Chiral linear hydroxamates as biomimetic analogues of ferrioxamine and coprogen and their use in probing siderophore-receptor specificity in bacteria and fungi

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Abstract
Linear hydroxamate derivatives, possessing chiral α-amino acid moieties, were synthesized and their iron transport activities were studied in bacteria and fungi. No growth-promoting activity could be detected in the Gram-positive hydroxamate-auxotrophAureobacterium flavescens JG9. However, Gram-negative enterobacteria, such asEscherichia coli, Pantoea agglomerans andHafnia alvei were able to utilize iron from these analogues. Uptake of55Fe-labeled analogues was inhibited by sodium azide, suggesting an active transport process. The receptors involved during uptake in enterobacteria were identified by using appropriate indicator organisms which are defective in the transport of either ferrioxamines (P. agglomerans FM13), coprogens (H. alvei), or both of these siderophore classes (E. coli fhuE). Our data suggest that the chiral hydroxamates are recognized by the ferrioxamine receptor (FoxA) and the coprogen receptor (FhuE) at a ratio which depends on the opticalν/δ isomer fraction and the nature of side chains. Transport was also observed in the fungusNeurospora crassa, known to take up coprogen rather than ferrioxamines, suggesting that in this fungus the synthetic analogues behave like coprogen.