Biological nitrogen and carbon fixation: Bridging the gap between synthetic symbioses and synthetic biology

Biological nitrogen fixation (BNF) and photosynthetic carbon fixation underpin food production and climate mitigation, yet natural systems are constrained by oxygen sensitivity, high energy demand, and inefficient catalysts. This review synthesizes advances that recast these processes as engineering targets and proposes a conceptual roadmap that bridges synthetic symbioses with the synthetic biology of enzymes and pathways. For BNF, progress spans cross-kingdom strategies—from refactoring nif gene sets and targeting nitrogenase assembly to eukaryotic organelles, to engineering plant-associated diazotrophs, rhizosphere control circuits, and emerging nodule-like microenvironments. For carbon assimilation, new-to-nature CO₂-fixation modules and photorespiratory bypasses illustrate how pathway redesign and alternative carboxylases can circumvent key Calvin–Benson–Bassham limitations, and expanding photosynthetic light capture offers additional leverage. Across these domains, we extract common design principles: (ⅰ) nitrogenase output is increasingly governed by carbon/energy supply and electron delivery as much as by oxygen protection; (ⅱ) robust function requires compartment-aware enzyme–chassis coordination, substrate channeling, and dynamic regulation using sensors and control circuits; and (ⅲ) scalable implementation may benefit from distributing metabolic labor across engineered consortia rather than forcing all functions into a single host. We discuss enabling technologies—including AI-guided protein design and directed evolution, cell-free prototyping, chassis toolkits, and materials/bioelectrochemical interfaces—that can accelerate design–build–test–learn cycles and reduce barriers to deployment. Together, these insights define a path toward integrated nitrogen and carbon fixation systems for low-emission agriculture and biomanufacturing.