Coprogens acidity

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.

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. 

Fusarinines (19) produced by several fungal genera comprise the acyl unit (Z)-5-hydroxy-3-methyl-pent-2-enoic acid (anhydromevalonic acid) (Fig. 5, a) bound to W -hydroxy-L-omithine. They can be a linear monomer, dimer (fusarinine A) or trimer (fusarinine B) (the monomer can also be ( )-configured) 172). Fusarinine B is possibly identical with coprogen C 89). 

Coprogen is a hnear trihydroxamate produced by Penicillium species and Neurospora crassa and was first isolated and characterized by Hesseltine and coworkers . Coprogens are predominantly produced by fungi species and frequently several coprogens are produced by the same species. Coprogen is composed of Af -acyl-A -hydroxy-L-ornithine, anhydromevalonic acid and acetic acid. 

Coprogen is a linear trihydroxamate composed of three units of A -acyl-A -hydroxy-L-omithine, the acyl groups of which are represented by anhydromevalonic acid... 

After Fe + siderophores have docked at the binding pocket of the outer-membrane receptors of E. colt, translocation into the periplasmic space is mediated by the TonB complex. Once released into the periplasm, siderophores are rapidly bound by the specific periplasmic binding proteins FhuD (hydroxamate siderophores), FepB (enterobactin), and FecB (ferric dicitrate).FhuD, for example, exhibits a broad substrate specificity for a variety of hydroxamate siderophores including ferrichrome, coprogen, aerobactin, ferrioxamine B, shizokinen, rhodotorulic acid, and the antibiotic albomycin. The dissociation constants of FhuD with these siderophores range from 0.3 to 5.4 X-ray structures of FhuD... 

The first synthesis of a siderophore was the preparation of ferrioxamine B over 20 years ago in order to confirm the chemical structure of this natural product67). Synthesis of the other hydroxamate containing siderophores has as a central problem preparation of the constituent to-N-hydroxy amino acid in an optically pure form. The most important such subunit in hydroxamate siderophores is Ns-hydroxy ornithine. This is a chiral building block of the diketopiperazine-containing siderophores (rhodo-torulic acid 68), dimerum acid 69), coprogen 70) and coprogen B 69>), the cyclic hexa-peptides of the ferrichrome family27), the fusarinines 71 -73) and the antibiotic ferri-chrome derivatives albomycines Sl5 S2 and e 61-62). 

Fig. 31. Time dependent iron(III) uptake mediated by siderophores and synthetic analogs of rhodotorulic add (RA) n = 6 iso N,N -dihydroxy-N.N -diisopropyloc-tanediamide n = 8 me N,N -dihydroxy-N,N -methyldecanediamide n = 6 me N,N -dihydroxy-N.N -methyloctanedi-amide Dim dimerum acid Fox B ferrioxamine B Cop coprogen Fcr ferricrocin...

Table 2 UV/vis and CD spectra in solution of various geometrical and optical isomers of chromium (III) siderophores and of model compounds rhodoturulic acid (A), men (B), coprogen (C), enterobactin (D), catechol (E), and ferrioxamine B (F). UV/vis values are for Xmax (nm) and e (M cm ) CD values are for X ax (nm) and 0 (M cm )...

Diekmann, H. Metabolic Products of Microorganisms. 81. Occurrence and Structure of Coprogen and Dimerum Acid. Arch. Mikrobiol. 73, 65 (1970). 

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