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. • Morchella sextelata exhibits significantly higher Pb tolerance than other Morchella species, retaining relatively higher growth rates and lower intracellular Pb accumulation under severe Pb stress (up to 1500 mg/L). • A novel ceRNA regulatory mechanism is uncovered in which MscircRNA-PKS sequesters MsmiRNA, enabling switch-like activation of the core polyketide synthase gene MsPKS under Pb stress. • Multi-omics analyses reveal an MsPKS -driven metabolic reprogramming that establishes a coordinated, multi-dimensional defense network linking post-transcriptional regulation to metabolite-mediated Pb sequestration and oxidative stress mitigation.
Liu et al. (Wed,) studied this question.