新型杀菌剂喹诺芬林对真菌二氢乙酸脱氢酶的选择性优于相应的人酶。

IF 1.5 4区 农林科学 Q2 ENTOMOLOGY Journal of Pesticide Science Pub Date : 2023-02-20 DOI:10.1584/jpestics.D22-035
Norikazu Higashimura, Akira Hamada, Shinichi Banba
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引用次数: 0

摘要

研究了喹诺菲林靶酶2类二氢羟酸脱氢酶(DHODH)的物种选择性。为了比较喹诺菲林对真菌和哺乳动物的选择性,建立了智人DHODH (HsDHODH)检测系统。喹诺菲林对稻瘟霉DHODH (PoDHODH)和HsDHODH的IC50值分别为2.8 nM和>100µM。喹诺菲林对真菌的选择性高于人DHODH。此外,我们构建了重组稻瘟病菌突变体,将PoDHODH (PoPYR4)或HsDHODH插入到PoPYR4断裂突变体中。在0.01 ~ 1 ppm的喹诺菲林浓度下,PoPYR4插入突变体不能生长,而HsDHODH基因插入突变体能够生长。这表明HsDHODH是PoDHODH的替代品,喹诺菲林不能像在HsDHODH酶实验中那样抑制HsDHODH。比较人和真菌DHODHs的氨基酸序列表明,在泛素结合位点上的显著差异有助于喹诺菲林的物种选择性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Novel fungicide quinofumelin shows selectivity for fungal dihydroorotate dehydrogenase over the corresponding human enzyme.

The species selectivity of class 2 dihydroorotate dehydrogenase (DHODH), a target enzyme for quinofumelin, was examined. The Homo sapiens DHODH (HsDHODH) assay system was developed to compare the selectivity of quinofumelin for fungi with that for mammals. The IC50 values of quinofumelin for Pyricularia oryzae DHODH (PoDHODH) and HsDHODH were 2.8 nM and >100 µM, respectively. Quinofumelin was highly selective for fungal over human DHODH. Additionally, we constructed recombinant P. oryzae mutants where PoDHODH (PoPYR4) or HsDHODH was inserted into the PoPYR4 disruption mutant. At quinofumelin concentration of 0.01-1 ppm, the PoPYR4 insertion mutants could not grow, but the HsDHODH gene-insertion mutants thrived. This indicates that HsDHODH is a substitute for PoDHODH, and quinofumelin could not inhibit HsDHODH as in the HsDHODH enzyme assay. Comparing the amino acid sequences of human and fungal DHODHs indicates that the significant difference at the ubiquinone-binding site contributes to the species selectivity of quinofumelin.

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来源期刊
Journal of Pesticide Science
Journal of Pesticide Science 农林科学-昆虫学
CiteScore
4.30
自引率
4.20%
发文量
28
审稿时长
18-36 weeks
期刊介绍: The Journal of Pesticide Science publishes the results of original research regarding the chemistry and biochemistry of pesticides including bio-based materials. It also covers their metabolism, toxicology, environmental fate and formulation.
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