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Molecular fingerprints of conazoles via functional genomic profiling of Saccharomyces cerevisiae.
Toxicology in Vitro ( IF 3.2 ) Pub Date : 2020-09-09 , DOI: 10.1016/j.tiv.2020.104998
Miao Guan 1 , Pu Xia 2 , Mingming Tian 2 , Dong Chen 3 , Xiaowei Zhang 2
Affiliation  

Conazoles were designed to inhibit ergosterol biosynthesis. Conazoles have been widely used as agricultural fungicides and are frequently detected in the environment. Although conazoles have been reported to have adverse effects, such as potential carcinogenic effects, the underlying molecular mechanisms of toxicity remain unclear. Here, the molecular fingerprints of five conazoles (propiconazole (Pro), penconazole (Pen), tebuconazole (Teb), flusilazole (Flu) and epoxiconazole (Epo)) were assessed in Saccharomyces cerevisiae (yeast) via functional genome-wide knockout mutant profiling. A total of 169 (4.49%), 176 (4.67%), 198 (5.26%), 218 (5.79%) and 173 (4.59%) responsive genes were identified at three concentrations (IC50, IC20 and IC10) of Pro, Pen, Teb, Flu and Epo, respectively. The five conazoles tended to have similar gene mutant fingerprints and toxicity mechanisms. “Ribosome” (sce03010) and “cytoplasmic translation” (GO: 0002181) were the common KEGG pathway and GO biological process term by gene set enrichment analysis of the responsive genes, which suggested that conazoles influenced protein synthesis. Conazoles also affected fatty acids synthesis because “biosynthesis of unsaturated fatty acids” pathway was among the top-ranked KEGG pathways. Moreover, two genes, YGR037C (acyl-CoA-binding protein) and YCR034W (fatty acid elongase), were key fingerprints of conazoles because they played vital roles in conazole-induced toxicity. Overall, the fingerprints derived from the yeast functional genomic screening provide an alternative approach to elucidate the molecular mechanisms of environmental pollutant conazoles.



中文翻译:

通过酿酒酵母的功能基因组分析获得康唑类化合物的分子指纹。

康唑类药物旨在抑制麦角甾醇的生物合成。康唑类已被广泛用作农业杀菌剂,并且经常在环境中检测到。尽管据报道康唑类药物具有不良反应,例如潜在的致癌作用,但潜在的毒性分子机制仍不清楚。在这里,通过功能性全基因组敲除突变体分析在酿酒酵母(酵母)中评估了五种康唑(丙环唑 (Pro)、戊康唑 (Pen)、戊唑醇 (Teb)、氟硅唑 (Flu) 和氧唑菌 (Epo))的分子指纹图谱. 在三个浓度(IC 50、IC 20和 IC 10) 分别为 Pro、Pen、Teb、Flu 和 Epo。五种康唑类药物往往具有相似的基因突变指纹和毒性机制。“核糖体”(sce03010)和“细胞质翻译”(GO:0002181)是响应基因的基因集富集分析的常见KEGG途径和GO生物过程术语,这表明康唑影响蛋白质合成。康唑类也影响脂肪酸的合成,因为“不饱和脂肪酸的生物合成”途径是排名靠前的 KEGG 途径之一。此外,YGR037C(酰基辅酶A结合蛋白)和YCR034W(脂肪酸延长酶)这两个基因是康唑类药物的关键指纹,因为它们在康唑类药物引起的毒性中起着至关重要的作用。全面的,

更新日期:2020-09-16
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