Siderophore electrochemistry: relation to intracellular iron release mechanism.

Abstract

Previous studies have shown that there is a major difference between the iron release mechanism of enterobactin, a catechol-based siderophore, and that of the hydroxamate-based siderophores such as ferrichrome. For ferric enterobactin there is an esterase that hydrolyzes the ligand during iron release. In contrast, iron is released by the hydroxamate-based siderophores and the ligands are reused in subsequent iron transport. It has been suggested that release of iron by hydroxamates occurs by reduction to the ferrous complex, a process that does not occur for ferric enterobactin. Cyclic vo tammograms of ferrichrome A and ferrioxamine B exhibit reversible one-electron waves with pH-independent formal potentials (Ef vs. the normal hydrogen electrode) -446 and -454 mV, respectively, within the range of physiological reductants. Ferric enterobactin also shows a reversible one-electron wave (at pH > 10) with Ef = -986 mV vs. the normal hydrogen electrode. From the pH dependence of this potential we estimate a reduction potential of -750 mV at pH 7. In sharp contrast to the value for the ferric hydroxamates, this value is well below the range of physiological reducing agents. The results demonstrate that the observed hydrolysis of enterobactin is a necessary prerequisite to in vivo release of iron from the siderophore via ferric ion reduction.

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin1

“…18,19 The reduction potentials of the salicylate analogs of ferric enterobactin (Table 4) are well within the range of biological reductants and much higher than those typically observed for the corresponding catecholate siderophores. Noteworthy, the reduction potentials observed for the hydroxamate siderophores ferrichrome A and ferrioxamine B are in the same range (Table 4).…”

“…Noteworthy, the reduction potentials observed for the hydroxamate siderophores ferrichrome A and ferrioxamine B are in the same range (Table 4). 18 The triserine trilactone stabilizes the ferrous over the ferric state compared with the TREN scaffold; 45 …”

“…16,17 This result implies the existence of a secondary pathway for intracellular iron release. While ferric enterobactin at neutral pH cannot release iron by reduction, 18,19 protonation of ferric enterobactin makes reduction much easier. 20 Furthermore, low pH binding of ferric enterobactin raises the question of whether a second type of structure might be recognized by proteins involved in ferric enterobactin metabolism.…”

Chrysobactin-dependent Iron Acquisition inErwinia chrysanthemi

“…For instance, this enzyme is required for the removal of iron from enterobactin analogs devoid of ester bonds (60,61). The redox potential of a ferric siderophore depends on the binding constant for iron and thus on the capacity of the molecule to be protonated at neutral pH (62). If the internal pH of E. chrysanthemi were slightly lower than that of E. coli, then iron would be easier to extract in E. chrysanthemi than in E. coli.…”

Mechanisms of Resistance in Escherichia coli to the Sideromycin Antibiotic No. 216: Isolation and Characterization of the Resistant Mutants

“…It has been reported that proteins in the outer membrane coded for by ton A and ton B genes are required for the uptake of sideromycins and Fe 3+-ferrichrome, and that the same proteins serve as receptors for phages TI, T5, and tj?80 and for colicin M (2,3,12,13,15,27,28). Acquisition of resistance to sideromycins is thought to be due to mutation of the genes coding for the ton A and ton B proteins in the outer membrane (6,9).…”