卡伍尔氏链霉菌NA4突变株ΔbafAI的次级代谢产物研究  

Secondary Metabolites of a Streptomyces cavourensis NA4 Mutant StrainΔbafAI

作　　者：张晓瑛 潘华奇[1] 张盈 石逸冰 鲍秀艳 胡江春[1] ZHANG Xiao-ying;PAN Hua-qi;ZHANG Ying;SHI Yi-bing;BAO Xiu-yan;HU Jiang-chun(Shenyang lnst.of Appl.Ecol.,Chinese Acad.of Sci.,Shenyang 110016;Chinese Acad.of Sci.,Beijing 100049;Shenyang Pharm.Uni.,Shenyang 110016)

机构地区：[1]中国科学院沈阳应用生态研究所,辽宁沈阳110016 [2]中国科学院大学,北京100049 [3]沈阳药科大学,辽宁沈阳110016

出　　处：《微生物学杂志》2019年第6期13-19,共7页Journal of Microbiology

基　　金：国家自然科学基金项目(41776178,41576136);辽宁省“兴辽英才计划”(XLYC1807268)。

摘　　要：链霉菌产生的次级代谢产物是农用和医药抗生素的重要来源。为了更深入挖掘卡伍尔氏链霉菌NA4潜在多样的次级代谢产物,对阻断NA4主产物bafilomycins的突变株ΔbafAI随机激活的代谢产物进行分离和鉴定。采用HP20固相萃取、硅胶柱色谱、凝胶柱色谱以及半制备HPLC等方法对ΔbafAI代谢产物进行分离纯化;使用NMR和MS确定化合物结构,并对单体化合物进行了生物活性测定。共分离鉴定6个化合物:环(L-异亮氨酸-L-脯氨酸)(1)、环(L-缬氨酸-L-脯氨酸)(2)、环(L-脯氨酸-L-亮氨酸)(3)、环(L-脯氨酸-L-苯丙氨酸)(4)、(2E,4E)-5-(3-羟苯基)-戊-2,4-二烯酰胺(5)和5′-脱氧-5′-甲硫肌苷(6)。6个化合物均是阻断NA4主产物后非特异激活的或产量显著提高的化合物,均为该菌中首次分离;化合物5和6是第二次从天然提取物中分离得到;化合物1和2显示出抗白色念珠菌活性,并首次报道了化合物5的抗氧化活性。进一步丰富了卡伍尔氏链霉菌NA4次级代谢产物研究,为激活沉默或低表达次级代谢产物合成基因簇提供了有益借鉴。Secondary metabolites of Streptomyces are important sources of agricultural and pharmaceutical antibiotics.In order to intensively explore the potential diversified secondary metabolites of Streptomyces cavourensis NA4,randomly activated metabolites of mutant strainΔbafAI which blocked bafilomycins,main product of NA4,were isolated and identified.HP20 solid phase extraction,silica gel column chromatography,and gel column chromatography and semi-prepared HPLC and other methods were used to isolate and purified the metabolites ofΔbafAI;the structures of the compounds were determined using NMR and MS,and the biological activity of the monomeric compounds was determined.A total of six compounds were isolated and identified:cyclo-(L-Ile-L-Pro)(1),cyclo-(L-Val-L-Pro)(2),cyclo-(L-Pro-L-Leu)(3),cyclo-(L-Pro-L-Phe)(4),(2E,4E)-5-(3-hydroxyphenyl)-penta-2,4-dienamide(5),5′-deoxy-5′-methylthioinosine(6).All of them were non-specifically activated compounds or significantly increase in yield after blocking the main products biosynthesis genes of NA4.All of the compounds were isolated firstly from NA4.Compounds 5 and 6 were obtained and isolated from natural extracts for the second time;compounds 1 and 2 showed inhibitory activities against Candida albicans,and antioxidant activity of compound 5 was firstly reported.This study further enriched the researches of the secondary metabolites of S.caverounsis NA4,and provided useful references for activating silent or low-expression secondary metabolite synthesis gene clusters.

关 键 词：海洋微生物 卡伍尔氏链霉菌(Streptomyces cavourensis) 次级代谢产物 基因敲除 生物活性 

分 类 号：Q939.9[生物学—微生物学]