直到最近,化学农药是控制农业害虫的最有效手段之一;因此,寻找农业害虫的杀虫剂目标一直是一个持续存在的问题。雌激素相关受体(ERRs)是调节动物细胞代谢和能量稳态的转录因子。家蚕对化学农药高度敏感,使其成为农药筛选和评价的理想模型。在这项研究中,我们检测到家蚕(Bombyxmori)农药代谢关键器官中的ERR表达,包括肥胖的身体和中肠。使用ChIP-seq技术,在代谢相关基因上游的2000-bp启动子区域中发现了许多与雌激素相关的反应元件,几乎都是潜在的ERR靶基因。ERR抑制剂,XCT-790和内分泌干扰物,双酚A,显著抑制ERR靶基因的表达,BmTreh-1,BmTret-1,BmPK,BmPFK,和BMHK,在蚕的脂肪体内,导致蚕幼虫化蛹困难,最终导致死亡。此外,基于通过生物膜干涉法观察到的ERR可以与XCT-790结合的澄清,预测了它的三维空间结构,使用分子对接技术,鉴定出对ERR具有更强亲和力的小分子化合物.总之,利用鳞翅目害虫ERR强大的代谢调节功能,开发的ERR小分子抑制剂可用于未来鳞翅目害虫的防治。
Until recently, chemical pesticides were one of the most effective means of controlling agricultural pests; therefore, the search for insecticide targets for agricultural pests has been an ongoing problem. Estrogen-related receptors (ERRs) are transcription factors that regulate cellular metabolism and energy homeostasis in animals. Silkworms are highly sensitive to chemical pesticides, making them ideal models for pesticide screening and evaluation. In this study, we detected ERR expression in key organs involved in pesticide metabolism in silkworms (Bombyx mori), including the fat body and midgut. Using ChIP-seq technology, many estrogen- related response elements were identified in the 2000-bp promoter region upstream of metabolism-related genes, almost all of which were potential ERR target genes. The ERR inhibitor, XCT-790, and the endocrine disruptor, bisphenol A, significantly inhibited expression of the ERR target genes, BmTreh-1, BmTret-1, BmPK, BmPFK, and BmHK, in the fat bodies of silkworms, resulting in pupation difficulties in silkworm larvae that ultimately lead to death. In addition, based on the clarification that the ERR can bind to XCT-790, as observed through biofilm interferometry, its three-dimensional spatial structure was predicted, and using molecular docking techniques, small-molecule compounds with a stronger affinity for the ERR were identified. In summary, utilizing the powerful metabolic regulatory function of ERR in Lepidoptera pests, the developed small molecule inhibitors of ERR can be used for future control of Lepidoptera pests.