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揭示链霉菌强效抗肿瘤和抗生素活性的代谢基因组学见解。来自瓦尔帕莱索湾的VB1。

Unveiling metabolo-genomic insights of potent antitumoral and antibiotic activity in Streptomyces sp. VB1 from Valparaíso Bay.

发表日期:2024
作者: Néstor Serna-Cardona, Leonardo Zamora-Leiva, Eduardo Sánchez-Carvajal, Fernanda P Claverías, Andrés Cumsille, Karla Alexa Pentón, Beatriz Vivanco, Alesia Tietze, Catherine Tessini, Beatriz Cámara
来源: Frontiers in Microbiology

摘要:

链霉菌属。 VB1 是一种从智利瓦尔帕莱索湾海洋沉积物中分离出来的放线菌,可合成抗菌和抗增殖化合物。本研究对 VB1 菌株进行了全面的代谢组学和比较基因组学分析。对粗提物进行 LC-HRMS 去重复和分子网络分析,鉴定出球霉素和柔红霉素等抗生素,以及 arylomycin 家族的已知和潜在新成员。这些化合物表现出针对一系列临床相关细菌和癌细胞系的活性。系统基因组分析强调了 VB1 菌株的独特性,表明它代表了一个新的分类单元。这种独特性得到了其生物合成新颖性指数 (BiNI) 和基因簇家族 (GCF) 的 BiG-SCAPE 分析的进一步支持。值得注意的是,与密切相关的菌株相比,VB1 有两个生物合成基因簇 (BGC) 是独特的:BGC #15,编码具有癌细胞生长抑制特性的潜在新型蒽环类化​​合物;BGC #28,具有非典型的结合了arylomycin、glolobomycin和siamycin BGC的配置。这个超簇首次被描述为由两个以上相邻且有功能的 BGC 组成,共同产生至少三种来自不同抗生素家族的抗菌化合物。这些发现突出了链霉菌属。 VB1 具有发现新生物活性分子的潜力,使其成为进一步研究的有希望的候选者。版权所有 © 2024 Serna-Cardona、Zamora-Leiva、Sánchez-Carvajal、Claverías、Cumsille、Pentón、Vivanco、Tietze、Tessini 和 Cámara。
Streptomyces sp. VB1, an actinomycete isolated from marine sediments in Valparaíso Bay, Chile, synthesizes antimicrobial and antiproliferative compounds. This study presents comprehensive metabolomics and comparative genomics analyses of strain VB1. LC-HRMS dereplication and Molecular Networking analysis of crude extracts identified antibiotics such as globomycin and daunorubicin, along with known and potentially novel members of the arylomycin family. These compounds exhibit activity against a range of clinically relevant bacterial and cancer cell lines. Phylogenomic analysis underscores the uniqueness of strain VB1, suggesting it represents a novel taxon. Such uniqueness is further supported by its Biosynthetic Novelty Index (BiNI) and BiG-SCAPE analysis of Gene Cluster Families (GCFs). Notably, two Biosynthetic Gene Clusters (BGCs) were found to be unique to VB1 compared to closely related strains: BGC #15, which encodes potentially novel anthracycline compounds with cancer cell growth inhibition properties, and BGC #28, which features a non-canonical configuration combining arylomycin, globomycin, and siamycin BGCs. This supercluster, the first described to consist of more than two adjacent and functional BGCs, co-produces at least three antimicrobial compounds from different antibiotic families. These findings highlight Streptomyces sp. VB1's potential for discovering new bioactive molecules, positioning it as a promising candidate for further research.Copyright © 2024 Serna-Cardona, Zamora-Leiva, Sánchez-Carvajal, Claverías, Cumsille, Pentón, Vivanco, Tietze, Tessini and Cámara.