Siderophores hydroxamic acid units

Fig. 15. Citrate siderophores with two hydroxamic acid units...

Exochelins (322,323) are peptidic siderophores imm Mycobacterium spp. (see also below mycobactins). Exochelin MS (16) from M. smegmatis comprises (3-Ala and three W -OHOm units, which are linked by their atoms to acyl groups thus forming hydroxamic acids. 

In this chapter, we wiU concentrate mainly on hydroxamate-based siderophores. However, the most representative example of the catechol-based siderophore family is entero-bactin , a highly Cs-symmetric molecule based on a trilactone ring system derived from three L-serine amino acids. The serine amino groups are extended with three catecholic acid units. Enterobactin binds iron(III) in an octahedral coordination of preferred A-cis configuration (see Figure 1 in Section n.C). 

Growth factors (in concentrations of ca. 30 ng/mL) for Mycobacterium paratuberculosis (M. johnei), the microorganism responsible for Johne s disease in livestock. M. are iron chelators ( siderophores). 9 M. (M. A, F, H, M, N, P, R, S, and T) have been isolated from various non-pathogenic mycobacteria. They are used as taxonomic markers for mycobacteria. All M. form extremely stable hexacoordinate complexes in which the iron(III) is bound to two hydroxamic acid and one 2-(2-hydroxyphenyl)-2-oxazoline units. M. are stable towards heat and acids but unstable towards bases. On saponification the M. are cleaved to mycobactic acid and cobactin. M. show an apple green fluorescence under UV light. They are very soluble in chloroform... 

The fundamental structural unit of the ferrichromes, N -hydroxyomithine, is also present in rhodotorulic acid (and related compounds), the fusarinines (Ns-acyl-Ns-hydroxyornithine) and in neurosporin. The diversity of structure and biological activity of these siderophores results from the various substituents present in the peptide and acyl groups. The hydroxamate siderophores are better characterized from a structural viewpoint. X-ray diffraction data are available for the... 

The stabilities of Fe" complexes of hydroxamates are much lower than those of Fe " for the bis Fe" complex of acetohydroxamic acid = 3 x 10 ). It is thought, therefore, that the mechanism of release of iron from hydroxamate siderophores may occur via reduction of Fe " to the much more weakly bound Fe" state, as also proposed for the tris(catecholato) siderophores. Cyclic voltammetry has shown that the Fe" hydroxamate complexes undergo reversible or quasi-reversible one-electron reductions under suitable conditions. The observed formal potential E( is pH dependent, decreasing from —0.388 mV (ys. SCE) at pH 7 by 60 mV per pH unit, for the case of tris(acetohydroxamato)iron(III), consistent with progressive deprotonations of the coordinated ligand. Thus, deprotonation stabilizes the Fe " vs. the Fe state. ... 

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