Bacterial siderophores assist pathogens in iron acquisition inside their ho
sts. They are often essential for achieving a successful infection, and the
ir biosynthesis represents an attractive antibiotic target. Recently, sever
al siderophore biosynthetic loci have been identified, and in vitro studies
have advanced our knowledge of the biosynthesis of aryl-capped peptide and
peptide-polyketide siderophores from Mycobacterium spp., Pseudomonas spp.,
Yersinia spp. and other bacteria. These studies also provided insights int
o the assembly of related siderophores and many secondary metabolites of me
dical relevance. Assembly of aryl-capped peptide and peptide-polyketide sid
erophores involves non-ribosomal peptide synthetase, polyketide synthase an
d non-ribosomal-peptide polyketide hybrid subunits. Analysis of these subun
its suggests that their domains and modules are functionally and structural
ly independent. It appears that nature has selected a set of functional dom
ains and modules that can be rearranged in different order and combinations
to biosynthesize different products. Although much remains to be learned a
bout modular synthetases and synthases, it is already possible to conceive
strategies to engineer these enzymes to generate novel products.