Zhao Huifang, Pang Na, Meng Xinyue, Qian Qiuyu, Han Qiqi, Han Qun, Zhang Xinlei, Fang Zemin, Liu Juanjuan
School of Life Sciences, Anhui University, Hefei, Anhui, China.
Anhui Key Laboratory of Biocatalysis and Modern Biomanufacturing, Hefei, Anhui, China.
Microbiol Spectr. 2025 Sep 2;13(9):e0048425. doi: 10.1128/spectrum.00484-25. Epub 2025 Jul 30.
Fungal-fungal interactions have attracted increasing attention due to alterations in physiological and developmental patterns and the upregulation of secondary metabolites. However, the molecular mechanisms underlying this phenomenon remain poorly understood. Previously, we reported that intracellular reactive oxygen species (ROS) function as signal molecules to induce defense responses in a basidiomycete fungus, , against a Mucoromycete fungus w5, concomitant with the upregulation of Skn7, a regulator participating in oxidative stress response. In this study, gene silencing and overexpression experiments demonstrated the involvement of Skn7 in mycelial growth and antioxidation in during cocultivation. According to the transcriptomic data, Skn7 was associated with the expression profiles of intracellular antioxidative enzymes, laccases, and secondary metabolite biosynthesis genes, including and . Chromatin immunoprecipitation followed by massively parallel sequencing analysis, along with electrophoretic mobility shift assay experiments, further confirmed the direct binding of Skn7 to these gene promoters. Another transcription factor, bHLH1, was identified to directly interact with Skn7 in regulating antioxidative defense mechanisms without influencing the expression of genes involved in secondary metabolite biosynthesis. Our work demonstrates Skn7 as a crucial transcription factor that orchestrates the regulatory network and targets downstream genes, thereby protecting against extracellular oxidative stress and elevated intracellular ROS levels during fungal-fungal interactions. Furthermore, we reveal the collaborative role of bHLH1 and Skn7 in fungal antagonism defense.IMPORTANCEFungal-fungal interactions are widespread and play a significant role in the function and stability of ecosystems. This study reveals the molecular mechanisms by which employs the transcription factors Skn7 and bHLH1 to coordinately regulate antioxidant defense mechanisms during its antagonistic interaction with w5. Skn7 not only directly regulates the expression of intracellular antioxidative enzymes and laccases but also regulates secondary metabolite biosynthesis genes. The two transcription factors collaborate to protect against oxidative stress. These findings deepen our understanding of signal transduction and defense mechanisms during fungal interactions, as well as provide new insights into the regulation of secondary metabolites in fungi.
由于生理和发育模式的改变以及次生代谢产物的上调，真菌与真菌之间的相互作用已引起越来越多的关注。然而，这一现象背后的分子机制仍知之甚少。此前，我们报道细胞内活性氧（ROS）作为信号分子，在担子菌真菌抵抗毛霉目真菌w5的过程中诱导防御反应，同时参与氧化应激反应的调节因子Skn7上调。在本研究中，基因沉默和过表达实验表明，Skn7在共培养期间参与了菌丝生长和抗氧化作用。根据转录组数据，Skn7与细胞内抗氧化酶、漆酶以及次生代谢产物生物合成基因（包括和）的表达谱相关。染色质免疫沉淀结合大规模平行测序分析以及电泳迁移率变动分析实验，进一步证实了Skn7与这些基因启动子的直接结合。另一个转录因子bHLH1被鉴定为在调节抗氧化防御机制中直接与Skn7相互作用，而不影响参与次生代谢产物生物合成的基因表达。我们的工作表明，Skn7是一个关键的转录因子，它协调调控网络并靶向下游基因，从而在真菌与真菌相互作用期间保护免受细胞外氧化应激和细胞内ROS水平升高的影响。此外，我们揭示了bHLH1和Skn7在真菌拮抗防御中的协同作用。重要性真菌与真菌之间的相互作用广泛存在，在生态系统的功能和稳定性中发挥着重要作用。本研究揭示了在与w5的拮抗相互作用过程中，利用转录因子Skn7和bHLH1协同调节抗氧化防御机制的分子机制。Skn7不仅直接调节细胞内抗氧化酶和漆酶的表达，还调节次生代谢产物生物合成基因。这两个转录因子协同作用以保护免受氧化应激。这些发现加深了我们对真菌相互作用期间信号转导和防御机制的理解，也为真菌次生代谢产物的调控提供了新的见解。
