苹果蠹蛾CpGST1代谢拟除虫菊酯类杀虫剂的分子机制

谷胱甘肽转移酶（GSTs）是重要的解毒酶，参与昆虫对拟除虫菊酯杀虫剂抗药性的形成。前期研究发现，苹果蠹蛾CpGST1能结合并代谢高效氯氟氰菊酯，但其代谢拟除虫菊酯类(Pys)杀虫剂的分子机制尚不清楚。本项目以苹果蠹蛾CpGST1为研究对象，利用分子模拟的方法，探索CpGST1与8种Pys杀虫剂的结合模式、结合过程中的结构和主要能量的动态变化规律，探明互作功能域，并预测Pys的潜在代谢产物；同时，通过昆虫杆状病毒表达系统表达CpGST1重组蛋白，比较研究CpGST1重组蛋白与8种Pys的结合能力、对8种Pys的代谢能力、以及Pys的代谢产物的规律。在上述研究基础上，阐明苹果蠹蛾CpGST1与Pys类杀虫剂作用的规律，揭示苹果蠹蛾CpGST1代谢Pys类杀虫剂的分子机制。该项目的实施可为其它害虫对各类杀虫剂产生代谢抗性的分子机制研究提供新思路。

Glutathione S-transferases (GSTs), a key superfamily of detoxification enzymes, are involved in the formation of insect resistance to pyrethroid insecticides. Our previous study indicated that the lambda-cyhalothrin could be bound with and further metabolized by CpGST1 from the codling moth, Cydia pomonella. However, little is known about the molecular mechanisms of pyrethroid insecticides by CpGST1. In this project, eight different pyrethroids was chosen to explore the intermolecular universal laws of the binding modes, and the dynamic changes of the structure and main energies by reference to molecular simulation. Functional domains of interaction and the potential metabolites of Pys could also be predicted by molecular simulation. Meanwhile, the recombinant CpGST1 protein was obtained by using baculovirus expression vector system. The ability of recombinant CpGST1 to bind with and to metabolize each pyrethroids and the metabolites of each pyrethroids were comparatively studied. The relationship between the Pys structure and binding and metabolizing ability of CpGST1 was analysed. The universal laws of CpGST1 interacting with Pys, and the CpGST1-mediated pyrethroids metabolism molecular mechanism were elucidated through the combination of above research. The implementation of this project provides a new avenue for the study on molecular mechanism of metabolic resistance to various insecticides in other pests.