多重活性代谢组学从一种次源放线菌中分离大环内酯类。

IF 2.1 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Antibiotics Pub Date : 2024-12-06 DOI:10.1038/s41429-024-00792-6

Jordan T. Froese, Joseph A. Balsamo, Benjamin J. Reisman, Sierra M. Barone, Jonathan M. Irish, Brian O. Bachmann

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引用次数: 0

摘要

化学和生物刺激筛选在一个次生代放线菌被用来引发次生代谢。通过六个单细胞生物读数，使用多重活性谱法确定了生物活性天然产物的最佳生物合成。利用多重活性代谢组学方法，通过关联微滴度、分离良好的表型和提取的离子电流峰，对生物活性提取物进行分离，建立候选化合物。这指导了四种filipin多烯大环内酯的分离，包括一种新的代谢物filipin XV，一种烷基侧链羟基化的filipin链同源物，具有显著减弱的细胞毒性。用流式细胞术和荧光显微镜证实菲律宾特异性细胞毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Multiplexed activity metabolomics for isolation of filipin macrolides from a hypogean actinomycete

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Multiplexed activity metabolomics for isolation of filipin macrolides from a hypogean actinomycete

Chemical and biological stimulus screening in a hypogean actinomycete was used to elicit secondary metabolism. Optimal biosynthesis of bioactive natural products was identified using Multiplexed Activity Profiling for determining dose-dependent activity via six single-cell biological readouts. Bioactive extracts were fractioned to establish candidate compounds for isolation using Multiplexed Activity Metabolomics by correlating microtiter well-isolated phenotypes and extracted ion current peaks. This guided the isolation of four filipin polyene macrolides including a new metabolite filipin XV, an alkyl side-chain hydroxylated congener of the filipin chainin, with substantially attenuated cytotoxicity. Filipin-specific cytotoxicity was confirmed using flow cytometry and fluorescence microscopy.

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来源期刊

Journal of Antibiotics 医学-免疫学

CiteScore

6.60

自引率

3.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Antibiotics seeks to promote research on antibiotics and related types of biologically active substances and publishes Articles, Review Articles, Brief Communication, Correspondence and other specially commissioned reports. The Journal of Antibiotics accepts papers on biochemical, chemical, microbiological and pharmacological studies. However, studies regarding human therapy do not fall under the journal’s scope. Contributions regarding recently discovered antibiotics and biologically active microbial products are particularly encouraged. Topics of particular interest within the journal''s scope include, but are not limited to, those listed below: Discovery of new antibiotics and related types of biologically active substances Production, isolation, characterization, structural elucidation, chemical synthesis and derivatization, biological activities, mechanisms of action, and structure-activity relationships of antibiotics and related types of biologically active substances Biosynthesis, bioconversion, taxonomy and genetic studies on producing microorganisms, as well as improvement of production of antibiotics and related types of biologically active substances Novel physical, chemical, biochemical, microbiological or pharmacological methods for detection, assay, determination, structural elucidation and evaluation of antibiotics and related types of biologically active substances Newly found properties, mechanisms of action and resistance-development of antibiotics and related types of biologically active substances.