xmniu@#ynu.edu.cn

解析小分子天然产物的合成和功能在生物适应环境变化过程中的作用机制研究

代表性论文（不超过10项）：

(1) Xiaoyu Yang^#, Yonghong Chen^#, Longlong Zhang^#, Jiangbo He^#, Qunfu Wu, Shuhong Li, Donglou Wang, Jianghui Gou, Zhuang Wu, Keqin Zhang, Shenghong Li*, Xuemei Niu*. Melanin precursors mediated adaption to temperature changes in fungus and animal via inhibition of lipid-mediated ferroptosis. Science China Life Science, 2023, doi: 10.1007/s11427-022-2265-6.

(2) Chen YH, Yang XY, Zhang LL, Wu QF, Li SH, Gou JH, He JB, Zhang KQ, LI SH, Niu XM. Tryptophan-centered metabolic alterations coincides with lipid-mediated fungal response to cold stress. Heliyon, 2023,9, e13066.

(3) Wu Z, Wu Q-F, Yuan W-L, Chen Y-H, Hu D, Deng D-Y, Zhang L-L, Niu X-M. Arthrocolins Synergizing with Fluconazole Inhibit FluconazoleResistant Candida albicans by Increasing Riboflflavin Metabolism and Causing Mitochondrial Dysfunction and Autophagy. Microbiology Spectrum, 2023, 10.1128/spectrum.04051-22.

(4) Jiao Zhou, Qun-Fu Wu, Shu-Hong Li, Jun-Xian Yan, Li Wu, Qian-Yi Cheng, Zhi-Qiang He, Xu-Tong Yue, Ke-Qin Zhang, Long-Long Zhang and Xue-Mei Niu.* The Multifaceted Gene 275 Embedded in the PKS-PTS Gene Cluster was Involved in the Regulation of Arthrobotrisin Biosynthesis, TCA Cycle, and Septa Formation of Nematode-Trapping Fungus Arthrobotrys oligospora. Journal of Fungi, 2022, 8, 1261. https://doi.org/10.3390/ jof8121261.

(5) Long-Long Zhang, Ya-Jun Liu, Yong-Hong Chen, Zhuang Wu, Bo-Ran Liu, Qian-Yi Cheng, Ke-Qin Zhang and Xue-Mei Niu*. Modulating Activity Evaluation of Gut Microbiota with Versatile Toluquinol. International Journal of Molecular Scicences 2022, 23, 10700. https://doi.org/10.3390/ijms231810700.

(6) Ya Wen, Qunfu Wu, Longlong Zhang, Jiangbo He, Yonghong Chen, Xiaoyu Yang, Keqin Zhang, Xuemei Niu* and Shenghong Li. Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment. Pathogens, 2022, 11, 784. https://doi.org/10.3390/pathogens11070784.

(7) Yonghong Chen, Longlong Zhang, Lijun Wang, Xutong Yue, Qunfu Wu, Yang Jiang, Keqin Zhang, Xuemei Niu*. Acetylation of sesquiterpenyl Epoxy-Cyclohexenoids regulates fungal growth, stress resistance, endocytosis, and pathogenicity of nematode-Trapping fungus Arthrobotrys oligospora via metabolism and transcription. Journal of Agricultural and food chemistry, 2022, 70:6145-6155.

(8) Zhiqiang He, Lijun Wang, Yujing Wang, Yonghong Chen, Ya Wen, Keqin Zhang, Xuemei Niu*. Polyketide synthase-terpenoid synthase hybrid pathway regulation of trap formation through ammonia metabolism controls soil colonization of predominant nematode-trapping fungus. Journal of Agricultural and Food Chemistry, 2021, 69: 4464-4479.

(9) Yonghong Chen, Xiao Liu, Rong Dai, Xia Ou, Zifei Xu, Keqin Zhang, Xuemei Niu*. Novel polyketide-terpenoid hybrid metabolites and increased fungal nematocidal ability by disruption of genes 277 and 279 in nematode-trapping fungus Arthrobotrys oligospora. Journal of Agricultural and Food Chemistry, 2020, 68: 7870-7879.

(10) Weiping Huang, Yuanjiang Du, Yun Yang, Jianing He, Qian Lei, Keqin Zhang, Xuemei Niu*. Development of Two CRISPR/Cas9 systems in Thermomyces dupontii and characterization of key gene functions in thermolide biosynthesis and fungal adaptation. Applied and Environmental Microbiology, 2020, 86: e01486-20.

小分子天然产物是创新药物的重要来源。新颖结构和重要生物活性的发现是天然产物研究领域中的关键创新要素。解析小分子天然产物的合成和功能在生物适应环境变化过程中的作用机制研究是发现和挖掘具有重要生物活性的天然药物的重要途径。发现一类在真菌中广泛存在的聚酮类小分子化合物在温度下降中大量积累，并导致黑色素产生。通过CRISPR/Cas9基因编辑，代谢组学和化学成分分离鉴定、转录组学，结合电子和透射显微镜观察，以及一系列生物测试分析和回补等综合实验，发现聚酮类小分子可以抑制低温诱导的脂肪和铁的大量积累，从而防治铁死亡（Ferroptosis）。进一步的动物小鼠和细胞低温测试表明，能产生黑色素的小鼠及其细胞显示出更强的抵抗温度下降的表型。更为重要的是，动物黑色素类前体小分子产物添加可以抑制由脂肪水平介导的细胞铁死亡。真菌和动物研究结果均表明黑色素前体小分子天然产物是一种新型的Ferroptosis防御系统，其特色是生物在低温下可以快速合成且低耗，并同时抑制脂肪生成。并提出了植物中抗低温的主要天然产物的结构类型为黄酮或者苯环小分子类化合物。揭示了一个有趣的小分子天然产物-脂肪-铁死亡-低温的关系，并为温度下降引起的感冒和为抗冷以及治疗药物的研发提供了一个新的视角。

发现一类具有荧光染料结构的含有四个芳香环取代的季碳的蒽类化合物Arthrocolins，可以显著抑制13株肿瘤细胞IC50 为0.4-5 μ M ，以及耐甲氧西林金黄色葡萄球菌和耐药性铜绿假单胞菌，协同氟康唑可以显著抑制耐氟康唑白色念珠菌的IC50 1.41-2.19μM。显著抑制感染肺癌小鼠的肿瘤以及小鼠的真菌感染，显著延长肿瘤小鼠的寿命。首次报道我国嗜热真菌中抗线虫活性天然产物,报道嗜热真菌化合物总数占全球该类真菌的42%。在国际化学，农业，微生物学和天然产物等领域等发表多篇高影响研究论文，包括J Am Chem Soc, Sci China Life Sci, Org Lett，J Agric Food Chem，Appl Environ Microb，J Nat Prod等国际一流学术期刊。