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