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Glsirt1-mediated deacetylation of GlCAT regulates intracellular ROS levels, affecting ganoderic acid biosynthesis in Ganoderma lucidum
Free Radical Biology and Medicine ( IF 7.4 ) Pub Date : 2024-03-07 , DOI: 10.1016/j.freeradbiomed.2024.02.029
Jing Han , Lingshuai Wang , Xin Tang , Rui Liu , Liang Shi , Jing Zhu , Mingwen Zhao

Lysine acetylation is a reversible, dynamic protein modification regulated by lysine acetyltransferases and deacetylases. However, in Basidiomycetes, the extent of lysine acetylation of nonhistone proteins remains largely unknown. Recently, we identified the deacetylase sirt1 as a key regulator of the biosynthesis of ganoderic acid (GA), a key secondary metabolite of . To gain insight into the characteristics, extent, and biological function of -mediated lysine acetylation in , we aimed to identify additional sirt1 substrates via comparison of acetylomes between wild-type (WT) and -silenced mutants. A large amount of sirt1-dependent lysine acetylation occurs in according to the results of this omics analysis, involving energy metabolism, protein synthesis, the stress response and other pathways. Our results suggest that CAT is a direct target of sirt1 and that the deacetylation of CAT by sirt1 reduces catalase activity, thereby leading to the accumulation of intracellular reactive oxygen species (ROS) and positively regulating the biosynthesis of GA. Our findings provide evidence for the involvement of nonhistone lysine acetylation in the biological processes of and help elucidate the involvement of important ROS signaling molecules in regulating physiological and biochemical processes in this organism. In conclusion, this proteomic analysis reveals a striking breadth of cellular processes affected by lysine acetylation and provides new nodes of intervention in the biosynthesis of secondary metabolites in .

中文翻译:

Glsirt1介导的GlCAT去乙酰化调节细胞内ROS水平,影响灵芝中灵芝酸的生物合成

赖氨酸乙酰化是一种可逆的动态蛋白质修饰,受赖氨酸乙酰转移酶和脱乙酰酶调节。然而,在担子菌中,非组蛋白的赖氨酸乙酰化程度仍然很大程度上未知。最近,我们发现脱乙酰酶 Sirt1 是灵芝酸 (GA) 生物合成的关键调节因子,灵芝酸是灵芝的关键次级代谢产物。为了深入了解 β 介导的赖氨酸乙酰化的特征、程度和生物学功能,我们旨在通过比较野生型 (WT) 和 β 沉默突变体之间的乙酰化来鉴定其他 Sirt1 底物。根据组学分析结果,大量sirt1依赖性赖氨酸乙酰化发生,涉及能量代谢、蛋白质合成、应激反应等途径。我们的结果表明CAT是sirt1的直接靶标,sirt1对CAT的去乙酰化降低了过氧化氢酶活性,从而导致细胞内活性氧(ROS)的积累并正向调节GA的生物合成。我们的研究结果为非组蛋白赖氨酸乙酰化参与生物过程提供了证据,并有助于阐明重要的 ROS 信号分子参与调节该生物体的生理和生化过程。总之,这种蛋白质组分析揭示了受赖氨酸乙酰化影响的细胞过程的惊人广度,并为干预次生代谢物的生物合成提供了新的节点。
更新日期:2024-03-07
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