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基因组挖掘揭示了与抗菌和抗增殖活性相关的南极链霉菌的次生代谢产物。

Genome mining reveals secondary metabolites of Antarctic bacterium Streptomyces albidoflavus related to antimicrobial and antiproliferative activities.

机构信息

Division of Microbial Resources, Pluridisciplinary Center for Chemical, Biological and Agricultural Research, University of Campinas, Paulínia, SP, Brazil.

Graduate Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.

出版信息

Arch Microbiol. 2023 Oct 12;205(11):354. doi: 10.1007/s00203-023-03691-w.

Abstract

The urgent need for new antimicrobials arises from antimicrobial resistance. Actinobacteria, especially Streptomyces genus, are responsible for production of numerous clinical antibiotics and anticancer agents. Genome mining reveals the biosynthetic gene clusters (BGCs) related to secondary metabolites and the genetic potential of a strain to produce natural products. However, this potential may not be expressed under laboratory conditions. In the present study, the Antarctic bacterium was taxonomically affiliated as Streptomyces albidoflavus ANT_B131 (CBMAI 1855). The crude extracts showed antimicrobial activity against both fungi, Gram-positive and Gram-negative bacteria and antiproliferative activity against five human tumor cell lines. Whole-genome sequencing reveals a genome size of 6.96 Mb, and the genome mining identified 24 BGCs, representing 13.3% of the genome. The use of three culture media and three extraction methods reveals the expression and recovery of 20.8% of the BGCs. The natural products identified included compounds, such as surugamide A, surugamide D, desferrioxamine B + Al, desferrioxamine E, and ectoine. This study reveals the potential of S. albidoflavus ANT_B131 as a natural product producer. Yet, the diversity of culture media and extraction methods could enhance the BGCs expression and recovery of natural products, and could be a strategy to intensify the BGC expression of natural products.

摘要

对抗生素耐药性的迫切需求促使人们需要开发新的抗菌药物。放线菌,尤其是链霉菌属,负责生产许多临床抗生素和抗癌药物。基因组挖掘揭示了与次生代谢物相关的生物合成基因簇 (BGCs) 以及菌株产生天然产物的遗传潜力。然而,这种潜力在实验室条件下可能无法表达。在本研究中,南极细菌被分类为白色链霉菌 ANT_B131(CBMAI 1855)。粗提物显示出对真菌、革兰氏阳性和革兰氏阴性细菌的抗菌活性,以及对五种人肿瘤细胞系的抗增殖活性。全基因组测序揭示了基因组大小为 6.96 Mb,基因组挖掘鉴定了 24 个 BGCs,占基因组的 13.3%。使用三种培养基和三种提取方法揭示了 20.8% BGCs 的表达和回收。鉴定出的天然产物包括 surugamide A、surugamide D、去铁胺 B+Al、去铁胺 E 和 ectoine 等化合物。本研究揭示了白色链霉菌 ANT_B131 作为天然产物产生菌的潜力。然而,培养基和提取方法的多样性可以增强 BGCs 表达和天然产物的回收,这可能是一种强化 BGCs 表达天然产物的策略。

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