Siderophores are synthesized by microbes to facilitate iron acquisition required for growth. Catecholate, hydroxamate, and α-hydroxycarboxylate groups comprise well-established ligands coordinating Fe(III) in siderophores. Recently, a C-type diazeniumdiolate ligand in the newly identified amino acid graminine (Gra) was found in the siderophore gramibactin (Gbt) produced by Paraburkholderia graminis DSM 17151. The N−N bond in the diazeniumdiolate is a distinguishing feature of Gra, yet the origin and reactivity of this C-type diazeniumdiolate group has remained elusive until now. Here, we identify L-arginine as the direct precursor to L-Gra through the isotopic labeling of L-Arg, L-ornithine, and L-citrulline. Furthermore, these isotopic labeling studies establish that the N−N bond in Gra must be formed between the N δ and N ω of the guanidinium group in L-Arg. We also show the diazeniumdiolate groups in apo-Gbt are photoreactive, with loss of nitric oxide (NO) and H + from each D-Gra yielding E/Z oxime isomers in the photoproduct. With the loss of Gbt's ability to chelate Fe(III) upon exposure to UV light, our results hint at this siderophore playing a larger ecological role. Not only are NO and oximes important in plant biology for communication and defense, but so too are NO-releasing compounds and oximes attractive in medicinal applications. Articles pubs.acs.org/acschemicalbiology
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