Cyanobacteria can perform both anoxygenic and oxygenic photosynthesis, a characteristic which ensured that these organisms were crucial in the evolution of the early Earth and the biosphere. Reactive oxygen species (ROS) produced in oxygenic photosynthesis and reactive sulfur species (RSS) produced in anoxygenic photosynthesis are closely related to intracellular redox equilibrium. ROS comprise superoxide anion (O₂^●−), hydrogen peroxide (H₂O₂), and hydroxyl radicals (^●OH). RSS comprise H₂S and sulfane sulfur (persulfide, polysulfide, and S₈). Although the sensing mechanism for ROS in cyanobacteria has been explored, that of RSS has not been elucidated. Here, we studied the function of the transcriptional repressor PerR in RSS sensing in Synechococcus sp. PCC7002 (PCC7002). PerR was previously reported to sense ROS; however, our results revealed that it also participated in RSS sensing. PerR repressed the expression of prxI and downregulated the tolerance of PCC7002 to polysulfide (H₂S_n). The reporter system indicated that PerR sensed H₂S_n. Cys¹²¹ of the Cys4:Zn²⁺ site, which contains four cysteines (Cys¹²¹, Cys¹²⁴, Cys¹⁶⁰, and Cys¹⁶³) bound to one zinc atom, could be modified by H₂S_n to Cys¹²¹-SSH, as a result of which the zinc atom was released from the site. Moreover, Cys¹⁹ could also be modified by polysulfide to Cys¹⁹-SSH. Thus, our results reveal that PerR, a representative of the Cys₄ zinc finger proteins, senses H₂S_n. Our findings provide a new perspective to explore the adaptation strategy of cyanobacteria in Proterozoic and contemporary sulfurization oceans.

Oxygenic and anoxygenic photosynthesis have long been considered defining traits of cyanobacteria. However, whether the important cyanobacterial genus Synechococcus is capable of anoxygenic photosynthesis remains unconfirmed. Here, we report that Synechococcus sp. PCC 7002 is capable of anoxygenic photosynthesis when sulfide (H₂S) is supplied as the sole electron donor. Combining the targeted deletion of the sulfide: quinone oxidoreductase gene (Δsqr) with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) mediated the inhibition of photosystem II. We demonstrated that SQR-mediated H₂S oxidation sustains light-dependent CO₂ fixation in the absence of O₂ evolution. Our genome-wide transcriptomic profiling further revealed that polysulfide (H₂S_n) and hydrogen peroxide (H₂O₂) function as distinct signaling molecules in oxygenic and anoxygenic photosynthesis, modulating central carbon and energy metabolism. In central carbon metabolism, H₂S_n markedly upregulates the expression of key genes, including psbA, petC, rbcL, and rbcS, whereas H₂O₂ downregulates these genes. Within energy metabolism, both molecules converge on oxidative phosphorylation by upregulating genes encoding NADH dehydrogenase and ATP synthase. Furthermore, H₂Sₙ treatment uniquely induces sulfur-assimilation and ROS-detoxifying enzymes, conferring a markedly higher tolerance than H₂O₂. These findings provide direct evidence of anoxygenic photosynthesis in the genus Synechococcus and uncover a dual regulatory network that allows Synechococcus sp. PCC 7002 to balance redox homeostasis under fluctuating oxic/anoxic conditions.