Integrated Omics-Based Discovery of Bioactive Halogenated Metabolites from the Deep-Sea Streptomyces sp. B188M101.

IF 5.4 2区医学 Q1 CHEMISTRY, MEDICINAL

Marine Drugs Pub Date : 2025-09-19 DOI:10.3390/md23090362

Emmanuel Tope Oluwabusola, Stephen A Jackson, Cristina Brunati, Stefanie Gackstatter, Hannah Vedder, Marianna Iorio, Gargee Chawande, Lekha Menon Margassery, Giang-Son Nguyen, David J Clarke, Rainer Ebel, Marcel Jaspars, Alan D W Dobson

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引用次数: 0

Abstract

Using the one-strain-many-compounds (OSMAC) culturing approach, metabolomic studies, and bioassay-guided purification, we have isolated and characterised three new chlorinated natural products, agelolines B-D (1-3), together with two known compounds, ageloline A (4) and gausemycin A (5), which have been identified by high-resolution mass spectrometry and 1D and 2D NMR analyses. The preliminary evaluation of three small-scale extracts (M400, R358 and SGG) against the fish pathogen, Aeromonas salmonicida subsp. achromogenes KELDUR265-87, showed that the R358 extract displayed significant activity. Furthermore, the natural products (1-5) were evaluated against the fish pathogen Aeromonas salmonicida and human pathogens (Stenotrophomonas maltophilia L2125, Staphylococcus aureus ATCC6538P, and S. pneumoniae L44) using a serial dilution assay. Compound 3 displayed activity against Staphylococcus aureus ATCC6538P, S. maltophilia L2125, and S. pneumoniae L44 with MIC values of 6, 32, and 64 µg/mL, respectively. Interestingly, only gausemycin A (5) exhibited considerable inhibition against A. salmonicida with an MIC value of 32 µg/mL, and the activity increased by two-fold when supplemented with 0.45 mM calcium salt, while 2 and 4 showed moderate inhibition against S. maltophilia L2125. The biosynthetic pathways of compounds 1-4 were proposed. This is the first report of specific inhibition of A. salmonicida by 5.

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深海链霉菌B188M101生物活性卤化代谢物的集成组学发现

利用单株多化合物（OSMAC）培养方法，代谢组学研究和生物测定指导纯化，我们分离并表征了三种新的氯化天然产物，凝胶碱B-D(1-3)，以及两种已知化合物，凝胶碱A(4)和高斯霉素A(5)，它们已被高分辨率质谱和1D和2D NMR分析鉴定。M400、R358和SGG三种小剂量提取物对鱼类致病菌沙门气单胞菌亚种的抑菌效果初步评价。结果表明，R358提取物具有显著的活性。此外，天然产物（1-5）对鱼类病原体沙门氏菌气单胞菌和人类病原体（嗜麦芽窄养单胞菌L2125，金黄色葡萄球菌ATCC6538P和肺炎链球菌L44）进行了一系列稀释试验。化合物3对金黄色葡萄球菌ATCC6538P、嗜麦芽葡萄球菌L2125和肺炎葡萄球菌L44的MIC值分别为6、32和64µg/mL。有趣的是，只有高斯霉素A(5)对沙门氏菌有明显的抑制作用，MIC值为32µg/mL，当添加0.45 mM钙盐时，活性增加了2倍，而2和4对嗜麦芽链球菌L2125有中等抑制作用。提出了化合物1 ~ 4的生物合成途径。这是5个菌株对沙门氏菌特异性抑制的首次报道。

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来源期刊

Marine Drugs 医学-医药化学

CiteScore

9.60

自引率

14.80%

发文量

671

审稿时长

1 months

期刊介绍： Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.