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新型具有抗毒蕈碱活性的诺卡菌素衍生物,萜烯菌素 A-C,通过对诺卡氏菌 IFM 0406 的基因组挖掘发现。

New Nocobactin Derivatives with Antimuscarinic Activity, Terpenibactins A-C, Revealed by Genome Mining of Nocardia terpenica IFM 0406.

机构信息

Pharmaceutical Institute, Dept. of Pharmaceutical Biology, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.

German Center for Infection Research (DZIF) Partner site Tübingen, 72076, Tübingen, Germany.

出版信息

Chembiochem. 2020 Aug 3;21(15):2205-2213. doi: 10.1002/cbic.202000062. Epub 2020 Apr 2.

Abstract

We report a genomics-guided exploration of the metabolic potential of the brasilicardin producer strain Nocardia terpenica IFM 0406. Bioinformatics analysis of the whole genome sequence revealed the presence of a biosynthetic gene cluster presumably responsible for the generation of formerly unknown nocobactin derivatives. Mass spectrometry-assisted isolation led to the identification of three new siderophores, terpenibactins A (1), B (2) and C (3), which belong to the class of nocobactins. Their structures were elucidated by employing spectroscopic techniques. Compounds 1-3 demonstrated inhibitory activity towards the muscarinic M3 receptor, while exhibiting only a low cytotoxicity.

摘要

我们报告了一项基于基因组学的研究,探索了巴西卡林放线菌生产菌株诺卡氏菌 terpenica IFM 0406 的代谢潜力。对全基因组序列的生物信息学分析表明,存在一个生物合成基因簇,可能负责产生以前未知的 nocobactin 衍生物。质谱辅助分离导致了三种新的铁载体,terpenibactin A(1)、B(2)和 C(3)的鉴定,它们属于 nocobactin 类。通过光谱技术阐明了它们的结构。化合物 1-3 对毒蕈碱 M3 受体具有抑制活性,同时表现出低细胞毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f19/7497119/a2de7eff77ab/CBIC-21-2205-g001.jpg

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