Ma Zeyuan, Zhou Longjian, Yang Zhiyou, Liu Yayue, Zhang Yi
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Laboratory for Marine Biological Products, Guangdong Provincial Center for Modern Agricultural Scientific Innovation, Shenzhen Institute of Guangdong Ocean University, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524088, China.
J Fungi (Basel). 2025 Jul 23;11(8):546. doi: 10.3390/jof11080546.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with a pressing need for novel therapeutics. However, current medications only offer symptomatic relief, without tackling the underlying pathology. To explore the bioactive potential of marine-derived fungi, this study focused on C23-3, a strain isolated from the coral in Xuwen County, China, which showed a richer metabolite fingerprint among the three deposited strains. AntiSMASH analysis based on complete genome sequencing predicted 68 biosynthetic gene clusters (BGCs) with 7 BGCs synthesizing compounds reported to have anti-AD potential, including benzodiazepines, benzaldehydes, butenolides, and lovastatin. Liquid chromatography coupled with mass spectrometry (LC-MS)-based combinational metabolomic annotation verified most of the compounds predicted by BGCs with the acetylcholinesterase (AChE) inhibitor territrem B characterized from its fermentation extract. Subsequently, molecular docking showed that these compounds, especially aspulvione B1, possessed strong interactions with AD-related targets including AChE, cyclin-dependent kinase 5-p25 complex (CDK5/p25), glycogen synthase kinase-3β (GSK-3β), and monoamine oxidase-B (MAO-B). In conclusion, the genomic-metabolomic analyses and molecular docking indicated that C23-3 is a high-value source strain for anti-AD natural compounds.
阿尔茨海默病（AD）是一种普遍存在的神经退行性疾病，迫切需要新的治疗方法。然而，目前的药物仅能缓解症状，无法解决潜在的病理问题。为了探索海洋来源真菌的生物活性潜力，本研究聚焦于C23 - 3，这是一株从中国徐闻县珊瑚中分离出的菌株，在三个保藏菌株中其代谢物指纹图谱更为丰富。基于全基因组测序的AntiSMASH分析预测了68个生物合成基因簇（BGCs），其中7个BGCs合成的化合物据报道具有抗AD潜力，包括苯二氮䓬类、苯甲醛、丁烯内酯和洛伐他汀。基于液相色谱 - 质谱联用（LC - MS）的组合代谢组学注释验证了BGCs预测的大多数化合物，并从其发酵提取物中鉴定出乙酰胆碱酯酶（AChE）抑制剂特曲霉素B。随后，分子对接表明这些化合物，尤其是曲霉酮B1，与包括AChE、细胞周期蛋白依赖性激酶5 - p25复合物（CDK5/p25）、糖原合酶激酶 - 3β（GSK - 3β）和单胺氧化酶 - B（MAO - B）在内的AD相关靶点具有强烈相互作用。总之，基因组 - 代谢组学分析和分子对接表明C23 - 3是抗AD天然化合物的高价值来源菌株。
