Discovery of New Siderophores from a Marine <i>Streptomycetes</i> sp. via Combined Metabolomics and Analysis of Iron-Chelating Activity
Jianwei Chen, Yuqi Guo, Qihao Wu, Wei Wang, Jiangwei Pan, Ming‐Hong Chen, Hong Jiang, Qun-Jian Yin, Gaiyun Zhang, Bin Wei, Huawei Zhang, Hong Wang
Abstract
The marine-derived Streptomyces sp. FIMYZ-003 strain was found to produce novel siderophores with yields negatively correlated with the iron concentration in the medium. Mass spectrometry (MS)-based metabolomics coupled with metallophore assays identified two novel α-hydroxycarboxylate-type siderophores, fradiamines C and D ( 3 and 4 ), together with two related known siderophores, fradiamines A and B ( 1 and 2 ). Their chemical structures were elucidated by nuclear magnetic resonance (NMR) and MS experiments. The annotation of a putative fra biosynthetic gene cluster enabled us to propose the biosynthetic pathway of fradiamines A–D. Furthermore, the solution-phase iron-binding activity of fradiamines was evaluated using metabolomics, confirming them as general iron scavengers. Fradiamines A–D exhibited Fe(III) binding activity equivalent to that of deferoxamine B mesylate. Growth analysis of pathogenic microbes demonstrated that fradiamine C promoted the growth of Escherichia coli and Staphylococcus aureus, but fradiamines A, B, and D did not. The results indicate that fradiamine C may serve as a novel iron carrier applicable to antibiotic delivery strategies to treat and prevent foodborne pathogens.