Plants, pathways and a pinch of engineering: exploring terpene alkaloid biosynthesis with a focus on steroidal glycoalkaloids

Plants produce a wide array of specialised metabolites essential for adaptation of these sessile organisms to their environment. Among these, terpene alkaloids are especially noteworthy for their valuable bioactivities. This group includes monoterpene indole alkaloids (MIAs), like the anticancer agent vinblastine, and steroidal glycoalkaloids (SGAs), which serve as defensive compounds in staple Solanum crops such as tomato and potato. Characterising the enzymes involved in terpene alkaloid biosynthesis can improve strategies for producing these metabolites and reveal the evolution of new catalytic functions. Here, we investigate the GLYCOALKALOID METABOLISM12 (GAME12) enzyme, long proposed to direct SGA biosynthesis in Solanum crops. Using in vitro and in planta approaches, we show that GAME12 is a neofunctionalised γ-aminobutyric acid (GABA) transaminase, which evolved changes in active site specificity and subcellular localisation, enabling its role in SGA biosynthesis. We also highlight GAME12's potential for driving the production of nitrogen-containing steroidal defence metabolites in plants.