Tang Fufang, Zhao Yuehan, Mao Zejing, Huang Yueyan, Hu Yifan, Liu Baixue, Huang Yanchun, Shao Yanchun
College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; Hubei International Scientific and Technological Cooperation Base of Traditional Fermented Foods, Huazhong Agricultural University, Wuhan 430070, China.
Int J Biol Macromol. 2025 May;308(Pt 4):142485. doi: 10.1016/j.ijbiomac.2025.142485. Epub 2025 Apr 1.
Monascus species can produce several secondary metabolites (SMs), which are regulated by a complex network. Histone deacetylase 1 (Hda1) has been demonstrated as a critical regulator of SMs and developmental processes; however, little is known about Hda1 in Monascus spp. (named MrHda1). In this study, strain ΔMrHda1 was generated for phenotypic assays. The results indicated that MrHda1 inactivation led to reduced conidia and ascospores but significantly increased pigment and citrinin production. Transcriptome data showed that MrHda1 deletion upregulated the expression of most genes in the glycolytic pathway as well as the gene clusters involved in pigment and citrinin biosynthesis. Western blotting (WB) and label-free acetylome data indicated that MrHda1 deletion significantly enhanced lysine acetylation modifications on the H3 subunit and enzymes involved in the citric acid cycle. Site-directed mutation demonstrated that the production of pigments and citrinin directly correlates with the acetylation level of histone H3 lysine 18 (H3K18). These findings provide new insights into the essential functions of MrHda1 and its regulation mechanisms on the SMs.
红曲霉菌种能够产生多种次级代谢产物（SMs），这些产物受一个复杂的网络调控。组蛋白去乙酰化酶1（Hda1）已被证明是次级代谢产物和发育过程的关键调节因子；然而，关于红曲霉菌种中的Hda1（命名为MrHda1）却知之甚少。在本研究中，构建了ΔMrHda1菌株用于表型分析。结果表明，MrHda1失活导致分生孢子和子囊孢子数量减少，但色素和桔霉素产量显著增加。转录组数据显示，MrHda1缺失上调了糖酵解途径中大多数基因以及参与色素和桔霉素生物合成的基因簇的表达。蛋白质免疫印迹（WB）和无标记乙酰化蛋白质组数据表明，MrHda1缺失显著增强了H3亚基和参与柠檬酸循环的酶上的赖氨酸乙酰化修饰。定点突变表明，色素和桔霉素的产生与组蛋白H3赖氨酸18（H3K18）的乙酰化水平直接相关。这些发现为MrHda1的基本功能及其对次级代谢产物的调控机制提供了新的见解。
