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探索短杆菌属中的生物合成基因簇:多样性和分布的比较基因组分析。

Exploring the biosynthetic gene clusters in Brevibacterium: a comparative genomic analysis of diversity and distribution.

机构信息

Centro de Biotecnología DAL, Universidad Técnica Federico Santa María, Valparaíso, Chile.

Department of Infectious Diseases, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

BMC Genomics. 2023 Oct 19;24(1):622. doi: 10.1186/s12864-023-09694-7.

DOI:10.1186/s12864-023-09694-7
PMID:37858045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10588199/
Abstract

Exploring Brevibacterium strains from various ecosystems may lead to the discovery of new antibiotic-producing strains. Brevibacterium sp. H-BE7, a strain isolated from marine sediments from Northern Patagonia, Chile, had its genome sequenced to study the biosynthetic potential to produce novel natural products within the Brevibacterium genus. The genome sequences of 98 Brevibacterium strains, including strain H-BE7, were selected for a genomic analysis. A phylogenomic cladogram was generated, which divided the Brevibacterium strains into four major clades. A total of 25 strains are potentially unique new species according to Average Nucleotide Identity (ANIb) values. These strains were isolated from various environments, emphasizing the importance of exploring diverse ecosystems to discover the full diversity of Brevibacterium. Pangenome analysis of Brevibacterium strains revealed that only 2.5% of gene clusters are included within the core genome, and most gene clusters occur either as singletons or as cloud genes present in less than ten strains. Brevibacterium strains from various phylogenomic clades exhibit diverse BGCs. Specific groups of BGCs show clade-specific distribution patterns, such as siderophore BGCs and carotenoid-related BGCs. A group of clade IV-A Brevibacterium strains possess a clade-specific Polyketide synthase (PKS) BGCs that connects with phenazine-related BGCs. Within the PKS BGC, five genes, including the biosynthetic PKS gene, participate in the mevalonate pathway and exhibit similarities with the phenazine A BGC. However, additional core biosynthetic phenazine genes were exclusively discovered in nine Brevibacterium strains, primarily isolated from cheese. Evaluating the antibacterial activity of strain H-BE7, it exhibited antimicrobial activity against Salmonella enterica and Listeria monocytogenes. Chemical dereplication identified bioactive compounds, such as 1-methoxyphenazine in the crude extracts of strain H-BE7, which could be responsible of the observed antibacterial activity. While strain H-BE7 lacks the core phenazine biosynthetic genes, it produces 1-methoxyphenazine, indicating the presence of an unknown biosynthetic pathway for this compound. This suggests the existence of alternative biosynthetic pathways or promiscuous enzymes within H-BE7's genome.

摘要

从各种生态系统中探索短杆菌菌株可能会发现新的抗生素产生菌株。短杆菌 sp. H-BE7 是从智利北部巴塔哥尼亚的海洋沉积物中分离出来的一株,对其基因组进行了测序,以研究在短杆菌属内产生新型天然产物的生物合成潜力。选择了 98 株短杆菌菌株的基因组序列进行基因组分析。生成了一个系统发育 cladogram,将短杆菌菌株分为四个主要分支。根据平均核苷酸同一性(ANIb)值,共有 25 株菌株可能是独特的新物种。这些菌株是从各种环境中分离出来的,这强调了探索不同生态系统以发现短杆菌属的全部多样性的重要性。短杆菌菌株的泛基因组分析表明,只有 2.5%的基因簇包含在核心基因组中,大多数基因簇要么作为单基因存在,要么作为少于 10 株存在的云基因存在。来自不同系统发育分支的短杆菌菌株表现出不同的 BGCs。特定的 BGC 组显示出分支特异性的分布模式,例如铁载体 BGC 和类胡萝卜素相关 BGC。一组 IV-A 短杆菌菌株拥有一个分支特异性的聚酮合酶(PKS) BGC,该 BGC 与吩嗪相关 BGC 相连。在 PKS BGC 中,包括生物合成 PKS 基因在内的五个基因参与甲羟戊酸途径,并与吩嗪 A BGC 具有相似性。然而,在九个主要从奶酪中分离出来的短杆菌菌株中,发现了额外的核心生物合成吩嗪基因。评估 H-BE7 菌株的抗菌活性,它对肠炎沙门氏菌和单核细胞增生李斯特菌表现出抗菌活性。化学去重复鉴定出生物活性化合物,如 H-BE7 粗提取物中的 1-甲氧基吩嗪,这可能是观察到的抗菌活性的原因。尽管 H-BE7 菌株缺乏核心吩嗪生物合成基因,但它能产生 1-甲氧基吩嗪,表明该化合物存在未知的生物合成途径。这表明 H-BE7 基因组中存在替代生物合成途径或混杂酶。

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