A novel two-component system regulates shikimate pathway for thermal adaptation in Thermus thermophilus

Temperature stress is a fundamental challenge for all organisms. While two-component systems (TCSs) are known to transduce environmental signals in microbes, their role in thermal sensing remains underexplored. Here, we unveil a novel thermosensitive TCS, DhqSR, in the thermophile Thermus thermophilus HB27. We demonstrate that the histidine kinase DhqS perceives thermal cues and autophosphorylates at His327. Its cognate response regulator, DhqR, is activated through a unique tyrosine-phosphorylation mechanism: phosphorylation at a unique Tyr84 residue, rather than the canonical aspartate. This atypical DhqSR system orchestrates cellular thermoadaptation by directly regulating a key enzyme in the shikimate pathway, type II 3-dehydroquinate dehydratase (DHQase). Our findings reveal a novel molecular mechanism of temperature sensing and adaptation, providing a new paradigm for microbial environmental adaptation and offering a unique toolbox for engineering thermotolerance.