Crochelins: Siderophores with an Unprecedented Iron‐Chelating Moiety from the Nitrogen‐Fixing Bacterium Azotobacter chroococcum

Microbes utilize siderophores to access essential iron resources. Over 500 siderophores are known, but they utilize a small set of common moieties to bind iron. Azotobacter chroococcum expresses iron-rich nitrogenases with which it reduces N2. Though an important agricultural inoculant, the structures of its iron-binding molecules remain unknown. Herein, we examine the 'chelome' of A. chroococcum using a small molecule discovery and bioinformatics approach. We find that it produces vibrioferrin and amphibactins as well as a novel family of siderophores, the crochelins. Detailed characterization shows that the most abundant member, crochelin A, binds iron in a hexadentate fashion using a new iron-chelating γ-amino acid. Insights into the biosynthesis of crochelins and the mechanism by which iron may be removed upon import of the holo-siderophore are presented. Our work expands the repertoire of iron-chelating moieties in microbial siderophores.