Kongsaya Tepakorn, Emthomya Nuttaporn, Ngamcharungchit Chananan, Aroonsri Aiyada, Uawisetwathana Umaporn, Pruksatrakul Thapanee, Euanorasetr Jirayut, Intra Bungonsiri
Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Mahidol University-Osaka University Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Appl Microbiol Biotechnol. 2025 Feb 25;109(1):50. doi: 10.1007/s00253-025-13427-z.
Cancer is a predominant contributor to global morbidity and mortality, affecting populations worldwide. Marine Micromonospora species have been identified as significant sources of anticancer compounds. This work aimed to perform a polyphasic approach of isolated strain and conduct comparative metabolomic and genomic analyses to identify compounds with anticancer activity. The study utilized a polyphasic approach on isolated strains for anticancer compound identification. Taxonomic analysis of strain 2MTK254 revealed unique pigment and fatty acid patterns, designating it as a novel Micromonospora carbonacea subsp. caeruleus. Its crude extract displayed significant anti-colorectal activity (66.03% inhibition). Molecular network analysis classified metabolites into eight classes, highlighting a polycyclic tetramate macrolactams (PTMs) compound (P1, CHNO) with 99.31% inhibitory activity against HCT-116 cell lines (IC at 0.125 µM). Genome analysis identified 32 biosynthetic gene clusters (BGCs), including unique PTMs BGCs (83% similarity) linked to the P1 compound. Thus, M. carbonacea subsp. caeruleus 2MTK254 holds promise as a source of novel PTMs with anti-colorectal cancer potential. KEY POINTS: • A novel strain of Micromonospora carbonacea subsp. caeruleus 2MTK254 was isolated in Thailand • A new polycyclic tetramate macrolactam (PTM) with anticancer activity was identified in 2MTK254 • The genome of 2MTK254 has unique secondary metabolite gene clusters.
癌症是全球发病和死亡的主要原因，影响着世界各地的人群。海洋小单孢菌属物种已被确定为抗癌化合物的重要来源。这项工作旨在对分离菌株采用多相方法，并进行比较代谢组学和基因组分析，以鉴定具有抗癌活性的化合物。该研究对分离菌株采用多相方法来鉴定抗癌化合物。对菌株2MTK254的分类分析揭示了独特的色素和脂肪酸模式，将其指定为一个新的天蓝小单孢菌碳亚种。其粗提物显示出显著的抗结直肠癌活性（抑制率为66.03%）。分子网络分析将代谢物分为八类，突出了一种对HCT-116细胞系具有99.31%抑制活性（IC为0.125µM）的多环四胺大环内酯（PTM）化合物（P1，CHNO）。基因组分析确定了32个生物合成基因簇（BGC），包括与P1化合物相关的独特PTM BGC（相似度83%）。因此，天蓝小单孢菌碳亚种2MTK254有望成为具有抗结直肠癌潜力的新型PTM的来源。要点：• 在泰国分离出一种新的天蓝小单孢菌碳亚种菌株2MTK254 • 在2MTK254中鉴定出一种具有抗癌活性的新的多环四胺大环内酯（PTM） • 2MTK254的基因组具有独特的次生代谢物基因簇。
