MULTI-OMICS-ENABLED BREEDING OF MEDICINAL PLANTS FOR ENHANCED SECONDARY METABOLITE PRODUCTION

Medicinal plants produce a bounty of biologically active secondary metabolites with their biosynthesis having been regulated by highly complex genomic and transcriptional systems.The combination of genomics, transcriptomics, proteomics, metabolomics and spatial omics has radically changed our ability to read these architectures giving a system-wide view of specialized metabolism, a gene-to-metabolite perspective.The landmark progress has provided high-quality genome assemblies in more than 400 medicinal species and chromosome-level and telomere-to-telomere (T2T) assemblies have hastened the identification of biosynthetic gene clusters (BGCs) to high-value compounds including artemisinin, morphine, vinblastine, tanshinones and monoterpenoids such as thymol and carvacrol.Multi-omics studies have revealed how expansions of gene families in terpene synthase (TPS) and cytochrome P450 (CYP) families are the main drivers of metabolite diversification, and the role of cell-type-specific metabolite pathway compartmentalization has been solved with single-cell RNA sequencing previously with previously unresolved precision.The case studies in various medicinal genera such as Fritillaria, Uncaria, Cornus, Mosla, Origanum, and Catharanthus demonstrate how combined transcriptomic and metabolomic data can be used to discover important biosynthetic enzymes and master regulatory transcription factors with direct breeding features.However, there are still major gaps, such as a strong phylogenetic bias in favor of angiosperms, lack of functional validation platforms of recalcitrant non-model species and absence of standardized metabolite phenotyping protocols of field-based breeding programs.The interplay of single-cell omics, pathway prediction with the help of artificial intelligence, Alpha Fold-enabled enzyme engineering, and genome-enabled molecular breeding is set to speed up creation of a high-yielding medicinal plant species with the potential to grow with the rising global pharmaceutical demand.