{"title":"Analysis of Co-localized Biosynthetic Gene Clusters Identifies a Membrane-Permeabilizing Natural Product.","authors":"Xiaoyan Chen, Bo Li","doi":"10.1021/acs.jnatprod.3c01231","DOIUrl":null,"url":null,"abstract":"<p><p>Combination therapy is an effective strategy to combat antibiotic resistance. Multiple synergistic antimicrobial combinations are produced by enzymes encoded in biosynthetic gene clusters (BGCs) that co-localize on the bacterial genome. This phenomenon led to the hypothesis that mining co-localized BGCs will reveal new synergistic combinations of natural products. Here, we bioinformatically identified 38 pairs of co-localized BGCs, which we predict to produce natural products that are related to known compounds, including polycyclic tetramate macrolactams (PoTeMs). We further showed that ikarugamycin, a PoTeM, increases the membrane permeability of <i>Acinetobacter baumannii</i> and <i>Staphylococcus aureus</i>, which suggests that ikarugamycin might be an adjuvant that facilitates the entry of other natural products. Our work outlines a promising avenue to discover synergistic combinations of natural products by mining bacterial genomes.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-07-01","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.3c01231","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
Combination therapy is an effective strategy to combat antibiotic resistance. Multiple synergistic antimicrobial combinations are produced by enzymes encoded in biosynthetic gene clusters (BGCs) that co-localize on the bacterial genome. This phenomenon led to the hypothesis that mining co-localized BGCs will reveal new synergistic combinations of natural products. Here, we bioinformatically identified 38 pairs of co-localized BGCs, which we predict to produce natural products that are related to known compounds, including polycyclic tetramate macrolactams (PoTeMs). We further showed that ikarugamycin, a PoTeM, increases the membrane permeability of Acinetobacter baumannii and Staphylococcus aureus, which suggests that ikarugamycin might be an adjuvant that facilitates the entry of other natural products. Our work outlines a promising avenue to discover synergistic combinations of natural products by mining bacterial genomes.
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.
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