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通过代谢组学和基因组学方法从海洋来源的链霉菌中发现新的埃博霉素类似物

Discovery of New Everninomicin Analogs from a Marine-Derived sp. by Metabolomics and Genomics Approaches.

作者信息

Lee Tae Hyun, Brittin Nathan J, Alas Imraan, Roberts Christopher D, Chanana Shaurya, Braun Doug R, Ericksen Spencer S, Guo Song, Rajski Scott R, Bugni Tim S

机构信息

Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705, USA.

Small Molecule Screening Facility, UW Carbone Cancer Center, Madison, WI 53792, USA.

出版信息

Mar Drugs. 2025 Jul 31;23(8):316. doi: 10.3390/md23080316.

Abstract

During the course of genome mining initiatives, we identified a marine-derived , assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal component analysis () revealed that WMMD956 displayed an extreme degree of metabolomic and genomic novelty. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and Global Natural Product Social molecular networking platform (GNPS) analysis of WMMD956 resulted in the identification of several analogs of the previously known everninomicin. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, and the use of MS/MS data. The isolated metabolites, -, were evaluated for their antibacterial activity against methicillin-resistant (MRSA).

摘要

在基因组挖掘计划过程中,我们鉴定出一株源自海洋的菌株,在此命名为WMMD956;WMMD956的基因组似乎包含许多与埃维霉素相关的特征,埃维霉素是著名的抗微生物原霉素。此外,基于液相色谱-质谱联用的层次聚类分析和主成分分析表明,WMMD956表现出极高程度的代谢组学和基因组新颖性。对WMMD956进行高分辨率串联质谱(HRMS/MS)的去重复分析以及全球天然产物社会分子网络平台(GNPS)分析,鉴定出了几种先前已知的埃维霉素类似物。通过高分辨电喷雾电离质谱、一维和二维核磁共振实验以及质谱/质谱数据的使用,明确确认了化学结构。对分离得到的代谢产物-进行了针对耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌活性评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9029/12387530/12ff32b5b2dd/marinedrugs-23-00316-g001.jpg

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