Integrated Metabolomic and Transcriptomic Analysis Reveals the Pharmacological Effects and Differential Mechanisms of Isoflavone Biosynthesis in Four Species of Glycyrrhiza

Abstract

Licorice (Glycyrrhiza L.) is a globally popular medicinal and edible plant, with nearly 30 species distributed across all continents. The usable part is primarily the root. To understand the metabolic differences among different Glycyrrhiza species, we selected four species and performed comprehensive analyses of their roots. Metabolomic profiling was conducted using UPLC-MS/MS and GC-MS, while transcriptomic analysis was carried out using RNA-sequencing. A total of 2716 metabolites were identified, including flavonoids (527 types) and terpenoids (251 types), among various other components. Subsequently, network pharmacology was employed to explore the medicinal value and potential pharmacological ingredients of these metabolites. Joint analysis of transcriptomic and metabolomic data revealed significant differences in differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) in pairwise comparisons among the four species. These differences were primarily enriched in the isoflavone pathway. Further investigation into the regulatory mechanisms of isoflavone biosynthesis in different Glycyrrhiza species identified key genes and metabolites involved in isoflavone biosynthesis. Finally, we made reasonable predictions of the potential suitable habitats for the four Glycyrrhiza species, aiming to provide new insights for the development and utilization of licorice resources. The results of this study can serve as a basis for the development and utilization of licorice and for in-depth research on the regulation of isoflavone biosynthesis in licorice.