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Hetiamacin E 和 F,一种新型氨基糖苷类抗生素,来自 PJS 利用 MS/MS 为基础的分子网络技术。

Hetiamacin E and F, New Amicoumacin Antibiotics from PJS Using MS/MS-Based Molecular Networking.

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

出版信息

Molecules. 2020 Sep 27;25(19):4446. doi: 10.3390/molecules25194446.

Abstract

To combat escalating levels of antibiotic resistance, novel strategies are developed to address the everlasting demand for new antibiotics. This study aimed at investigating amicoumacin antibiotics from the desert-derived PJS by using the modern MS/MS-based molecular networking approach. Two new amicoumacins, namely hetiamacin E () and hetiamacin F (), were finally isolated. The planar structures were determined by analysis of extensive NMR spectroscopic and HR-ESI-MS data, and the absolute configurations were concluded by analysis of the CD spectrum. Hetiamacin E () showed strong antibacterial activities against methicillin-sensitive and resistant at 2-4 µg/mL, and methicillin-sensitive and resistant at 8-16 µg/mL. Hetiamacin F () exhibited moderate antibacterial activities against sp. at 32 µg/mL. Both compounds were inhibitors of protein biosynthesis demonstrated by a double fluorescent protein reporter system.

摘要

为了应对抗生素耐药性的不断升级,人们开发了新的策略来满足对新型抗生素的持久需求。本研究旨在利用现代基于 MS/MS 的分子网络方法,从沙漠来源的 PJS 中寻找amicoumacin 抗生素。最终分离出两种新型amicoumacin,分别为 hetiamacin E()和 hetiamacin F()。通过分析广泛的 NMR 光谱和 HR-ESI-MS 数据确定了它们的平面结构,通过分析 CD 光谱确定了它们的绝对构型。Hetiamacin E()对 2-4µg/mL 的甲氧西林敏感和耐药的 和 8-16µg/mL 的甲氧西林敏感和耐药的 表现出强烈的抗菌活性。Hetiamacin F()对 种属的 表现出中等的抗菌活性,浓度为 32µg/mL。这两种化合物都通过双荧光蛋白报告系统证明了它们是蛋白质生物合成的抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d13b/7583885/d74c5bcae2a1/molecules-25-04446-g001.jpg

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