HPLC-MS/MS法发现ssaX阻断菌株中两个尿苷肽类新化合物  

Identification of two novel sansanmycin analogues from ssa X knockout strain by HPLC-MS/MS

作　　者：江志波[1] 侍媛媛[1] 任卫聪 范佳会 雷璇[1] 李星星[1] 王丽非[1] 解云英[1] 洪斌[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所/卫计委抗生素生物工程重点实验室,北京100050

出　　处：《中国医药生物技术》2018年第1期5-12,共8页Chinese Medicinal Biotechnology

基　　金：国家自然科学基金(81621064;81603006;81630089;81703398);中国医学科学院医学与健康科技创新工程(2016-I2M-3-012);"重大新药创制"国家科技重大专项(2017ZX09101003-006-011;2015ZX09102007-016)

摘　　要：目的对ssaX基因阻断菌株次级代谢产物中的sansanmycin类似物进行研究,发现新化合物。方法对Streptomyces sp.SS野生菌株及ssa X基因阻断株的发酵液分别进行固相萃取,收集60%甲醇水洗脱液进行HPLC-MS/MS分析。通过与文献报道的已知化合物数据相比较的方法,分析其中sansanmycin类化合物结构并利用MS/MS对其结构进行确证。结果从ssa X基因阻断株的发酵液中发现了8个sansanmycin类化合物,其中SS-MX-7和SS-MX-8为新结构化合物。SS-MX-7化学结构中假四肽肽链上的第一位和第四位氨基酸残基均为酪氨酸取代,而SS-MX-8的这两个位置均为苯丙氨酸。结论 ssa X基因阻断株产生的两个新sansanmycin类似物,进一步丰富了尿苷肽类化合物的结构多样性,同时也为利用HPLC-MS/MS方法在其他重组菌株中发现尿苷肽类新化合物奠定了基础。Objective To investigate the sansanmycin analogues produced by the ssa X knockout strain. Methods The fermentation supernatants of the wild type strain of Streptomyces sp. SS and ssa X knockout strain were extracted by the solid phase extraction cartridges, respectively. The 60%（V/V） Me OH/H2 O eluents were analyzed by HPLC-MS/MS. The chemical structures for sansanmycins were deduced by comparison of their MS/MS data to the known sansanmycins in the literatures. Results Eight sansanmycin analogues including two new structures were discovered from the ssa X knockout strain. Compound SS-MX-7 was found to bear two tyrosines（Tyr） substituted at the AA1 and AA4, respectively, while SS-MX-8 contained two phenylalanines（Phe） at the two positions. Conclusion Two new sansanmycin analogues were first identified from the fermentation extract of ssa X knockout strain, enriching the structural database of uridyl peptide antibiotics（UPAs）. The established HPLC-MS/MS method will facilitate the analysis of novel sansanmycin analogues from other recombinant strains.

关 键 词：尿苷肽类化合物 STREPTOMYCES sp.SS Sansanmycins HPLC-MS/MS 

分 类 号：R915[医药卫生—微生物与生化药学]