Ahmed Mohammed M A, Tripathi Siddarth K, Boudreau Paul D
Boudreau Lab, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United States.
Department of Pharmacognosy, Al-Azhar University, Cairo, Egypt.
Front Chem. 2023 Aug 24;11:1256962. doi: 10.3389/fchem.2023.1256962. eCollection 2023.
H16 is known to be a rich source of linear lipopeptide siderophores when grown under iron-depleted conditions; prior literature termed these compounds cupriachelins. These small molecules bear -hydroxyaspartate moieties that contribute to a photoreduction of iron when bound as ferric cupriachelin. Here, we present structural assignment of cupriachelins from B-4383 grown under iron limitation. The characterization of B-4383 cupriachelins is based on MS/MS fragmentation analysis, which was confirmed by 1D- and 2D-NMR for the most abundant analog (). The cupriachelin congeners distinguish these two strains with differences in the preferred lipid tail; however, our rigorous metabolomic investigation also revealed minor analogs with changes in the peptide core, hinting at a potential mechanism by which these siderophores may reduce biologically unavailable ferric iron (). Antifungal screening of the B-4383 supernatant extract and the isolated cupriachelin analog () revealed inhibitory activity against , with IC values of 16.6 and 3.2 μg/mL, respectively. This antifungal activity could be explained by the critical role of the iron acquisition pathway in the growth and pathogenesis of the fungal pathogen.
已知H16在缺铁条件下生长时是线性脂肽铁载体的丰富来源；先前的文献将这些化合物称为铜螯合菌素。这些小分子带有β-羟基天冬氨酸部分，当以铁铜螯合菌素形式结合时，有助于铁的光还原。在这里，我们展示了在铁限制条件下生长的B-4383产生的铜螯合菌素的结构鉴定。B-4383铜螯合菌素的表征基于MS/MS碎片分析，并通过1D和2D-NMR对最丰富的类似物进行了确认（）。铜螯合菌素同系物通过偏好的脂质尾部差异区分这两种菌株；然而，我们严格的代谢组学研究还发现了肽核心发生变化的次要类似物，这暗示了这些铁载体可能还原生物不可用的三价铁的潜在机制（）。对B-4383上清液提取物和分离出的铜螯合菌素类似物（）进行的抗真菌筛选显示对具有抑制活性，IC值分别为16.6和3.2μg/mL。这种抗真菌活性可以通过铁获取途径在真菌病原体生长和发病机制中的关键作用来解释。
