深海冷泉链霉菌OUCLQ20-1中大环内酰胺类化合物的发现  

Discovery of polycyclic tetramate macrolactams from deep-sea cold-seep derived Streptomyces sp.OUCLQ20-1

作　　者：岳亮光 赵一 单洁 邓发玉 李花月 YUE Liangguang;ZHAO Yi;SHAN Jie;DENG Fayu;LI Huayue(Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,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]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》2025年第1期57-64,共8页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(82073720,81991525);山东省自然科学基金项目(ZR2021ZD28)资助。

摘　　要：目的探究深海冷泉生态系统微生物产生丰富次级代谢产物潜力,挖掘冷泉链霉菌中具有生物活性的次级代谢产物。方法以抗多重耐药菌活性为导向,对冷泉链霉菌采用不同培养基发酵,确定使用AF/MS培养基进行大规模发酵,积累次级代谢产物。采用有机溶剂萃取、C18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、核磁共振数据分析以及文献比对,解析化合物结构,并进行抗菌活性测试。结果从冷泉来源链霉菌OUCLQ20-1中分离得到4个大环内酰胺类化合物ikarugamycin(1)、capsimycin D(2)、capsimycin G(3)和capsimycin C(4)。所有化合物对多重耐药菌Staphylococcus aureus CCARM 3090、Enterococcus faecium CCARM 5203与Enterococcus faecalis CCARM 5172展现出中等抑制活性。结论从冷泉链霉菌OUCLQ20-1中挖掘到一类大环内酰胺类化合物,具有潜在的药用价值,为冷泉生态系统的资源开发奠定基础。Objective To explore the potential of microorganisms in deep-sea cold-seep ecosystem to produce diverse secondary metabolites,and to explore the secondary metabolites with biological activity in coldseep derived Streptomyces.Methods Guided by the antibacterial activity against multidrug-resistant strains,the cold-seep derived Streptomyces sp.OUCLQ20-1 was fermented in different media,and AF/MS medium was used for large-scale fermentation to accumulate secondary metabolites.The fermentation products were separated by organic solvent extraction,Cis reversed-phase column chromatography and semi-preparative high-performance liquid chromatography.The structures of the compounds were identified by combination of mass spectrometry,nuclear magnetic resonance data analysis,and literature comparison,followed by the antibacterial activity evaluation.Results Four polycyclic tetramate macrolactams ikarugamycin(1),capsimycin D(2),capsimycin G(3)and capsimycin C(4)were isolated from the cold-seep derived Streptomyces sp.OUCLQ20-1.All compounds showed moderate inhibitory activity against multidrug-resistant bacteria Staphylococcus aureus CCARM 3090,Enterococcus faecium CCARM 5203 and Enterococcus faecalis CCARM 5172.Conclusion A class of polycyclic tetramate macrolactams with potential medicinal value were excavated from the cold-seep derived Streptomyces sp.OUCLQ20-1,which laid a foundation for the resource development of cold seep ecosystem.

关 键 词：冷泉链霉菌 次级代谢产物 多重耐药菌 抗菌活性 大环内酰胺 

分 类 号：R931.77[医药卫生—生药学]