Siderophore Biosynthesis in Bacteria

The evolution of the biosynthetic routes to bacterial siderophores has been driven by the chemical demands imposed by the task of coordinating (and therefore making soluble) individual atoms of ferric iron (Fe3+). To serve as a chemically competent ligand to ferric iron, a functional group must possess a lone pair of electrons that has good electron donor properties. Bacteria have marshalled a diverse array of such functional groups for use in their siderophores, including phenolic hydroxyls, N-hydroxamates, the nitrogen constituents of five-member heterocyclic rings, and carboxylates. Each functional group defines a class of siderophores, and while some are the sole contingent of electron donors in a given siderophore, each of them has been found in combination with another. Siderophore scaffolds require flexibility and a certain amount of spatial extension, given that the molecule must wrap around an iron atom such that coordinating functional groups can be positioned at or near the optimal distances and angles. To make effective scaffolds, bacteria have chosen readily available materials that have the appropriate molecular handles to attach the required functional groups.