Characterisation of lepidopteran geranylgeranyl diphosphate synthase as a putative pesticide target

IF 2.3 2区 农林科学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Evangelia Katsavou, Chara Sarafoglou, Vasileia Balabanidou, Evangelia Skoufa, Ralf Nauen, Marc Linka, Sven Geibel, Shane Denecke, John Vontas
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Abstract

Geranylgeranyl pyrophosphate (diphosphate) synthase (GGPPS) plays an important role in various physiological processes in insects, such as isoprenoid biosynthesis and protein prenylation. Here, we functionally characterised the GGPPS from the major agricultural lepidopteran pests Spodoptera frugiperda and Helicoverpa armigera. Partial disruption of GGPPS by CRISPR in S. frugiperda decreased embryo hatching rate and larval survival, suggesting that this gene is essential. Functional expression in vitro of Helicoverpa armigera GGPPS in Escherichia coli revealed a catalytically active enzyme. Next, we developed and optimised an enzyme assay to screen for potential inhibitors, such as the zoledronate and the minodronate, which showed a dose-dependent inhibition. Phylogenetic analysis of GGPPS across insects showed that GGPPS is highly conserved but also revealed several residues likely to be involved in substrate binding, which were substantially different in bee pollinator and human GGPPS. Considering the essentiality of GGPPS and its putative binding residue variability qualifies a GGPPS as a novel pesticide target. The developed assay may contribute to the identification of novel insecticide leads.

Abstract Image

鳞翅目香叶基二磷酸合成酶作为农药靶点的特性研究。
Geranylgeranyl焦磷酸(二磷酸)合成酶(GGPPS)在昆虫类异戊二烯生物合成和蛋白质烯酰化等多种生理过程中起重要作用。在此,我们对主要农业鳞翅目害虫狐尾蛾和棉铃虫的GGPPS进行了功能表征。CRISPR部分破坏GGPPS会降低S. frugiperda的胚胎孵化率和幼虫存活率,表明该基因是必不可少的。棉铃虫GGPPS在大肠杆菌中的体外功能表达显示出一种催化活性酶。接下来,我们开发并优化了一种酶分析来筛选潜在的抑制剂,如唑来膦酸盐和米诺膦酸盐,它们显示出剂量依赖性的抑制作用。昆虫GGPPS的系统发育分析表明,GGPPS具有高度保守性,但也发现了一些可能参与底物结合的残基,这些残基在蜜蜂传粉媒介和人类GGPPS中存在很大差异。考虑到GGPPS的重要性及其假定的结合残基可变性,GGPPS有资格成为一种新的农药靶标。该方法可用于新型杀虫剂铅的鉴定。
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来源期刊
Insect Molecular Biology
Insect Molecular Biology 生物-昆虫学
CiteScore
4.80
自引率
3.80%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Insect Molecular Biology has been dedicated to providing researchers with the opportunity to publish high quality original research on topics broadly related to insect molecular biology since 1992. IMB is particularly interested in publishing research in insect genomics/genes and proteomics/proteins. This includes research related to: • insect gene structure • control of gene expression • localisation and function/activity of proteins • interactions of proteins and ligands/substrates • effect of mutations on gene/protein function • evolution of insect genes/genomes, especially where principles relevant to insects in general are established • molecular population genetics where data are used to identify genes (or regions of genomes) involved in specific adaptations • gene mapping using molecular tools • molecular interactions of insects with microorganisms including Wolbachia, symbionts and viruses or other pathogens transmitted by insects Papers can include large data sets e.g.from micro-array or proteomic experiments or analyses of genome sequences done in silico (subject to the data being placed in the context of hypothesis testing).
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