海参是海洋中重要的食物和药物资源，含有丰富的活性物质。海参共附生微生物非常丰富。为了从海参共附生微生物获得具有强生物活性的物质，对山东芝罘岛海域的仿刺参来源的共附生真菌Aspergillus terreus利用分子生物学手段进行了种属鉴定，并利用固体基进行培养，对其次级代谢产物进行了研究。通过薄层层析、柱层析、高效液相色谱对其化学成分进行了分离和纯化，综合核磁波谱、质谱对其进行结构鉴定。从该菌中获得dihydrogeodin (1)、Territrems A (2)、Territrems B (3)、2, 4-二羟基苯乙酮 (4)、questin (5)和emodin (6)六种物质。利用人口腔上皮癌细胞株（KB）和多药耐药性的细胞株（KBv200）对1, 5和6进行了细胞毒活性测试。本研究首次对化合物1进行了完整的谱图解析，并首次发现海洋环境来源的微生物可以代谢化合物dihydrogeodin (1)，以及具有强抑制乙酰胆碱酶活性Territrems (3)，而这些物质是海参本体不能够产生的，为开发具有预防和治疗帕金森病相关的功能食品提供了新来源。

Sea cucumber comprised of rich bioactive components is an important marine food and also used as a traditional medicine. There are various microbes associated with sea cucumber. In order to obtain effective bioactive compounds from Aspergillus terreus associated with Apostichopus japonicus from Zhifu Island, the fungus was cultivated on solid medium to investigate its secondary metabolites. Thin liquid chromatography (TLC), column chromatography and high performance liquid chromatography (HPLC) were used to separate secondary metabolites, and NMR, MS were used to identify their structures. As a result, dihydrogeodin (1), Territrems A (2), Territrems B (3), 1-(2, 4-dihydroxyphenyl)-ethanone (4), questin (5) and emodin (6) had been obtained and identified. KB and KBv200 were used to detect the cytotoxicity of 1, 5 and 6. It was the first time to determine intact Dihydrogeodin (1) by NMR and MS and it could be metabolized by marine fungus. In addition, it was firstly found that Territrem B (3) had the strongest inhibitory effects on acetylcholinesterase activities. Aspergillus terreus might be a new candidate for the development of functional food that can be used for preventing and treating Parkinson disease.

国家自然科学基金资助项目(81202452)；山东省优秀中青年科学奖励基金资助项目(BS2009HZ004)