Siderophore natural products as pharmaceutical agents

Siderophore natural products are characterized by an ability to tightly chelate metals. The origins of such compounds are often pathogenic microbes utilizing siderophores as virulence factors during host infection. The mechanism for siderophore formation typically involves the activity of nonribosomal peptide synthetases producing compounds across functional group classifications that include catecholate, phenolate, hydroxamate, and mixed categories. Though siderophore production has been a hallmark of pathogenicity, the evolutionarily-optimized binding abilities of siderophores suggest the possibility of re-directing the compounds towards alternative beneficial applications. In this mini-review, we will first describe siderophore formation origins before discussing alternative applications as pharmaceutical products. In so doing, we will cover examples and applications that include reducing metal overload, targeted antibiotic delivery, cancer treatment, vaccine development, and diagnostics. Included in this analysis will be a discussion on the native production hosts of siderophores and prospects for improvement in compound access through the adoption of heterologous biosynthesis.