Cyanobacteria dominate the foundational biological soil crusts (biocrusts) of hypersaline deserts, but how they adapt to extreme hypersaline environments remains a fundamental question. Here, we assemble the genome and investigate the adaptation of the halotolerant cyanobacterium Nostoc sp. FACHB-892, a prevalent species of the Tengger Desert. Comparative phylogenomics across 76 cyanobacterial strains from diverse habitats reveals that this desert lineage underwent a significant expansion of genes involved in photosynthesis, signal transduction, and energy metabolism. Integrated transcriptomic and metabolomic analyses under salt stress demonstrate a concentration-dependent, multi-pathway response, critically involving the accumulation of key amino acid metabolism. We identify four genes putatively central to haloadaptation exhibiting signatures of adaptive convergence. Their essential roles in salt tolerance are confirmed through functional validation in Escherichia coli. This study uncovers the coordinated genomic and metabolic mechanisms underpinning cyanobacterial resilience in one of Earth's harshest environments.
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