Emerimicins V-X, 15-Residue Peptaibols Discovered from an Acremonium sp. through Integrated Genomic and Chemical Approaches.
Emerimicins V-X, 15-Residue Peptaibols Discovered from an Acremonium sp. through Integrated Genomic and Chemical Approaches.
复制标题
DOI：
10.1021/acs.jnatprod.0c01186
复制
发表时间：
2021-02
影响因子：
5.1
通讯作者：
Guangwei Wu;B. Dentinger;J. Nielson;R. Peterson;Jaclyn M. Winter
中科院分区：
文献类型：
--
作者：
Guangwei Wu;B. Dentinger;J. Nielson;R. Peterson;Jaclyn M. Winter
从犹他大学收集的土壤样品中分离的tubakii Acremonium W. Gams进行发酵，分离并鉴定了六个新的线性五肽，emerimicins V-X（1-6）。含有15个残基的肽波士非常罕见，据报道只有22个。利用基因组挖掘和生物信息学分析，鉴定了含有单个16模块杂化聚酮-非核糖体肽合成酶的emerimicin 60 kbp eme生物合成簇。结合1D和2D NMR实验、LC-MS/MS数据和先进的Marfey's方法，对相应的15个腺苷酸化结构域进行了详细的生物信息学研究，从而可以对1-6中所有的蛋白源性和非蛋白源性氨基酸残基进行阐明和绝对构型。由于一些肽类化合物具有细胞毒活性，因此用斑马鱼胚胎毒性试验评估了六种emerimicin的毒性，结果表明emerimicin V(1)和VI(2)表现出最有效的活性。另外，在6种emerimicins中，1种对粪肠球菌、耐甲氧西林金黄色葡萄球菌和耐万古霉素粪肠球菌的MIC值分别为64、32和64 μg/mL，表现出适度的活性。
Fermentation of Acremonium tubakii W. Gams isolated from a soil sample collected from the University of Utah led to the isolation and characterization of six new linear pentadecapeptides, emerimicins V-X (1-6). Peptaibols containing 15-residues are quite rare, with only 22 reported. Genome mining and bioinformatic analysis were used to identify the emerimicin 60 kbp eme biosynthetic cluster harboring a single 16-module hybrid polyketide-nonribosomal peptide synthetase. A detailed bioinformatic investigation of the corresponding 15 adenylation domains, combined with 1D and 2D NMR experiments, LC-MS/MS data, and advanced Marfey's method, allowed for the elucidation and absolute configuration of all proteinogenic and nonproteinogenic amino acid residues in 1-6. As some peptaibols possess cytotoxic activity, a zebrafish embryotoxicity assay was used to evaluate the toxicity of the six emerimicins and showed that emerimicin V (1) and VI (2) exhibit the most potent activity. Additionally, out of the six emerimicins, 1 displayed modest activity against Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium with MIC values of 64, 32, and 64 μg/mL, respectively.