摘要
【背景】海洋微生物是复杂海洋生态环境中重要的生物资源之一。海洋微生物所产生的活性天然产物极为丰富,是药物或药物先导化合物的重要来源。【目的】探索海洋中海绵来源链霉菌Streptomycessp.S52-B的优势生长条件,挖掘其次级代谢产物,以期分离具有良好生物活性的天然产物。【方法】根据"One Strain Many Compounds"(OSMAC)策略,寻找利于Streptomyces sp.S52-B生长和次级代谢产物产生的优势培养基,结合质谱及特征性的紫外吸收谱图,选择培养基进行大量发酵。利用正相硅胶柱色谱、葡聚糖凝胶柱色谱和制备型高效液相色谱等进行分离纯化,并应用高分辨质谱和核磁共振光谱进行化合物结构解析。【结果】确定培养基A–D为海洋链霉菌S52-B的优势培养基,基于紫外吸收光谱与质谱分析,从培养基A的大量发酵物中分离鉴定3个具有吡咯并[4,3,2-de]喹啉核心结构的含氯化合物,属于氨酰胺类天然产物,其中Ammosalic acid为新结构化合物。【结论】已知含有吡咯并喹啉母核的氨酰胺类家族化合物具有优良的抗癌活性。本研究从海绵来源链霉菌S52-B中分离鉴定了3个氨酰胺类化合物,其中一个是新结构化合物,不仅丰富了此类化合物家族的结构类型,也为研究其生物合成途径中的未知机理奠定了基础,还有利于结合培养条件和基因组信息从这株海绵来源链霉菌中挖掘新结构的活性天然产物。
[Background]Marine microorganisms are one of the important biological resources in the complex marine ecological environment.The natural products produced by marine microorganisms are extremely abundant,which are the rich source of drug discovery.[Objective]Exploration of the optimal growth conditions of Streptomyces sp.S52-B,a sponge-derived Streptomyces,and excavation of its secondary metabolites in order to isolate new bioactive natural products.[Methods]According to the"One Strain Many Compounds"strategy,we optimized the cultural conditions of sponge-derived Streptomyces sp.S52-B which are suitable for mycelium growth as well as the production of secondary metabolites.Combining mass spectrometry and characteristic UV absorption spectra,one medium is selected for large scale fermentation.After purification by column chromatography and preparative high performance liquid chromatography(HPLC),the structure of the compounds were elucidated by high-resolution mass spectrometry(HR-MS)and nuclear magnetic resonance spectroscopy.[Results]The optimal medium of marine Streptomyces sp.S52-B was determined.Based on UV absorption spectroscopy and mass spectrometry analysis,three compounds with pyrrolo[4,3,2-de]quinolone were isolated and identified from a large scale fermentation using medium A.The chlorinated compounds with the pyrrolo[4,3,2-de]quinolone core structure belongs to the natural product of aminoamides,among which ammosalic acid is a new structure compound.[Conclusion]The aminosamide family compounds are known to have excellent anti-cancer activity.Three aminoamide compounds have been isolated and identified from the sponge-derived Streptomyces sp.S52-B,which not only enriches the structural types of such compounds,but also provides opportunity to combining culture conditions and genomic information to mine new structural active natural products from this strain.
作者
张馨元
王晓政
黄婷婷
林双君
李志勇
ZHANG Xinyuan;WANG Xiaozheng;HUANG Tingting;LIN Shuangjun;LI Zhiyong(State Key Laboratory of Microbial Metabolism,Joint International Laboratory on Metabolic&Developmental Sciences,School of Life Sciences&Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China)
出处
《微生物学通报》
CAS
CSCD
北大核心
2021年第7期2298-2306,共9页
Microbiology China
基金
国家重点研发计划(2019YFC0312501)
国家自然科学基金(21632007)
上海交通大学“新进青年教师启动计划”。
