Fungal NRPS-dependent siderophores: from function to prediction

Iron is an essential, yet often limiting element for the growth of many organisms. In response to iron limitation, fungi have developed siderophores that provide a high-affinity iron uptake system and safe intracellular storage and transport mechanisms to gain a competitive advantage. Here, we discuss the function of siderophores in relation to fungal iron uptake mechanisms and their importance for coexistence with host organisms. The chemical nature of the major groups of siderophores and their regulation is described along with the function and architecture of the large multi-domain enzymes responsible for siderophore synthesis, namely the non-ribosomal peptide synthetases (NRPSs). Finally, we present the most recent advances in our understanding of the structural biology of fungal NRPSs and discuss opportunities for the development of a fungal NRPS prediction server.