Guo Xiaojiao, Gao Lei, Li Shiwei, Gao Jing, Wang Yuanyuan, Lv Jing, Wei Jiayi, Yang Jing, Ke Han, Ding Qi, Yang Jun, Guo Fusheng, Zhang Haowen, Lei Xiaoguang, Kang Le
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Nature. 2025 Jun 25. doi: 10.1038/s41586-025-09110-y.
Aggregation pheromone, 4-vinylanisole (4VA), is specifically released by gregarious migratory locusts, and is crucial in forming locust swarms that cause destructive plagues. Control of locust plagues relies heavily on the extensive application of chemical pesticides, which has led to severe environmental and health issues. As pheromones are primary mediators of insect communication and behaviour, exploring their biosynthesis can provide important cues to develop innovative behavioural regulators, potentially reducing the reliance on chemical pesticides. Here we resolve the biosynthesis of 4VA and behavioural responses of locusts when enzymes in the 4VA biosynthetic pathway are manipulated. The process initiates with phenylalanine derived from food plants and proceeds through three precursors: cinnamic acid, p-hydroxycinnamic acid and 4-vinylphenol (4VP). Notably, the conversion from 4VP to 4VA through methylation is unique to gregarious locusts. This step is catalysed by two crucial methyltransferases, 4VPMT1 and 4VPMT2. Guided by the X-ray co-crystal structure of 4VPMT2 bound with 4VP and S-adenosyl-L-methionine, we developed 4-nitrophenol as a substrate surrogate. We identified several chemicals that can block 4VA production by inhibiting the enzymatic activities of 4VPMT proteins, thereby suppressing locust aggregative behaviour. The findings uncover the chemical logic behind 4VA biosynthesis and pinpoint two crucial enzymes as novel targets for locust swarm management.
聚集信息素4-乙烯基苯甲醚（4VA）由群居型飞蝗特异性释放，对形成造成毁灭性蝗灾的蝗群至关重要。蝗灾控制严重依赖化学农药的广泛使用，这已导致严重的环境和健康问题。由于信息素是昆虫通讯和行为的主要调节因子，探索其生物合成可为开发创新行为调节剂提供重要线索，有望减少对化学农药的依赖。在此，我们解析了4VA的生物合成以及操纵4VA生物合成途径中的酶时蝗虫的行为反应。该过程始于源自食用植物的苯丙氨酸，并经过三种前体：肉桂酸、对羟基肉桂酸和4-乙烯基苯酚（4VP）。值得注意的是，通过甲基化将4VP转化为4VA是群居型蝗虫所特有的。这一步骤由两种关键的甲基转移酶4VPMT1和4VPMT2催化。以4VPMT2与4VP和S-腺苷-L-甲硫氨酸结合的X射线共晶体结构为指导，我们开发了4-硝基苯酚作为底物替代物。我们鉴定出几种能够通过抑制4VPMT蛋白的酶活性来阻断4VA产生的化学物质，从而抑制蝗虫的聚集行为。这些发现揭示了4VA生物合成背后的化学逻辑，并确定了两种关键酶作为蝗虫群管理的新靶点。
