Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, Department of Microbiology, College of Life Sciences, Nanjing Agricultural University, Jiangsu, Nanjing, People's Republic of China.
Appl Environ Microbiol. 2021 Jun 25;87(14):e0015621. doi: 10.1128/AEM.00156-21.
Nitrogen limitation has been widely reported to affect the growth and development of fungi, and the transcription factor GCN4 (general control nonderepressible 4) is involved in nitrogen restriction. Here, we found that nitrogen limitation highly induced the expression of GCN4 and promoted the synthesis of ganoderic acid (GA), an important secondary metabolite in Ganoderma lucidum. The activated GCN4 is involved in regulating GA biosynthesis. In addition, the accumulation of reactive oxygen species (ROS) also affects the synthesis of GA under nitrogen restrictions. The silencing of the gene led to further accumulation of ROS and increased the content of GA. Further studies found that GCN4 activated the transcription of antioxidant enzyme biosynthesis genes , , and (encoding glutathione reductase, glutathione -transferase, and catalase, respectively) through direct binding to the promoter of these genes to reduce the ROS accumulation. In conclusion, our study found that GCN4 directly interacts with the ROS signaling pathway to negatively regulate GA biosynthesis under nitrogen-limiting conditions. This provides an essential insight into the understanding of GCN4 transcriptional regulation of the ROS signaling pathway and enriches the knowledge of nitrogen regulation mechanisms in fungal secondary metabolism of Nitrogen has been widely reported to regulate secondary metabolism in fungi. Our study assessed the specific nitrogen regulatory mechanisms in Ganoderma lucidum. We found that GCN4 directly interacts with the ROS signaling pathway to negatively regulate GA biosynthesis under nitrogen-limiting conditions. Our research highlights a novel insight that GCN4, the nitrogen utilization regulator, participates in secondary metabolism through ROS signal regulation. In addition, this also provides a theoretical foundation for exploring the regulation of other physiological processes by GCN4 through ROS in fungi.
氮限制已被广泛报道会影响真菌的生长和发育，而转录因子 GCN4（一般控制不可抑制 4）参与氮限制。在这里，我们发现氮限制高度诱导 GCN4 的表达，并促进灵芝中重要的次生代谢产物灵芝酸（GA）的合成。激活的 GCN4 参与调节 GA 生物合成。此外，活性氧（ROS）的积累也会影响氮限制下 GA 的合成。基因的沉默导致 ROS 进一步积累并增加 GA 的含量。进一步的研究发现，GCN4 通过直接结合这些基因的启动子，激活抗氧化酶生物合成基因、和（分别编码谷胱甘肽还原酶、谷胱甘肽转移酶和过氧化氢酶）的转录，从而减少 ROS 的积累。总之，我们的研究发现，GCN4 在氮限制条件下通过直接与 ROS 信号通路相互作用，负调控 GA 生物合成。这为理解 GCN4 对 ROS 信号通路的转录调控提供了重要的见解，并丰富了氮在真菌次生代谢中调控机制的知识。已有研究报道氮调节真菌次生代谢，本研究评估了灵芝中特定的氮调控机制。我们发现，GCN4 在氮限制条件下通过直接与 ROS 信号通路相互作用，负调控 GA 生物合成。我们的研究强调了一个新的观点，即氮利用调节剂 GCN4 通过 ROS 信号调节参与次生代谢。此外，这也为探索 GCN4 通过 ROS 调节真菌中其他生理过程提供了理论基础。
