Thermophilic cyanobacteria are key models for thermotolerance and a promising source of thermophilic bioresources. Yet the subcellular basis of their stress resilience remains poorly resolved. Here, we focus on intracellular polyphosphate (polyP)-rich granules, termed “stabilisomes,” which have been implicated in stress adaptation. The lack of a high-purity, structure-preserving isolation method has been a major technical bottleneck hindering the elucidation of this resilience mechanism. This study describes a robust, structure-preserving purification strategy, boosting the granule-to-protein yield by over 10,000-fold compared with conventional methods. The specificity and structural integrity of this method are supported by the specific enrichment of complex proteomic (937 proteins) and metabolomic (1076 metabolites) signatures. Building on this, subsequent quantitative analysis across cyanobacteria at 7 hot spring sampling sites revealed a conserved core chemical composition dominated by polyphosphate (~21–36%), proteins (~10–20%), amino acids (~7–18%), and lipid components (~12–21%). The variability in abundance across species suggests a dynamic adjustment of these stabilizing components consistent with specific micro-environmental conditions. This work provides a robust bioseparation platform for prokaryotic organelles, offering a critical tool for investigating cyanobacterial resilience and developing novel biomaterials.
Wang et al. (Thu,) studied this question.