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首页> 外文期刊>Archives of microbiology >Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya
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Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya

机译:用含有来自牛链霉菌的硫霉素霉素基因簇的粘粒转化后,在白色链霉菌和轻链链霉菌中次级代谢产物的活化和沉默

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Activation and silencing of antibiotic production was achieved in Streptomyces albus J1074 and Streptomyces lividans TK21 after introduction of genes within the thienamycin cluster from S. cattleya. Dramatic phenotypic and metabolic changes, involving activation of multiple silent secondary metabolites and silencing of others normally produced, were found in recombinant strains harbouring the thienamycin cluster in comparison to the parental strains. In S. albus, ultra-performance liquid chromatography purification and NMR structural elucidation revealed the identity of four structurally related activated compounds: the antibiotics paulomycins A, B and the paulomenols A and B. Four volatile compounds whose biosynthesis was switched off were identified by gas chromatography-mass spectrometry analyses and databases comparison as pyrazines; including tetramethylpyrazine, a compound with important clinical applications to our knowledge never reported to be produced by Streptomyces. In addition, this work revealed the potential of S. albus to produce many others secondary metabolites normally obtained from plants, including compounds of medical relevance as dihydro-β-agarofuran and of interest in perfume industry as β-patchoulene, suggesting that it might be an alternative model for their industrial production. In S. lividans, actinorhodins production was strongly activated in the recombinant strains whereas undecylprodigiosins were significantly reduced. Activation of cryptic metabolites in Streptomyces species might represent an alternative approach for pharmaceutical drug discovery.
机译:在将基因从牛津链霉菌中引入噻吩霉素簇之后,在白色链霉菌J1074和青色链霉菌TK21中实现了抗生素产生的激活和沉默。与携带的亲代菌株相比,在含有噻菌霉素簇的重组菌株中发现了戏剧性的表型和代谢变化,涉及多种沉默次生代谢产物的激活和其他通常产生的沉默。在S. albus中,超高效液相色谱纯化和NMR结构解析揭示了四种与结构相关的活化化合物的身份:抗生素保乐霉素A,B和保乐美A和B。通过气体鉴定了四种生物合成被关闭的挥发性化合物。色谱-质谱分析和数据库比较为吡嗪;包括四甲基吡嗪,据我们所知从未在链霉菌中生产过这种化合物,具有重要的临床应用价值。此外,这项工作还揭示了白蜡梅有可能产生许多其他通常从植物中获得的次级代谢产物,包括医学上相关的化合物如二氢-β-agarofuran,在香水工业中令人关注的化合物如β-广atch香,表明这可能是工业生产的替代模型。在紫葡萄链球菌中,在重组菌株中强烈激活了放线菌丝蛋白的产生,而十一烷基谷胱甘肽酶显着降低。链霉菌属物种中隐性代谢物的激活可能代表了发现药物的另一种方法。

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