NRPS-Independent Siderophore Synthetases
Many bacteria produce siderophores that are used for iron acquitions. While many peptide siderophores are produced by NRPS enzymes, a number of hydroxamate siderophores are produced by a family of NRPS-Independent pathways and have been described as NIS compounds. These pathways often contain common decarboxylase, oxidase, and acyl-transferase enzymes that produce the hydroxamate. The hydroxamates are then combined with a carboxylate linker, often citric acid or alpha-keto glutarate.
The carboxylate is first activated through an adenylation reaction, similar to the chemistry seen in the ANL enzymes. In the second partial reaction, the NIS synthetase catalyzes amide formation. Kinetic studies with the NIS synthetase IucA has shown that all three substrates must bind to the enzyme active site prior to the reaction.
Structural Biology of NIS enzymes
Structures of multiple NIS enzymes have been determined, showing that the enzymes adopt an open conformation. Several conserved residues are implicated in ATP binding. On-going studies aim to understand the structural features that specify substrate preferences.