Coprogens

FhuE FhuD FhuB FhuC Coprogen Braun et ah, 1998... 

FhuE FhuE Outer membrane transport (coprogen) K-12 (Hantke, 1983)... 

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). 

For the designation of the acyl residues see Fig. 5 Coprogen C is possibly identical with fusarinine B (89)... 

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. 

Erythrochelin from Saccharopolyspora erythraea is a coprogen-type siderophore (Table 2) with Ac = i and Ac = o-Ser-o-A, A -diacetyl-A -hydroxy-Om 413). 

Anke H, Kinn J, Bergquist KE, Sterner O (1991) Production of Siderophores by Strains of the Genus Trichoderma. Isolation and Characterization of the New Lipophilic Coprogen Derivative, Pahnitoylcoprogen. Biol Metals 4 176... 

Diekmann H (1970) Stoffwechselprodukte von Mikroorganismen. 81. Mitteilung. Vorkom-men und Strukturen von Coprogen B und Dimerumsaure. Arch Microbiol 73 65... 

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... 

This enzyme [EC 1.3.3.3] (also referred to as copropor-phyrinogenase, coproporphyrinogen-III oxidase, and coprogen oxidase) catalyzes the reaction of coproporphyrinogen-111 with dioxygen to generate protoporphy-rinogen-lX and two carbon dioxide molecules. Iron ions are required as cofactors. 

Compounds 146-149 were examined for their iron-transport properties in a series of microorganisms including P. agglomerans, Hafnia and E. coli. All compounds were active however, they behaved as fenioxamine in H. alvi, as coprogen in E. coli and both as ferrioxamine and coprogen in P. agglomerans . In order to increase the differential... 

Based on the results described above, the chiral ferrioxamine analogs can be classified according to their uptake routes. The analogs that act both as ferrioxamine B and coprogen represent broad-range iron(III)-carriers, while others, such as the Glu derivatives, discriminating between different bacteria, correspond to narrow-range iron(III)-carriers. 

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. 

A selected number of coprogens (156-167), isolated and characterized, are listed in Table 3. 

While in the ferrioxamine biomimetics the aim was to reduce the conformational freedom by shortening the length of the spacers to prevent formation of mer (trans) isomers and favor instead the exclusive formation of the fac (cis) isomers, in preparing coprogen analogs the mer isomers are pursued. 

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