Kresna I Dewa M, Wuisan Zerlina G, Pohl Jean-Marie, Mettal Ute, Otoya Virginia Linares, Gand Martin, Marner Michael, Otoya Luis Linares, Böhringer Nils, Vilcinskas Andreas, Schäberle Till F
Institute for Insect Biotechnology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch for Bioresources, 35392 Giessen, Germany.
J Nat Prod. 2022 Apr 22;85(4):888-898. doi: 10.1021/acs.jnatprod.1c01018. Epub 2022 Mar 3.
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 sp. s120 genome sequence ( BGC). Comparative MS analysis of extracts from the native producer and a knockout mutant led to the identification of metabolites corresponding to the BGC. Furthermore, regulatory elements of the BGC were identified. By overexpression of an LmbU-like transcriptional activator, the production yield of and was increased, enabling isolation and structure elucidation of polyoxyperuin A seco acid () and polyoxyperuin A () using high-resolution mass spectrometry and NMR spectroscopy. Compound exhibited a low antibiotic effect against , while showed a strong Gram-positive antibiotic effect in a micro-broth-dilution assay.
氮杂丝氨酸菌素家族由几种具有不同药理生物活性的环状六肽缩酚酸肽组成，包括抗菌、抗肿瘤和诱导凋亡。在这项工作中，采用基因组挖掘方法，从sp. s120基因组序列中鉴定出一个编码氮杂丝氨酸菌素样化合物的生物合成基因簇（BGC）。对天然生产者和敲除突变体提取物的比较质谱分析导致鉴定出与BGC对应的代谢产物。此外，还鉴定了BGC的调控元件。通过过表达一种LmbU样转录激活因子，提高了和的产量，从而能够使用高分辨率质谱和核磁共振光谱对聚氧过菌素A裂酸（）和聚氧过菌素A（）进行分离和结构解析。化合物对表现出低抗生素效应，而在微量肉汤稀释试验中显示出强烈的革兰氏阳性抗生素效应。
