丰肉结海绵相关链霉菌LS298活性代谢产物研究  

Bioactive metabolites produced by Streptomyces sp. LS298 isolated from the marine sponge Gelliodes carnosa

作　　者：崔美子[1] 巩婷[1] 朱平[1] 

机构地区：[1]北京协和医学院中国医学科学院药物研究所天然药物活性物质与功能国家重点实验室/卫生部天然药物生物合成重点实验室,100050

出　　处：《中国医药生物技术》2012年第6期418-425,共8页Chinese Medicinal Biotechnology

基　　金："十一五"国家科技重大专项"综合性新药研究开发技术大平台"(2009ZX09301-003-4-1);药物研究所基本科研业务费(2011CHX15)

摘　　要：目的对我国南海丰肉结海绵相关链霉菌LS298的活性代谢产物进行研究。方法采用硅胶柱、凝胶柱及HPLC等色谱方法对LS298发酵产物进行分离纯化;通过核磁共振、质谱等波谱分析手段对分离得到的化合物进行结构鉴定;以滤纸片扩散法及MTT法分别检测其抗菌和抗肿瘤活性。结果分离得到12个化合物。分别为尿嘧啶核苷、2'-脱氧尿嘧啶核苷、邻苯二甲酸正丁二酯、邻苯二甲酸二(2-乙基己)酯、3-甲酰胺-吲哚、环(脯氨酸-缬氨酸)、环(脯氨酸-苯丙氨酸)、环(脯氨酸-酪氨酸)、环(脯氨酸-亮氨酸)、meleagrin、5-hydroxyectoine和echinomycin。其中,3-甲酰胺-吲哚系首次从微生物中分离得到;meleagrin系首次从放线菌中分离得到。初步的药理研究表明,化合物echinomycin不仅具有较强的抗菌活性,亦具有很强的体外抗肿瘤活性。结论化合物echinomycin是链霉菌LS298的主要抗菌和抗肿瘤活性成分之一。Objective To study the active metabolites produced by the sponge-associated Streptomyces sp. LS298 isolated from the marine sponge Gelliodes carnosa collected from the South China Sea. Methods Chemical isolation and purification of the metabolites from the fermentation broth of the strain were conducted by means of silica gel column chromatography, Sephadex LH-20 column chromatography and high performance liquid chromatography （HPLC）, etc. Their structures were elucidated by MS, NMR and other spectroscopic analysis. The antibacterial activity and in vitro antitumor activity were detected by paper disc diffusion method and MTT method, respectively. Results Twelve metabolites were obtained and identified as uridine, 2＇-deoxyuridine, dibutylphthalate, bis （2-ethylhexyl） phthalate,indole-3-carboxamide, cyclo-（Pro-Val）, cyclo-（Pro-Phe）, cyclo-（Tyr-Pro）, cyclo-（Pro-Leu）, meleagrin, 5-hydroxyectoine, and echinomycin. Among these compounds, indole-3-carboxamide was isolated from the microorganisms for the first time, and meleagrin was first isolated from actinomycetes. Preliminary pharmacological studies showed that echinomycin exhibited a stronger antibacterial and cytotoxic activity. Conclusion The compound echinomycin is one of the main antibacterial and antitumor components of the Streptomyces sp. LS298.

关 键 词：链霉菌科 分离和提纯 抗生素类 抗 肿瘤 代谢产物 

分 类 号：R96[医药卫生—药理学]