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对蓝色小单孢菌亚种产抗结直肠癌化合物的代谢组学和基因组学见解。

Metabolomic and genomic insights into Micromonospora carbonacea subsp. caeruleus for anti-colorectal compound.

作者信息

Kongsaya Tepakorn, Emthomya Nuttaporn, Ngamcharungchit Chananan, Aroonsri Aiyada, Uawisetwathana Umaporn, Pruksatrakul Thapanee, Euanorasetr Jirayut, Intra Bungonsiri

机构信息

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.

出版信息

Appl Microbiol Biotechnol. 2025 Feb 25;109(1):50. doi: 10.1007/s00253-025-13427-z.

Abstract

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.

摘要

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。

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