State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
Environ Microbiol. 2022 Nov;24(11):5596-5610. doi: 10.1111/1462-2920.16198. Epub 2022 Sep 16.
Aspergillus flavus is a ubiquitous saprotrophic soil-borne pathogenic fungus that causes crops contamination with the carcinogen aflatoxins. Although sirtuin E (SirE) is known to be a NAD-dependent histone deacetylase involved in global transcriptional regulation. Its biological functions in A. flavus are not fully understood. To explore the effects of SirE, we found that SirE was located in the nucleus and increased the level of H3K56 acetylation. The ΔsirE mutant had the most severe growth defect in the sirtuin family. The RNA-Seq revealed that sirE was crucial for secondary metabolism production as well as genetic information process and oxidation-reduction in A. flavus. Further analysis revealed that the ΔsirE mutant increased aflatoxin production. Both the sirE deletion and H3K56 mutants were highly sensitive to DNA damage and oxidative stresses, indicating that SirE was required for DNA damage and redox reaction by the H3K56 locus. Furthermore, the ΔsirE mutant displayed high sensitivity to osmotic stress and cell wall stress, but they may not be associated with the H3K56. Finally, the catalytic activity site N192 of SirE was required for regulating growth, deacetylase function and aflatoxin production. Together, SirE is essential for histone deacetylation and biological function in A. flavus.
黄曲霉是一种普遍存在的腐生土壤病原真菌，会导致农作物受到致癌物质黄曲霉毒素的污染。尽管已知 sirtuin E（SirE）是一种 NAD 依赖性组蛋白去乙酰化酶，参与全局转录调控。但其在黄曲霉中的生物学功能尚未完全阐明。为了研究 SirE 的作用，我们发现 SirE 位于细胞核内，并增加了 H3K56 乙酰化水平。在 sirtuin 家族中，ΔsirE 突变体的生长缺陷最为严重。RNA-Seq 表明 sirE 对次级代谢产物的产生以及遗传信息过程和氧化还原至关重要。进一步分析表明，ΔsirE 突变体增加了黄曲霉毒素的产生。sirE 缺失和 H3K56 突变体对 DNA 损伤和氧化应激均高度敏感，表明 SirE 是 DNA 损伤和 H3K56 位点氧化还原反应所必需的。此外，ΔsirE 突变体对渗透压和细胞壁应激高度敏感，但它们可能与 H3K56 无关。最后，SirE 的催化活性位点 N192 对于调节生长、去乙酰化酶功能和黄曲霉毒素的产生是必需的。总之，SirE 对黄曲霉的组蛋白去乙酰化和生物学功能至关重要。
