Siderophore biosynthetic pathway

Siderophore production refers to the biosynthetic pathway by which microorganisms, including many pathogenic bacteria and fungi, synthesize and secrete high-affinity iron-chelating molecules. These molecules, known as siderophores, are essential for microbial survival and virulence within the host environment, where they outcompete host proteins like transferrin and lactoferrin to scavenge iron. The biosynthesis typically involves complex multienzyme systems, such as non-ribosomal peptide synthetases (NRPS), polyketide synthases (PKS), and NRPS-independent siderophore (NIS) synthetases. Targeting these biosynthetic enzymes, particularly adenylation domains like MbtA in Mycobacterium tuberculosis or YbtE in Yersinia pestis, represents a promising strategy to induce iron starvation and reduce pathogenicity. Investigational inhibitors like salicyl-AMS and baulamycins aim to disrupt these processes to treat multidrug-resistant infections. Additionally, the siderophore transport system is leveraged by "Trojan horse" drugs, such as the approved antibiotic cefiderocol, which uses a siderophore-like moiety to achieve active transport into bacterial cells. Therapeutic challenges include the potential for pathogens to evolve resistance by utilizing alternative iron sources, such as heme or citrate, to bypass inhibited siderophore pathways.

Other names

Siderophore productionSiderophore biosynthesisSiderophore metabolic processIron acquisition pathway

Inhibition of siderophore biosynthesis enzymes, such as adenylation domains and non-ribosomal peptide synthetases, to prevent iron acquisition and attenuate pathogen virulence.