从植物中发现特异性作用靶标和先导化合物，对创制具有自主知识产权的环境友好型农药意义重大。本课题组研究证明甜菜夜蛾拓扑异构酶I （Topo I）是喜树碱类化合物的作用靶标，系统性地开展该靶标与喜树碱类抑制剂的关系研究将有利于此特异性靶标农药的研发与应用。本项目将在前期工作基础上，通过对昆虫Topo I氨基酸多型性及其对Topo I结构和功能的影响研究，确定昆虫Topo I对喜树碱类抑制剂敏感的氨基酸位点；克隆我国主要农业害虫Topo I氨基酸多型性基因片段，测定和评价其对喜树碱类抑制剂的敏感性，明确喜树碱及衍生物的防治害虫谱，促进以喜树碱为先导化合物的环境友好型特异性靶标新农药的开发；同时，利用昆虫Topo I氨基酸多型性与Topo I抑制剂的互作机制，对来自动物、植物微生物的天然化合物进行活性筛选，发现可用于防治农业害虫的Topo I抑制剂，为新农药的创制贮备更多具有发展潜力的先导化合物。

It is important to find the potential specific target and lead compounds from plants. Our previous research works indicated that DNA topoisomerase I （Topo I） from Spodoptera exigua Hübner is the target of camptothecin (CPT) and its derivates, which suggested a potential specific target for the control of insects. Researching systemically the function of Topo I and the structure-activity relationships between Topo I and its inhibitors will benefit the development and application of this specific target and its inhibitors. Based on our previous research works, we will focus on studying the effect of amino acid polymorphisms of Topo I on its structure and function, finding the sensitive polymorphic amino acid sites to CPT. According to these results, the sensitivity of the pests to CPT and its derivatives will be evaluated through cloning the genetic fragments including amino acid polymorphisms of TopoI from some important insects. Therefore, the controlling spectrum of CPT and its derivatives can be illustrated, which will provide important informations for the rational use of CPT and its derivatives, and for developing more environment-friendly insecticides based on CPT. Meanwhile, the compounds from animals, microorganisms and plant will be screened based on amino acid polymorphisms of Topo I to discovery more Topo I inhibitors, which can be used to control crop pests or to provide more potential lead compounds.