Unlocking secrets of nature's chemists: Potential of CRISPR/Cas-based tools in plant metabolic engineering for customized nutraceutical and medicinal profiles.

Plant species have evolved diverse metabolic pathways to effectively respond to internal and external signals throughout their life cycle, allowing adaptation to their sessile and phototropic nature. These pathways selectively activate specific metabolic processes, producing plant secondary metabolites (PSMs) governed by genetic and environmental factors. Humans have utilized PSM-enriched plant sources for millennia in medicine and nutraceuticals. Recent technological advances have significantly contributed to discovering metabolic pathways and related genes involved in the biosynthesis of specific PSM in different food crops and medicinal plants. Consequently, there is a growing demand for plant materials rich in nutrients and bioactive compounds, marketed as "superfoods". To meet the industrial demand for superfoods and therapeutic PSMs, modern methods such as system biology, omics, synthetic biology, and genome editing (GE) play a crucial role in identifying the molecular players, limiting steps, and regulatory circuitry involved in PSM production. Among these methods, clustered regularly interspaced short palindromic repeats-CRISPR associated protein (CRISPR/Cas) is the most widely used system for plant GE due to its simple design, flexibility, precision, and multiplexing capabilities. Utilizing the CRISPR-based toolbox for metabolic engineering (ME) offers an ideal solution for developing plants with tailored preventive (nutraceuticals) and curative (therapeutic) metabolic profiles in an ecofriendly way. This review discusses recent advances in understanding the multifactorial regulation of metabolic pathways, the application of CRISPR-based tools for plant ME, and the potential research areas for enhancing plant metabolic profiles.