Structure coprogens

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. 

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. 

Hossein MB, Jalal MAE, Benson BA, Barnes CL, van der Helm D (1987) Structure and Conformation of Two Coprogen-type Siderophores Neocoprogen I and Neocoprogen II. J Am Chem Soc 109 4948... 

Jalal MAF, van der Helm D (1989) Siderophores of Highly Phytopathogenic Alternaria longipes. Structures of Hydroxy coprogens. Biol Metals 2 11... 

The first of the coprogens (fungal sideramines ) was reported in 1973. Neocoprogen I (280) and neocoprogen II (281) are linear tris-hydroxamate siderophores whose chelating groups are derived from A -hydroxy-A -acylated ornithines. Neocoprogen I is the first structurally established example of a irons tris-hydroxamate siderophore. Subsequent studies have dealt with... 

TABLE 3. Natural coprogens and their structural variations... 

FIGURE 5. Schematic presentation of coprogen structure. The arrows indicate the relative directionality of the hydroxamate ligating groups in forming mer (trans) configurational isomers... 

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). 

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

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