Key players in plant defense: How scaffold protein GAME15 orchestrates the biosynthesis of steroidal defense metabolite

GAME15, a scaffold protein, orchestrates the biosynthesis of steroidal glycoalkaloids (a class of compounds with known defensive properties) and steroidal saponins (which contribute to plant defense) in Solanaceae plants, essential for their defense mechanisms. By assembling key enzymes at the endoplasmic reticulum, GAME15 ensures efficient metabolite production, preventing toxic intermediate diffusion. This breakthrough in plant defense biosynthesis opens opportunities for metabolic engineering, enabling the production of valuable metabolites in non-native hosts and offering potential strategies for crop protection, reducing the need for chemical pesticides. • GAME15 regulates the biosynthesis of steroidal defense metabolites in Solanaceae plants. • Loss of GAME15 increases plant susceptibility to pests. • GAME15 enables reconstitution of high-value metabolite production in non-native systems.