Here insights were gained into the mechanisms underlying the capability of the desiccation-tolerant cyanobacterium Chroococcidiopsis sp. CCMEE 029 to overcome oxidative injury, by drawing a comparison with the oxidative-stress sensitive cyanobacterium Synechocystis sp. PCC 6803. After H₂O₂-treatment, both cyanobacteria showed no differences in non-enzymatic antioxidants, such us phenolic compounds and glutathione, while Chroococcidiopsis showed an enhanced activity of the ROS–scavenger enzymes. Both cyanobacteria have a comparable inherent glutathione peroxidase and catalase activity, while Chroococcidiopsis exhibited a higher inherent peroxidase activity. After H₂O₂ treatment Chroococcidiopsis exhibited higher enzymatic activities of the enzymes that was slightly higher in H₂O₂-treated Synechocystis. The in-silico analysis identified in Chroococcidiopsis's genome three superoxide dismutases, four catalases and five peroxidases, that shared the highest similarity with orthologs of cyanobacteria from extreme environments and that were upregulated after H₂O₂ treatment. Only one peroxidase was upregulated in H₂O₂-treated Synechocystis. Results contributed to unravel the oxidative-stress response of Chroococcidiopsis, a required knowledge for its future employment in bioprocesses to support human space exploration that are exposed to oxidative stress caused by altered gravity and cosmic radiation. © 2025 Elsevier B.V.

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