海洋链霉菌Streptomyces sp.S063中聚酮类化合物alnumycins的发现  

Discovery of alnumycins from the marine-derived Streptomyces sp.S063

作　　者：岳亮光 黄会明 徐素玲 赵心清[3] 李花月 YUE Liangguang;HUANG Huiming;XU Suling;ZHAO Xinqing;LI Huayue(Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;School of Life Science,Liaocheng University,Liaocheng 252059,China;State Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiaotong University,Shanghai 200240,China;Laboratory for Marine Drugs and Bioproducts,Qingdao Marine Science and Technology Center,Qingdao 266237,China)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,医药学院,山东青岛266003 [2]聊城大学生命科学学院,山东聊城252059 [3]上海交通大学微生物代谢国家重点实验室生命科学技术学院,上海200240 [4]青岛海洋科技中心海洋药物与生物制品功能实验室,山东青岛266237

出　　处：《中国海洋药物》2024年第6期29-36,共8页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(82073720);青岛海洋科技中心“十四五”重大项目(2022QNLM030003-1)资助。

摘　　要：目的 挖掘海洋链霉菌中具有生物活性的次级代谢产物,为海洋药物的开发提供理论参考。方法 使用F2培养基对链霉菌进行大发酵,积累次级代谢产物。采用有机溶剂萃取、反相硅胶柱层析、半制备高效液相等分离手段对发酵产物进行分离纯化,通过质谱(MS)、核磁共振(NMR)数据分析以及文献比对,确定化合物结构,同时对所有化合物进行抗菌活性测试。运用生物信息学手段对Streptomyces sp. S063基因组中的生物合成基因簇进行预测和基因功能注释。结果 从海洋来源链霉菌Streptomyces sp. S063中分离得到4个聚酮类化合物alnumycin A(1)、alnumycin D(2)、alnumycin C(3)和K1115 A(4)。其中化合物1~3对多重耐药菌Staphylococcus aureus CCARM 3090展现出中等抑制活性。通过基因组生物信息学分析从Streptomyces sp. S063中定位到了alnumycin的生物合成基因簇(alm),并对1~4的生物合成途径进行了推测分析。结论 从海洋链霉菌Streptomyces sp. S063中挖掘到一类聚酮化合物alnumycins,具有潜在的药用价值,且其中所蕴含的其他化合物资源更有待深入挖掘。Objective Mining bioactive secondary metabolites from marine Streptomyces to provide theoretical reference for the development of marine drugs.Methods F2 medium was used for fermentation of Streptomyces to accumulate secondary metabolites.The crude extract was separated by ethyl acetate extraction,reverse phase silica gel chromatography and semi-preparative high performance liquid chromatography(HPLC).The structures of compounds were determined by MS analysis and NMR analysis as well as comparison with published literatures,and all compounds were tested for antibacterial activity.Bioinformatics methods were used to predict and annotate the biosynthetic gene clusters of Streptomyces sp.S063 genome.Results Three alnumycins compounds alnumycin A(1),alnumycin D(2)and alnumycin C(3),one anthraquinone compound K1115A(4)were isolated from marine Streptomyces sp.S063.Compounds 1-3 showed moderate inhibitory activities against Staphylococcus aureus CCARM 3090.The biosynthetic gene cluster of alnumycin(alm)was mapped from Streptomyces sp.S063 by bioinformatics analysis and the biosynthetic pathway of alnumycins in Streptomyces sp.So63 was proposed in combination with the literature.Conclusion A class of compounds with wide range of biological activities were excavated from marine Streptomyces sp.S063,which have potential medicinal value.At the same time,the biological value contained in marine Streptomyces sp.S063 needs to be further explored.

关 键 词：海洋链霉菌 次级代谢产物 抗菌活性 聚酮 alnumycins 

分 类 号：R931.77[医药卫生—生药学]