Nature: Decoding 4-vinylanisole biosynthesis and pivotal enzymes in locusts

Locust plagues result in significant agricultural and ecological damage, and the current dependence on broad-spectrum chemical pesticides raises serious concerns regarding environmental sustainability and public health. In this study, we elucidated the biosynthetic pathway of the locust aggregation pheromone 4-vinylanisole (4VA). Through analysis of the crystal structure of the 4VPMT2-4VA-SAM complex, it was determined that 4-nitrophenol acts as a substrate analogue, effectively inhibiting 4VPMT enzyme activity and thereby preventing the formation of 4VA. This study revealed key enzymatic targets and lead inhibitors for intervention, establishing a molecular foundation for pheromone-based, environmentally sustainable locust control strategies and offering a viable alternative to reduce reliance on conventional chemical pesticides. • 4VA biosynthesis in locusts starts from phenylalanine derived from food plants, proceeding through cinnamic acid, p-hydroxycinnamic acid, and 4-vinylphenol, with the final methylation step unique to gregarious locusts. • Two key methyltransferases, 4VPMT1 and 4VPMT2, are identified; 4VPMT1 shows higher catalytic efficiency in converting 4-vinylphenol (4VP) to 4VA. • 4-Nitrophenol (4NP) is developed as a substrate surrogate to block 4VA production by inhibiting 4VPMT enzymes, based on the crystal structure of 4VPMT2 bound with 4VP and SAM.