Discovery of Sporachelins by Genome Mining of a Micromonospora Strain.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2024-11-19 DOI:10.1021/acs.jnatprod.4c00860

Xiaomeng Hao, Gang Wu, Hu Li, Xin Xiang, Jixiang Xu, Yuyu Liu, Zhongke Jiang, Shaowei Liu, Adeela Fatima, Maira Saleem, Feina Li, Zonggen Peng, Chenghang Sun

{"title":"Discovery of Sporachelins by Genome Mining of a Micromonospora Strain.","authors":"Xiaomeng Hao, Gang Wu, Hu Li, Xin Xiang, Jixiang Xu, Yuyu Liu, Zhongke Jiang, Shaowei Liu, Adeela Fatima, Maira Saleem, Feina Li, Zonggen Peng, Chenghang Sun","doi":"10.1021/acs.jnatprod.4c00860","DOIUrl":null,"url":null,"abstract":"Myxochelins are a group of catecholate siderophores encoded by mxc biosynthetic gene clusters (BGCs). They are mainly produced by myxobacteria and display a wide variety of bioactivities. Herein, we report a group of new myxochelins produced not by a myxobacterial strain but by an actinobacteria strain, Micromonospora sp. TMD166. They consisted of six new compounds, designated as sporachelins A (1), A1 (2), B (3), C (4), D (5), and E (6), and the known compound myxochelin A (7). The planar structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations were confirmed by Marfey's analysis and chemical synthesis. The six sporachelins are the first examples of acylated derivatives at the primary alcohol of myxochelin A. These molecules were found to inhibit human 5-lipoxygenase. In addition, 1-7 exhibited antifibrotic activity in the TGFβ1-induced human hepatic cell line LX-2 by suppressing fibrosis-related genes COL1A1, ACTA2, and TGFB1 expression. This is the first report of antifibrotic activity by myxochelins.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jnatprod.4c00860","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Myxochelins are a group of catecholate siderophores encoded by mxc biosynthetic gene clusters (BGCs). They are mainly produced by myxobacteria and display a wide variety of bioactivities. Herein, we report a group of new myxochelins produced not by a myxobacterial strain but by an actinobacteria strain, Micromonospora sp. TMD166. They consisted of six new compounds, designated as sporachelins A (1), A1 (2), B (3), C (4), D (5), and E (6), and the known compound myxochelin A (7). The planar structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations were confirmed by Marfey's analysis and chemical synthesis. The six sporachelins are the first examples of acylated derivatives at the primary alcohol of myxochelin A. These molecules were found to inhibit human 5-lipoxygenase. In addition, 1-7 exhibited antifibrotic activity in the TGFβ1-induced human hepatic cell line LX-2 by suppressing fibrosis-related genes COL1A1, ACTA2, and TGFB1 expression. This is the first report of antifibrotic activity by myxochelins.

查看原文本刊更多论文

通过小孢子菌株基因组挖掘发现孢子囊蛋白

肌螯素是由 mxc 生物合成基因簇（BGC）编码的一组儿茶胆酸苷元。它们主要由霉菌产生，具有多种生物活性。在此，我们报告了一组不是由粘菌菌株，而是由放线菌菌株--Micromonospora sp.它们包括六种新化合物，分别命名为 sporachelins A (1)、A1 (2)、B (3)、C (4)、D (5) 和 E (6)，以及已知化合物 myxochelin A (7)。平面结构是通过一维和二维核磁共振光谱数据的综合分析确定的，绝对构型则是通过马菲分析和化学合成确认的。这六种 sporachelins 是 myxochelin A 一级醇酰化衍生物的首个实例。此外，1-7 通过抑制纤维化相关基因 COL1A1、ACTA2 和 TGFB1 的表达，在 TGFβ1 诱导的人类肝细胞系 LX-2 中表现出抗纤维化活性。这是首次报道肌球蛋白具有抗纤维化活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.