PDF(Pubmed)
Abstract：
Histone acetylation modification significantly affects secondary metabolism in filamentous fungi. However, how histone acetylation regulates secondary metabolite synthesis in the lovastatin (a lipid-lowering drug) producing Aspergillus terreus remains unknown because protein is involved and has been identified in this species. Here, the fungal-specific histone deacetylase gene, hstD, was characterized through functional genomics in two marine-derived A. terreus strains, Mj106 and RA2905. The results showed that the ablation of HstD resulted in reduced mycelium growth, less conidiation, and decreased lovastatin biosynthesis but significantly increased terrein biosynthesis. However, unlike its homologs in yeast, HstD was not required for fungal responses to DNA damage agents, indicating that HstD likely plays a novel role in the DNA damage repair process in A. terreus. Furthermore, the loss of HstD resulted in a significant upregulation of H3K56 and H3K27 acetylation when compared to the wild type, suggesting that epigenetic functions of HstD, as a deacetylase, target H3K27 and H3K56. Additionally, a set of no-histone targets with potential roles in fungal growth, conidiation, and secondary metabolism were identified for the first time using acetylated proteomic analysis. In conclusion, we provide a comprehensive analysis of HstD for its targets in histone or non-histone and its roles in fungal growth and development, DNA damage response, and secondary metabolism in A. terreus.
摘要：
组蛋白乙酰化修饰显著影响丝状真菌的次生代谢。然而,组蛋白乙酰化如何调节产生洛伐他汀(一种降脂药)土曲霉的次级代谢产物合成仍然未知,因为该物种中涉及蛋白质并已被鉴定.这里,真菌特异性组蛋白去乙酰化酶基因，hstD,通过功能基因组学对两种海洋来源的土曲霉菌株进行了表征，Mj106和RA2905。结果表明，HstD的消融导致菌丝生长减少，更少的分生孢子，洛伐他汀的生物合成减少，但土壤素的生物合成显着增加。然而,与酵母中的同源物不同，对DNA损伤剂的真菌反应不需要HstD，表明HstD可能在土曲霉的DNA损伤修复过程中起着新的作用。此外，与野生型相比，HstD的丢失导致H3K56和H3K27乙酰化的显着上调，表明HstD的表观遗传功能，作为脱乙酰酶，目标为H3K27和H3K56。此外,一组在真菌生长中具有潜在作用的无组蛋白靶标，分生孢子，首次使用乙酰化蛋白质组学分析鉴定了次级代谢。总之,我们全面分析了HstD在组蛋白或非组蛋白中的靶标及其在真菌生长和发育中的作用，DNA损伤反应,和土壤中的次生代谢。
