Derailment of the Biosynthesis via an Acid-Mediated Intramolecular Cyclo-rearrangement Leads to a Novel Cytochalasin Skeleton.

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2025-02-28 Epub Date: 2025-02-03 DOI:10.1021/acs.jnatprod.4c01296

Chenran Xu, Yao-Hui Shi, Wenjun Zhang, Jiafan Yang, Xiufeng Zhang, Shuo-Bin Chen, Yongxiang Song, Jing Xu, Yan Yan

{"title":"Derailment of the Biosynthesis via an Acid-Mediated Intramolecular Cyclo-rearrangement Leads to a Novel Cytochalasin Skeleton.","authors":"Chenran Xu, Yao-Hui Shi, Wenjun Zhang, Jiafan Yang, Xiufeng Zhang, Shuo-Bin Chen, Yongxiang Song, Jing Xu, Yan Yan","doi":"10.1021/acs.jnatprod.4c01296","DOIUrl":null,"url":null,"abstract":"Cytochalasins are notable for their structural diversity and broad range of biological activities. The gene cluster responsible for the biosynthesis of cytochalasins bearing diverse polycycles was identified in Phomopsis sp. DHS-48. Characterization of the cluster indicated that only the 5/6/11-tricycle can be biosynthetically produced. The chemical space of cytochalasins was expanded by acid-mediated intramolecular cyclo-rearrangement of the 5/6/11-tricycle, and three new cytochalasins, phomoparagins D-F (13, 17, and 18, respectively), with diversified polycycles were obtained, among which compound 13 featured an unprecedented 5/6/5/7/6-pentacycle. Their structures and absolute configurations were established by spectroscopic analysis (1D, 2D NMR), electronic circular dichroism calculations, and a single-crystal X-ray diffraction experiment. The compounds inhibited the growth of HeLa and RKO cell lines with IC50 values ranging from 0.8 to 47.3 μM. Cytoskeleton staining experiments and molecular docking models revealed that compound 13 showed cytotoxicity by targeting F-actin.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"477-484"},"PeriodicalIF":3.6000,"publicationDate":"2025-02-28","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.4c01296","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Cytochalasins are notable for their structural diversity and broad range of biological activities. The gene cluster responsible for the biosynthesis of cytochalasins bearing diverse polycycles was identified in Phomopsis sp. DHS-48. Characterization of the cluster indicated that only the 5/6/11-tricycle can be biosynthetically produced. The chemical space of cytochalasins was expanded by acid-mediated intramolecular cyclo-rearrangement of the 5/6/11-tricycle, and three new cytochalasins, phomoparagins D-F (13, 17, and 18, respectively), with diversified polycycles were obtained, among which compound 13 featured an unprecedented 5/6/5/7/6-pentacycle. Their structures and absolute configurations were established by spectroscopic analysis (1D, 2D NMR), electronic circular dichroism calculations, and a single-crystal X-ray diffraction experiment. The compounds inhibited the growth of HeLa and RKO cell lines with IC₅₀ values ranging from 0.8 to 47.3 μM. Cytoskeleton staining experiments and molecular docking models revealed that compound 13 showed cytotoxicity by targeting F-actin.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

通过酸介导的分子内环重排的生物合成脱轨导致一种新的细胞松弛素骨架。

细胞松弛素以其结构多样性和广泛的生物活性而闻名。在Phomopsis sp. DHS-48中鉴定出具有多种多环的细胞松弛素生物合成基因簇。聚类表征表明，只有5/6/11-三环可以生物合成。通过酸介导的5/6/11-三环的分子内环重排，扩大了细胞松弛素的化学空间，获得了3个新的细胞松弛素，phomoparagins D-F（分别为13、17和18），具有多种多环，其中化合物13具有前所未有的5/6/5/7/6-五环。通过光谱分析（1D, 2D NMR），电子圆二色性计算和单晶x射线衍射实验确定了它们的结构和绝对构型。化合物对HeLa和RKO细胞株的生长有抑制作用，IC50值在0.8 ~ 47.3 μM之间。细胞骨架染色实验和分子对接模型显示化合物13通过靶向F-actin表现出细胞毒性。

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分钟内获得全文去求助

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.