CRISPR-Cas9–Mediated Engineering of Medicinal Plants for Enhanced Phytochemical Production: Advances in Biotechnology and Therapeutic Applications
Abstract
The emergence of CRISPR-Cas9 genome editing has now broadened the scope of precise modification of genes that play a role in biosynthesis of secondary metabolites in medicinal plants. Medicinal plants generate a variety of bioactive compounds, such as alkaloids, terpenoids, phenylpropanoids, and glucosinolates, and their biosynthesis is controlled by multifaceted pathways, often comprised of multiple genes, which could be targeted for manipulation. In this narrative review, 10 years of research about the use of CRISPR-Cas9 and other genome-editing technologies for phytochemical biosynthesis modification was discussed, and their potential for improving the production of therapeutically relevant metabolites in medicinal plants was also explored. The molecular targets examined comprise components of the methylerythritol phosphate (MEP) pathway of terpenoids, of shikimate–phenylpropanoid pathway for flavonoids and lignans, the benzylisoquinoline alkaloid (BIA) pathway, and the mechanism of Cas9 gene-disruption and transcriptional regulation. Phytochemicals have been investigated and reported in their use in Hypericum perforatum (hypericin), Cannabis sativa (cannabinoids), Catharanthus roseus (vindoline and catharanthine), and Artemisia annua (artemisinin); the degree of experimental validation and demonstrated enhancement varies between compounds and plant systems. The review also highlighted the use of base and prime editing as a higher-order editing approach, multiplex editing for pathway and metabolic-flux modulation, and recently emerging applications of base and prime editing in plant metabolic engineering. The combination of CRISPR with the tools of synthetic biology and computational metabolic modelling, along with omics-guided pathway analysis, could be a key aid for the future development of precision-based phytochemical engineering and phytomedicine biotechnology.
