Microbiology Department, College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, PR China; Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture and Rural Affairs, Nanjing 210095, Jiangsu, PR China.
Microbiol Res. 2022 May;258:126992. doi: 10.1016/j.micres.2022.126992. Epub 2022 Feb 16.
Nicotinamide adenine dinucleotide (NAD) is an important intracellular metabolite that is involved in different cel1lular processes. Glnmnat is the key enzyme that can affect intracellular NAD content. Here, we found that exogenous NAD treatment significantly increased ganoderic acid (GA) content in Ganoderma lucidum by 56.2%. Further experimental results showed that the acetylation level in Glnmnat-silenced strains significantly increased by about 35% and the transcript level of deacetylase Glsirt1 decreased by about 70%. Moreover, silencing Glnmnat led to a decrease in GA content, and this decrease could be rescued by the Glsirt1 activator. In addition, the acetylation of Glsirt1i-11 and Glsirt1i-21 was significantly increased by 28.8% and 41.0%. Furthermore, the decrease in GA content caused by silencing Glsirt1 could not be completely rescued by NAD treatment. Taken together, our study reveals that Glsirt1 is essential for the downstream regulation of GA biosynthesis by Glnmnat/NAD, emphasizes the importance of acetylation modification in the mechanism of GA biosynthesis, and provides ideas for other fungi to study secondary metabolic regulatory networks in epigenetics.
烟酰胺腺嘌呤二核苷酸（NAD）是一种重要的细胞内代谢物，参与多种细胞过程。Glnmnat 是一种关键酶，可以影响细胞内 NAD 含量。在这里，我们发现外源性 NAD 处理可使灵芝中的灵芝酸（GA）含量显著增加 56.2%。进一步的实验结果表明，沉默 Glnmnat 菌株中的乙酰化水平显著增加了约 35%，而去乙酰化酶 Glsirt1 的转录水平降低了约 70%。此外，沉默 Glnmnat 会导致 GA 含量降低，而这种降低可以被 Glsirt1 激活剂挽救。此外，Glsirt1i-11 和 Glsirt1i-21 的乙酰化水平分别显著增加了 28.8%和 41.0%。此外，沉默 Glsirt1 导致的 GA 含量降低不能完全被 NAD 处理挽救。总之，我们的研究揭示了 Glsirt1 是 Glnmnat/NAD 下游调控 GA 生物合成所必需的，强调了乙酰化修饰在 GA 生物合成机制中的重要性，并为其他真菌研究次生代谢调控网络的表观遗传学提供了思路。
