Multi-omics dissection of a ceRNA–PKS regulatory network underlying lead tolerance in Morchella sextelata

Heavy metal contamination severely threatens soil ecosystems and edible fungi. Comparative analyses of three Morchella species under Pb stress identified Morchella sextelata as highly tolerant, warranting further investigation. Multi-omics analyses revealed that this resilience is mediated by an integrated post-transcriptional and metabolic regulatory system. A circRNA-miRNA-mRNA (ceRNA) network functions as a molecular switch to activate the core polyketide synthase gene MsPKS, redirecting metabolic flux toward defense pathways. This activation establishes a multi-dimensional defense network comprising: an enzymatic antioxidant shield via SOD; concurrent non-enzymatic biochemical buffering involving N-acetyl-D-cysteine and dTDP-sugars; and a structural barrier formed by PKS-derived pigments that sequester Pb and mitigate oxidative damage. Through this coordinated strategy, M. sextelata maintains cellular homeostasis while prioritizing survival under severe Pb stress. This study reveals a previously unrecognized link between post-transcriptional regulation and metabolite-driven heavy metal defense, providing a mechanistic basis for fungal adaptation and bioremediation potential.