challenge for global agriculture, food security, and ecological sustainability. Emerging synthetic biology techniques, including directed evolution, artificial intelligence (AI)-guided enzyme design, and metabolic engineering, have opened new avenues for optimizing nitrogenase to fix atmospheric N₂ in plants, engineering Rhizobia or other nitrogen-fixing bacteria for symbiotic associations with both legume and nonlegume crops, and enhancing carbon fixation to improve photosynthetic efficiency and source-to-sink assimilate fluxes. Here, we discuss the potential for engineering nitrogen fixation and carbon fixation mechanisms in plants, from rational and AI-driven optimization of nitrogen and carbon fixation cycles. Furthermore, we discuss strategies for modifying source-to-sink relationships to promote robust growth in extreme conditions, such as arid deserts, saline-alkaline soils, or even extraterrestrial environments like Mars. The combined engineering of N and C pathways promises a new generation of crops with enhanced productivity, resource-use efficiency, and resilience. Finally, we explore future perspectives, focusing on the integration of enzyme engineering via directed evolution and computational design to accelerate metabolic innovation in plants.