Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is now being appreciated, siderophores are among the strongest (highest affinity) Fe3+ binding agents known. Phytosiderophores are siderophores produced by plants.
Despite being one of the most abundant elements in the Earth's crust, iron is not readily bioavailable. In most aerobic environments, such as the soil or sea, iron exists in the ferric (Fe3+) state, which tends to form insoluble rust-like solids. To be effective, nutrients must not only be available, they must be soluble. Microbes release siderophores to scavenge iron from these mineral phases by formation of soluble Fe3+ complexes that can be taken up by active transport mechanisms. Many siderophores are nonribosomal peptides, although several are biosynthesised independently.
Siderophores are also important for some pathogenic bacteria for their acquisition of iron. In mammalian hosts, iron is tightly bound to proteins such as hemoglobin, transferrin, lactoferrin and ferritin. The strict homeostasis of iron leads to a free concentration of about 10−24 mol L−1, hence there are great evolutionary pressures put on pathogenic bacteria to obtain this metal. For example, the anthrax pathogen Bacillus anthracis releases two siderophores, bacillibactin and petrobactin, to scavenge ferric ion from iron containing proteins. While bacillibactin has been shown to bind to the immune system protein siderocalin, petrobactin is assumed to evade the immune system and has been shown to be important for virulence in mice.
Siderophores are amongst the strongest binders to Fe3+ known, with enterobactin being one of the strongest of these. Because of this property, they have attracted interest from medical science in metal chelation therapy, with the siderophore desferrioxamine B gaining widespread use in treatments for iron poisoning and thalassemia.
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