Systems-level orchestration of oxygenic photosynthesis and nitrogen fixation in cyanobacteria

SUMMARYDiazotrophic cyanobacteria represent a unique group of prokaryotes that are capable of performing two physiologically conflicting processes: oxygen-generating photosynthesis and oxygen-sensitive nitrogen fixation. Adaptive evolution over millions of years has culminated in two complex, divergent strategies-spatial and temporal separation-that allow extant cyanobacteria to reconcile these antagonistic pathways. While the long-studied spatial separation strategy utilized by most filamentous strains is well understood at the molecular level, the temporal separation mechanisms in unicellular and non-heterocystous filamentous cyanobacteria remain an expanding but under-reviewed area of research. This review focuses on the orchestration of photosynthesis and nitrogen fixation in cyanobacteria, with an emphasis on temporal separation. We discuss molecular mechanisms driving the synchronization of carbon and nitrogen fixation in filamentous cyanobacteria, highlighting recent findings that elucidate the complex regulatory networks involved in maintaining an optimal C/N balance. In contrast, for unicellular cyanobacteria, where regulatory mechanisms are less defined, we synthesize various discoveries that challenge the prevailing view that these prokaryotes are metabolically disadvantaged by strict diurnal constraints. We review studies that indicate the metabolic plasticity of these strains, potentially conferred by effective oxygen-protective mechanisms, including a robust circadian clock that regulates intracellular oxygen levels. This plasticity allows adaptation to diverse diurnal conditions, preferentially segregating the incompatible processes into opposite phases while also accommodating both processes under light when daylength conditions are suboptimal. Such metabolic flexibility likely predisposes these prokaryotes to be naturally selected for nitrogen-fixing symbioses with eukaryotes and eventually, as recently demonstrated, to evolve into a nitrogen-fixing organelle.