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基于组学整合发现深海菌株B188M101的生物活性卤代代谢产物

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

作者信息

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

机构信息

Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3FX, UK.

School of Microbiology, University College Cork, College Road, T12 K8AF Cork, Ireland.

出版信息

Mar Drugs. 2025 Sep 19;23(9):362. doi: 10.3390/md23090362.

DOI:10.3390/md23090362
PMID:41003331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12471526/
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 (-), together with two known compounds, ageloline A () and gausemycin A (), 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, subsp. KELDUR265-87, showed that the R358 extract displayed significant activity. Furthermore, the natural products (-) were evaluated against the fish pathogen and human pathogens ( L2125, ATCC6538P, and L44) using a serial dilution assay. Compound displayed activity against ATCC6538P, L2125, and L44 with MIC values of 6, 32, and 64 µg/mL, respectively. Interestingly, only gausemycin A () exhibited considerable inhibition against with an MIC value of 32 µg/mL, and the activity increased by two-fold when supplemented with 0.45 mM calcium salt, while and showed moderate inhibition against L2125. The biosynthetic pathways of compounds - were proposed. This is the first report of specific inhibition of by .

摘要

采用单菌株多化合物（OSMAC）培养方法、代谢组学研究和生物测定导向纯化，我们分离并鉴定了三种新的氯化天然产物，agelolines B-D（-），以及两种已知化合物，ageloline A（）和高斯霉素A（），它们已通过高分辨率质谱以及一维和二维核磁共振分析得以鉴定。对三种小规模提取物（M400、R358和SGG）针对鱼类病原体 亚种KELDUR265 - 87的初步评估表明，R358提取物表现出显著活性。此外，使用系列稀释测定法对天然产物（-）针对鱼类病原体 和人类病原体（ L2125、 ATCC6538P和 L44）进行了评估。化合物 对 ATCC6538P、 L2125和 L44表现出活性，其最低抑菌浓度（MIC）值分别为6、32和64 µg/mL。有趣的是，只有高斯霉素A（）对 表现出相当大的抑制作用，MIC值为32 µg/mL，并且在补充0.45 mM钙盐时活性增加了两倍，而 和 对 L2125表现出中等抑制作用。提出了化合物 - 的生物合成途径。这是关于 对 的特异性抑制作用的首次报道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c491/12471526/cd3260335ada/marinedrugs-23-00362-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c491/12471526/cd3260335ada/marinedrugs-23-00362-g008.jpg

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