Integrated transcriptomic and metabolomic analyses reveal developmental and metabolic differences between wild and cultivated Cordyceps chanhua

Abstract Cordyceps chanhua is an entomopathogenic fungus with both edible and medicinal value. However, the molecular differences between wild and cultivated C. chanhua during developmental differentiation and functional component accumulation remain poorly understood. In this study, transcriptome sequencing, untargeted metabolomics, and integrated transcriptome–metabolome analysis were used to compare cultivated fruiting bodies and mycelia (AF and AM) with wild fruiting bodies and mycelia (WF and WM), with a focus on gene expression, metabolic reprogramming, and bioactive nucleoside accumulation during the transition from mycelia to fruiting bodies. A total of 1,000 differentially expressed genes and 370 differentially accumulated metabolites were identified in AF vs AM, whereas 1,080 differentially expressed genes and 602 differentially accumulated metabolites were detected in WF vs WM, indicating extensive transcriptional and metabolic remodeling during developmental transition. In cultivated samples, the differential metabolites were mainly associated with amino acid metabolism, membrane lipid remodeling, and secondary metabolism. In contrast, those in wild samples were more closely related to glutathione metabolism, central carbon metabolism, and redox regulation. Integrated transcriptome–metabolome analysis further showed stronger correlations between differentially expressed genes and metabolites in cultivated samples, forming relatively compact functional modules. By contrast, wild samples exhibited a more dispersed gene–metabolite association pattern, suggesting distinct developmental and metabolic regulatory features under different growth environments. Functional component analysis showed that N 6 -(2-hydroxyethyl)adenosine (HEA) was significantly enriched in mycelia, whereas adenosine accumulated preferentially in cultivated fruiting bodies, indicating stage-dependent accumulation of bioactive nucleosides. Overall, this study reveals developmental differentiation, metabolic reprogramming, and bioactive nucleoside accumulation differences between wild and cultivated C. chanhua . These findings provide multi-omics evidence for understanding quality formation in C. chanhua , optimizing cultivation conditions, and developing high-quality functional food ingredients.