Engineering nitrogen-fixing symbiosis: bridging signaling and intracellular entry

Nitrogen availability is a major constraint on plant growth and agricultural productivity. Legumes and several other plant lineages circumvent this limitation by establishing symbiotic associations with nitrogen-fixing microorganisms, which convert atmospheric dinitrogen into ammonia that the host assimilates. Since root nodules were first recognized as sites of biological nitrogen fixation in the late 19th century, engineering this capacity in nonlegume crops has remained a long-standing goal. However, two key challenges remain: enabling intracellular rhizobial infection and establishing a molecular framework that supports nitrogen fixation. Recent advances in the molecular, cellular, and evolutionary mechanisms underlying root nodule symbiosis now provide a conceptual framework toward this goal. In this review, we synthesize these advances and outline staged strategies for engineering nitrogen-fixing symbiosis.