Li Run-Ya, Zhang Chen-Yu, Xiao Shaoxiang, Liu Xin-Yi, Li Ru-Xue, Li Jing, Li Hao, Liu Jun
Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, National Engineering Research Center of Rice and Byproduct Deep Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China.
Hunan Vocational College of Science and Technology, Changsha, 410004, Hunan, China.
Arch Microbiol. 2025 Mar 19;207(4):95. doi: 10.1007/s00203-025-04300-8.
Acetylation is an important modification type of histones, which is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, the histone acetylation level of Monascus was enhanced through the exogenous addition of the HDACs inhibitor vorinostat, and the regulation effects of histone acetylation on cell growth and secondary metabolism were evaluated. The results demonstrated that the augmentation of histone acetylation level could slightly facilitate sugar consumption, increase biomass weight, and significantly induce noticeable morphological alterations. Furthermore, in the presence of 80 μmol/L vorinostat concentration, there was a significant reduction observed in both extracellular and intracellular Monascus pigments, citrinin productions, with decreases of 35.46%, 63.90%, and 98.33% respectively. RT-qPCR results showed that adding vorinostat resulted in the up-regulation of HAT genes and down-regulation of HDAC genes. Additionally, transcriptome analysis revealed that glycolysis, tricarboxylic acid cycle, fatty acid metabolism, cell membrane anchor-protein related genes, and biosynthetic pathways involved in ergosterol and chitin synthesis were upregulated. Conversely, the electron transport chain and genetic clusters associated with Monascus pigments and citrinin synthesis were down-regulated. These findings underscore the pivotal role of histone acetylation in regulating the cell growth and secondary metabolism of M. purpureus and extend novel perspectives on the potential applications of clinical compounds derived from this process.
乙酰化是组蛋白的一种重要修饰类型，其受到组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）的动态调控。在本研究中，通过外源添加HDACs抑制剂伏立诺他提高了红曲霉菌丝体的组蛋白乙酰化水平，并评估了组蛋白乙酰化对细胞生长和次级代谢的调控作用。结果表明，组蛋白乙酰化水平的提高可略微促进糖消耗、增加生物量，并显著诱导明显的形态改变。此外，在80 μmol/L伏立诺他浓度下，细胞外和细胞内的红曲色素、桔霉素产量均显著降低，分别下降了35.46%、63.90%和98.33%。RT-qPCR结果显示，添加伏立诺他导致HAT基因上调和HDAC基因下调。此外，转录组分析表明，糖酵解、三羧酸循环、脂肪酸代谢、细胞膜锚定蛋白相关基因以及参与麦角固醇和几丁质合成的生物合成途径均上调。相反，与红曲色素和桔霉素合成相关的电子传递链和基因簇则下调。这些发现强调了组蛋白乙酰化在调节紫红红曲霉菌细胞生长和次级代谢中的关键作用，并为源自该过程的临床化合物的潜在应用拓展了新的视角。
