Application of Metabolomics in the Exploration of Bioactive Compounds and Drug Development from Medicinal Fungi

Medicinal fungi are important sources of natural medicines and are rich in a wide range of secondary metabolites with significant bioactivities, including terpenoids and alkaloids. As one of the core tools of systems biology, metabolomics has developed from simple metabolite detection into a key approach for understanding the complex life processes and medicinal value of medicinal fungi. This review summarizes recent advances in the application of metabolomics to the discovery of bioactive compounds from medicinal fungi, the optimization of cultivation and extraction processes, the analysis of pharmacological mechanisms, and the improvement of drug delivery strategies. The main methods used in metabolomics are outlined, with emphasis on the key steps of sample preparation, data acquisition, and data analysis. The review then describes how metabolomics can be used for the rapid discovery of bioactive compounds in medicinal fungi. It further explains how metabolomics can guide the precise optimization of fermentation parameters and the improvement of extraction processes by revealing the effects of environmental factors, such as light, temperature, pH, and inducers, as well as different extraction methods, on metabolic networks. In addition, this review summarizes the role of metabolomics in clarifying the molecular mechanisms by which bioactive compounds exert pharmacological effects through the modulation of specific metabolic pathways, as well as its application in optimizing dose, formulation, and route of administration. Representative studies have demonstrated that integrated metabolomic and proteomic analyses have revealed the preferential accumulation of triterpenoids, sterols, and polyphenolic compounds during the budding stage of Ganoderma lucidum. Finally, future studies should integrate metabolomics with genomics, transcriptomics, proteomics, and other omics approaches to link bioactive metabolites with their biosynthetic genes, regulatory networks, and molecular targets. In such an integrated framework, metabolomics can serve as a phenotype-oriented core for the discovery and functional characterization of therapeutic metabolites from medicinal fungi, although further experimental and clinical validation remains essential.