Desferrioxamines Research Articles

Convergent Synthesis of Macrocyclic and Linear Desferrioxamines

Polyhydroxamate desferrioxamines (DFO) are nontoxic siderophores endowed with high potential for development of therapeutic chelating agents. Herein, we report a modular and convergent strategy for diverse synthesis of macrocyclic and linear DFOs. The strategy employed orthogonally protected N‐hydroxy‐N‐succinylcadaverine building blocks, which allowed bidirectional extension of the DFO structure. The efficiency of the new strategy was demonstrated by the total synthesis of 44‐membered macrocyclic DFO‐T1, as well as four related DFO compounds in 11–13 linear steps and 2.1 %–10 % overall yields. Comparison of the iron binding affinity of the DFOs revealed DFO‐E as the best chelator.

Iron acquisition in the marine actinomycete genusSalinisporais controlled by the desferrioxamine family of siderophores

Many bacteria produce siderophores for sequestration of growth-essential iron. Analysis of the Salinispora genomes suggests that these marine actinomycetes support multiple hydroxamate- and phenolate-type siderophore pathways. We isolated and characterized desferrioxamines (DFOs) B and E from all three recognized Salinispora species and linked their biosyntheses in S. tropica CNB-440 and S. arenicola CNS-205 to the des locus through PCR-directed mutagenesis. Gene inactivation of the predicted iron-chelator biosynthetic loci sid2-4 did not abolish siderophore chemistry. Additionally, these pathways could not restore the native growth characteristics of the des mutants in iron-limited media, although differential iron-dependent regulation was observed for the yersiniabactin-like sid2 pathway. Consequently, this study indicates that DFOs are the primary siderophores in laboratory cultures of Salinispora.