Sustainable production of plant-derived bioactives via genetic engineering and nanotechnology-driven approaches

As the global demand for plant-based bioactives rises, fuelled by concerns about synthetic drugs and sustainability, there is urgent need for advanced metabolic engineering solutions. Conventional extraction methods, however, are limited by low yields, seasonal variabilities and environmental impact. This review critically examines sustainable production strategies that combine the potential of CRISPR-based gene editing, nanoparticle mediated delivery systems, elicitation techniques and metabolic flux regulation to enhance the secondary metabolite production in plants. Recent advances have enabled targeted pathway redirection, achieving multi-fold increases in compounds such as artemisinin, paclitaxel and reservatol in both model and medicinal species. Nanoparticle-mediated elicitation and nano-delivery of CRISPR components further enhance metabolic flux and precise genetic alterations to boost metabolite biosynthesis. Although challenges related to biological and experimental limitations including species-specific responses, incomplete pathway elucidation and off target editing remain. Technological barriers encompass scalability constraints in bioreactors, nanoparticle aggregation, phytotoxicity and regulatory hurdles involving absence of harmonised frameworks for genome-edited and nanomaterial exposed crops for pharma use. This review offers the realistic roadmap for fusion of nanotechnology with metabolite engineering for paving the way for innovations in agriculture, pharmaceuticals and industrial biotechnology, promoting more efficient and environmentally friendly production of bioactive compounds. • CRISPR/Cas enables precise edits to boost metabolite biosynthesis. • Nanoparticles enhance enzyme activity and precursor delivery. • Metabolic flux regulation improves secondary metabolite yields. • Synthetic biology advances support scalable bioactive production. • Integration of nanotech and genetics drives sustainable innovation.