Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete,Journal of Natural Products

当前位置： X-MOL 学术 › J. Nat. Prod. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete
Journal of Natural Products ( IF 3.3 ) Pub Date : 2022-03-03 , DOI: 10.1021/acs.jnatprod.1c01018
I Dewa M Kresna _{1,

2} , Zerlina G Wuisan _{1,

2,

3} , Jean-Marie Pohl _{1,

2} , Ute Mettal _{1,

2} , Virginia Linares Otoya ₄ , Martin Gand ₅ , Michael Marner ₂ , Luis Linares Otoya ₁ , Nils Böhringer _{1,

2,

3} , Andreas Vilcinskas _{1,

2} , Till F Schäberle _{1,

2,

3}

Affiliation

The azinothricin family comprises several cyclic hexadepsipeptides with diverse pharmacological bioactivities, including antimicrobial, antitumoral, and apoptosis induction. In this work, using a genome mining approach, a biosynthetic gene cluster encoding an azinothricin-like compound was identified from the Streptomyces sp. s120 genome sequence (pop BGC). Comparative MS analysis of extracts from the native producer and a knockout mutant led to the identification of metabolites corresponding to the pop BGC. Furthermore, regulatory elements of the BGC were identified. By overexpression of an LmbU-like transcriptional activator, the production yield of 1 and 2 was increased, enabling isolation and structure elucidation of polyoxyperuin A seco acid (1) and polyoxyperuin A (2) using high-resolution mass spectrometry and NMR spectroscopy. Compound 1 exhibited a low antibiotic effect against Micrococcus luteus, while 2 showed a strong Gram-positive antibiotic effect in a micro-broth-dilution assay.

中文翻译：

由海洋来源的链霉菌产生的 PKS-NRPS-杂合聚氧秘鲁蛋白的基因组挖掘指导发现和表征

阿齐丝菌素家族包含几种具有不同药理生物活性的环状六肽，包括抗微生物、抗肿瘤和诱导细胞凋亡。在这项工作中，使用基因组挖掘方法，从链霉菌中鉴定出编码阿齐丝菌素样化合物的生物合成基因簇。s120 基因组序列（pop BGC）。对来自本地生产者和敲除突变体的提取物进行比较 MS 分析，鉴定出对应于pop BGC 的代谢物。此外，还确定了 BGC 的监管要素。通过过表达 LmbU 样转录激活因子，产生1和2增加，从而能够使用高分辨率质谱和核磁共振光谱法分离和解析 polyoxyperuin A seco 酸 ( 1 ) 和 polyoxyperuin A ( 2 )。在微量肉汤稀释试验中，化合物1显示出对黄体微球菌的低抗生素作用，而化合物2显示出强的革兰氏阳性抗生素作用。

更新日期：2022-03-03

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南