基于OSMAC与非靶向代谢组学的小链霉菌HCCB10043活性化合物挖掘  

Mining Active Compounds of Streptomyces parvus HCCB10043 based on OSMAC Strategy and Non-targeted Metabonomics

作　　者：张秋萍[1] 饶敏 魏维 Zhang Qiu-ping;Rao Min;Wei Wei(Zhejiang Medicine Co.,Ltd.Xinchang Pharmaceutical Factory,Xinchang 312500;Shanghai Laiyi Center for Biopharmaceuticals R&D,Shanghai 200240)

机构地区：[1]浙江医药股份有限公司新昌制药厂,新昌312500 [2]上海来益生物药物研究开发中心有限责任公司,上海200240

出　　处：《国外医药（抗生素分册）》2023年第2期102-107,共6页World Notes on Antibiotics

摘　　要：目的 基于OSMAC理念与非靶向代谢组学发现、鉴定小链霉菌产生的活性化合物。方法 通过改变培养基配方,结合抗菌活性检测与UPLC-HRMS技术,借助MS-MS数据解析、化合物库检索等手段分析并初步鉴定小链霉菌HCCB10043发酵产生的诺卡胺类化合物与Collismycin类化合物,并通过基因序列比对找到其生物合成基因簇。结果 在小链霉菌HCCB10043的M1培养基发酵提取物中发现了四个诺卡胺类物质(A-D),其中化合物A为新化合物;在M7培养基发酵提取物中发现了三个Collismycin类物质(E-G)。结论 诺卡胺类与Collismycin类化合物均是首次在小链霉菌中发现的具有抗菌活性的次级代谢产物。该结果进一步扩展了小链霉菌的代谢产物组,为提高其主要活性产物-重要抗生素达托霉素前体-A21978C化合物的产量提供理论基础;另一方面挖掘多样化的微生物天然活性产物,为新药研究提供化合物基础。Objective Discovery and identification of the active compounds from S.parvus based on OSMAC strategy and non-targeted metabonomics.Methods By changing the medium,combining the antibacterial activity detection and UPLC-HRMS technology,with the help of MS-MS data analysis and database search,the nocardamine compounds and collismycin compounds from metabolites of S.parvus HCCB10043 were analyzed and identified.Their biosynthetic gene clusters were found by gene sequence alignment.Results Four kinds of nocardamine and its derivatives(A-D),including compound A,a new one,were identified from the fermentation M1 extract of S.parvus.Three collismycin compounds(E-G)were identified from the fermentation M7 extract of S.parvus.Conclusion Seven antibacterial compounds were first discovered from S.parvus,which provided a theoretical basis for improving the yield of the main product A21978C-the precursor of daptomycin and enriched the quantity of active metabolites of Actinomyces to provide compound basis for new drug research.

关 键 词：小链霉菌 UPLC-MS 代谢组学 OSMAC 诺卡胺 collismycin 

分 类 号：R978[医药卫生—药品]