Osmotic signaling governs sunscreen biosynthesis to safeguard desert cyanobacteria against desiccation

Abstract Mycosporine‐like amino acids (MAAs) are natural sunscreens synthesized by a wide range of organisms. Although the induction of MAA production by ultraviolet radiation is well established, the signaling pathways involved and specific functions of MAAs under other stress conditions remain poorly understood. We demonstrated that MAAs serve as effective osmoprotectants for desiccation tolerance in the desert cyanobacterium Nostoc flagelliforme. Genetic disruption of genes encoding MAA biosynthetic enzymes eliminated MAA production, resulting in elevated oxidative damage, increased lipid peroxidation, and impaired photosynthesis under dehydration. Biochemical assays revealed that MAAs stabilize proteins and scavenge reactive oxygen species, indicating dual roles as osmolytes and antioxidants. Furthermore, we identified a signaling pathway Dsp1–OrrA that mediates the osmotic induction of MAA biosynthesis. Genetic disruption of either gene of Dsp1 and OrrA abolished osmotic induction and severely reduced desiccation tolerance. Phylogenomic analysis suggests that MAA biosynthesis is an ancient trait conserved in desiccation‐tolerant cyanobacteria. This work deepens our understanding of microbial adaptation to extreme environments and provides a foundation for synthetic biology applications of MAAs.