Abstract

Gerronema lapidescens, a rare medicinal fungus with historical use in treating intestinal parasitosis, faces severe depletion of its wild resources because artificial domestication has not yet been achieved. This study employed integrated transcriptomic and metabolomic analyses to investigate molecular mechanisms underlying sclerotium development and bioactive compound biosynthesis in strain QL01 . Comparative analysis between mycelium and sclerotium tissues revealed 5,823 differentially expressed genes and 150 differentially accumulated metabolites. Joint pathway enrichment demonstrated significant activation of taurine/hypotaurine metabolism and sphingolipid metabolism in sclerotia, with concomitant accumulation of taurocholic acid, phytosphingosine and other sphingoid bases, indicating their crucial roles in oxidative-stress resistance and dormancy adaptation. Concurrently, polyketide synthase (PKS), O-methyltransferase and MAPK-cascade gene families were significantly up-regulated in sclerotia. Notably, phthalate esters—particularly dimethyl phthalate, a known insecticidal compound—showed sclerotium-specific accumulation. Multi-omics correlation analyses, including O2PLS-DA and weighted gene co-expression network analysis, nominated a set of candidate PKS and O-methyltransferase genes that may mediate phthalate-ester biosynthesis. This research constitutes the first comprehensive multi-omics characterisation of G. lapidescens sclerotium development, elucidating molecular correlations between developmental processes and medicinal component formation. The findings provide a set of candidate molecular targets and a preliminary mechanistic framework that may guide future efforts toward artificial domestication and sustainable utilisation of this rare medicinal resource, while supporting follow-up work on agricultural bio-control applications.