Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules.
Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules.
复制标题
比较代谢组学和结构特征照亮了依赖性小分子的结肠癌途径。
DOI：
10.1021/ja503450q
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发表时间：
2014-07-02
影响因子：
15
通讯作者：
Crawford, Jason M.
中科院分区：
文献类型：
--
作者：
Vizcaino, Maria I.;Engel, Philipp;Trautman, Eric;Crawford, Jason M.
在互利共生和致病性大肠杆菌中，已经鉴定出负责合成未知分子“colibactin”的基因簇。该途径赋予其生产者在人类肠道中的长期持久表型，用于治疗溃疡性结肠炎的益生菌活性，以及在宿主炎症条件下的致癌活性。迄今为止，尚未报道来自该途径的功能性小分子。在这里，我们实施了一个比较代谢组学和有针对性的结构网络分析方法，以确定一个目录的小分子依赖于大肠杆菌素途径从脑膜炎分离株E。coli IHE 3034和益生菌E. coliNissle1917年。基于结构表征和网络关系，提出了10种路径依赖小分子的结构。该网络将为该途径编码的各种其他小分子的结构和功能阐明提供路线图。从表征的小分子集，在体外细菌生长抑制和哺乳动物中枢神经系统受体拮抗剂活性。
The gene cluster responsible for synthesis of the unknown molecule “colibactin” has been identified in mutualistic and pathogenic Escherichia coli. The pathway endows its producer with a long-term persistence phenotype in the human bowel, a probiotic activity used in the treatment of ulcerative colitis, and a carcinogenic activity under host inflammatory conditions. To date, functional small molecules from this pathway have not been reported. Here we implemented a comparative metabolomics and targeted structural network analyses approach to identify a catalog of small molecules dependent on the colibactin pathway from the meningitis isolate E. coli IHE3034 and the probiotic E. coli Nissle 1917. The structures of 10 pathway-dependent small molecules are proposed based on structural characterizations and network relationships. The network will provide a roadmap for the structural and functional elucidation of a variety of other small molecules encoded by the pathway. From the characterized small molecule set, in vitro bacterial growth inhibitory and mammalian CNS receptor antagonist activities are presented.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Bonnet, Richard
DOI：
10.1073/pnas.1106030108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Schlessinger, Avner;Geier, Ethan;Sali, Andrej
通讯作者：
Sali, Andrej