摘要
甲基赤藓糖醇磷酸(methylerythritol phosphate,MEP)途径是生产萜类化合物前体异戊二烯基二磷酸(isopentenyl diphosphate,IPP)和二甲基烯丙基二磷酸(dimethylallyl diphosphate,DMAPP)必要的生化途径之一,该途径广泛存在于植物、细菌及病原体体内,而哺乳动物中不存在。MEP途径包含的7个关键酶都可以作为新型农药和医药的作用靶标。甲基赤藓糖醇磷酸胞苷酰转移酶(2-C-methyl-D-erythritol-4-phosphate cytidyltransferase,IspD)是MEP途径的第三个关键酶,它的活性位点亲脂性低,但拥有独特的变构位点,近年来引起研究人员的广泛关注。利用IspD小分子抑制剂来阻断MEP通路,从而间接地抑制萜类化合物的生成,可以造成病菌和植物的死亡,达到杀菌或除草目的。本文对IspD结构、催化机理、IspD抑制剂及其作用机制等内容进行了综述,可为以IspD作为靶标的抑制剂的筛选以及新型农药和医药的开发提供指导。
MEP(methylerythritol phosphate)pathway is one of the essential biochemical pathways for the production of the terpenoid precursors isoprenyl diphosphate(IPP)and dimethylallyl diphosphate(DMAPP),and is widespread in plants,bacteria,and pathogens,but absent in mammals.The seven key enzymes of the MEP pathway have been identified as targets for the development of novel pesticides and pharmaceuticals.2-C-methyl-D-erythritol-4-phosphate cytidyltransferase(IspD)is the third key enzyme of the MEP pathway,which has a low lipophilicity of active sites but unique allosteric sites that have attracted considerable attention from researchers in recent years.Using small molecule inhibitors of IspD to block the MEP pathway and indirectly inhibit the generation of terpenoids can cause the death of pathogens and plants to achieve the purpose of sterilization or weeding.This paper reviews the structure,mechanism,IspD inhibitors and mode of action of the IspD protease.The aim is to provide guidance for the screening of inhibitors targeting IspD and the development of novel pesticides and pharmaceuticals.
作者
王吉利
陈灿
周雅情
吴文海
孙勇
王星
陈杰
WANG Jili;CHEN Can;ZHOU Yaqing;WU Wenhai;SUN Yong;WANG Xing;CHEN Jie(College of Chemistry and Environmental Engineering,Hanjiang Normal University,Shiyan 442000,Hubei Province,China;College of Chemistry and Materials Engineering,Zhejiang A&F University,Hangzhou 311300,China;College of Forestry and Biotechnology,Zhejiang A&F University,Hangzhou 311300,China)
出处
《农药学学报》
CAS
CSCD
北大核心
2024年第4期674-691,共18页
Chinese Journal of Pesticide Science
基金
湖北省教育厅科学研究计划中青年人才(Q20223103)
湖北省自然科学基金(2022CFB854)
国家自然科学基金(32101228).
