Multi-Omics Roadmap to Plant-Derived Medicines

Medicinal plants are invaluable sources of bioactive natural products or metabolites, however the discovery and sustainable utilization of these metabolites remain challenging. Genomic resources now provide a foundation for elucidating biosynthetic pathways that enable metabolic engineering and high-yield breeding. While genomic studies in medicinal plants have long lagged behind those on model species, next-generation sequencing has accelerated progress. Capitalizing on this genomic expansion, we systematically reviewed advancements in sequencing and assembly and analyzed more than 400 publicly available medicinal plant genomes. These resources, though variable in quality and phylogenetically biased (i.e., angiosperm-dominated), allow for multi-omics analysis of biosynthetic pathways. Single-cell RNA sequencing resolves cell-type-specific expression of biosynthetic genes, while emerging spatial transcriptomic and metabolomic techniques map metabolite distributions. Key findings reveal that small and large gene duplications drive the diversity of metabolites. Comparative genomics has identified copy number variations in critical enzyme families and divergent evolution of biosynthetic gene clusters. Further development of sustainable high-yield varieties of medicinal plants requires the integration of multi-omics technologies with systems biology for pathway refinement, enzyme engineering, and the deployment of genome-enabled molecular breeding.