Ferrichrome siderophores

The closely related structures show completely different microbial uptake characteristics. The 3D structures described above show distinct different orientation of the backbone amide (tangental in type 1 versus radial in type 2), which can be explained by the interactions that take place between the FhuA receptor and the ferrichrome siderophore -As mentioned, the second coordination sphere of natural ferrichrome in FhuA receptor is very sensitive to the distance and orientation between a proton donor and the proton acceptor, therefore the orientation of the amide groups in the biomimetic siderophore plays a crucial role in receptor recognition. 

Figure 2. Crystal and solution structure of the ferrichrome siderophores as determined by x-ray diffraction (11) and high resolution NMR (12). The ferrichrome peptides differ in the nature of the acyl substituent at the metal hydroxamate (R) and in the side chains of the three small, neutral, spacer amino acids (R1, R2, and R3). Ferrichrome M = Fe R = CHa R R2 = R3 = H (see also Figure 6 and Refs.

The X-ray crystallographic analysis of all ferrichrome siderophores yielded A-C-cis,cis configurations of the... 

Figure 3.2 Chemical structures of selected siderophores to demonstrate the four major structural classes and the different solutions of microorganisms to scavenge iron. See for comparison the conformations of the Fe3+-complexes of ferrichrome and albomycin shown in Figure 3.5.

Another factor that relates complex stability and siderophore architecture is the chelate effect. The chelate effect is represented by an increase in complex stability for a multidentate ligand when compared to complexes with homologous donor atoms of lower denticity. The effect can be observed when comparing the stability of complexes of mono-hydroxamate ligands to their tris-hydroxamate analogs, such as ferrichrome (6) or desferrioxamine B (4). However, the increase in stability alone is not sufficient to explain the preponderance of hexadentate siderophores over tetradentate or bidentate siderophores in nature, and the chelate effect is not observed to a great extent in some siderophore structures (10,22,50,51). 

Fig. 19. Plot of redox potentials (Ey2) as a function of pFe3+ values for a series of hexadentate, tetradentate, and bidentate hydroxamic acid siderophores and siderophore mimics. Data from Table V. Legend 1 — ferrioxamine E 2 — ferrioxamine B (4) 3 — H.aLjf4 (11) 4 — H >L 36 (12) 5 - coprogen 6 - ferricrocin 7 - ferrichrome (6) 8 - alcaligin 9 -rhodotorulic acid (3) 10 — NMAHA 11 — AHA 12 — Ly-AHA.

The FhuA receptor of E. coli transports the hydroxamate-type siderophore ferrichrome (see Figure 9), the structural similar antibiotic albomycin and the antibiotic rifamycin CGP 4832. Likewise, FepA is the receptor for the catechol-type siderophore enterobactin. As monomeric proteins, both receptors consist of a hollow, elliptical-shaped, channel-like 22-stranded, antiparallel (3-barrel, which is formed by the large C-terminal domain. A number of strands extend far beyond the lipid bilayer into the extracellular space. The strands are connected sequentially using short turns on the periplasmic side, and long loops on the extracellular side of the barrel. 

Figure 9. Structure of the siderophore ferrichrome (and derivatives) produced by certain fungal species...

As mentioned above, transport of siderophores across the cytoplasmic membrane is less specific than the translocation through the outer membrane. In E. coli three different outer membrane proteins (among them FepA the receptor for enterobactin produced by most E. coli strains) recognise siderophores of the catechol type (enterobactin and structurally related compounds), while only one ABC system is needed for the passage into the cytosol. Likewise, OM receptors FhuA, FhuE, and Iut are needed to transport a number of different ferric hydroxamates, whereas the FhuBCD proteins accept a variety of hydroxamate type ligands such as albomycin, ferrichrome, coprogen, aerobactin, shizokinen, rhodotorulic acid, and ferrioxamine B [165,171], For the vast majority of systems, the substrate specificity has not been elucidated, but it can be assumed that many siderophore ABC permeases might be able to transport several different but structurally related substrates. 

Figure 7.3 Structures of the siderophores enterobactin and ferrichrome. (From Andrews et al., 2003. Reproduced with permission from Blackwell Publishing Ltd.)...

In common with most prokaryotes many fungi have siderophore-dependent iron uptake systems. The ferrichrome-type siderophores are often employed, although other types of siderophore are also used. Indeed, even if, like the quintessential scavenger baker s yeast (S. cerevisiae), they produce no siderophores of their own, they nonetheless have several... 

Relationships between the structure of the siderophores and the iron transport were investigated for the fungus Neurospora crassa (160, 160a). Apparently two different receptors exist for ferrichromes and for coprogenes. For the recognition and the binding to the cell surface the iron configuration and the nature of the acyl chains is of importance. However, the transport system seems to be the same for both siderophore types dependent on the peptide part of the molecules. 

Jalal MAF, Hossain MB, van der Hehn D, Barnes CL (1988) Stmcture of Ferrichrome-type Siderophores with Dissimilar A -acyl Groups Asperchrome Bj, B2, B3, Dj, D2 and D3. Biol Metals 1 77... 

Jalal MAF, Mocharla R, van der Helm D (1984) Separation of Ferrichromes and Other Hydroxamate Siderophores of Fungal Origin by Reversed-phase Chromatography. J Chro-matogr 301 247... 

General mineral nutrition status improvement for the host plant has been studied frequently to understand the roles of endophytic fungi. Iron nutrition, however, has been studied only occasionally. P. fortinii strains obtained from Pinus sylvestris, Abies alba, Picea abies, and Carex curvula (the last a monocotyledonous plant) were found to produce the cyclic hexapeptide siderophores ferricrocin (73), ferrirubin (74) and ferrichrome C (75). The concentration and pattern of siderophore production was dependent on ferric ion concentration, pH of the medium, and the strain of endophyte. 

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