Siderophores degradation

The use of microbial siderophores by dicotyledonous plants appears to involve uptake of the entire metallated chelate (42-44), or an indirect process in which the siderophore undergoes degradation to release iron (45). As demonstrated in initial studies examining this question, there was concern that iron uptake from microbial siderophores may be an artifact of microbial iron uptake in which radiolabeled iron is accumulated by root-colonizing microorganisms (46). Consequently, evidence for direct uptake of iron from microbial siderophores has required the use of axenic plants. In experiments with cucumber, it was shown that the microbial siderophore ferrioxamine B could be used as an iron source at concentrations as low as 5 pM and that the siderophore itself entered the plant (42). 

The first of the haem uptake systems to be characterized at molecular level was that of Yersinia enterolitica, which closely resembles a typical siderophore uptake system (Stojiljkovic and Hantke, 1992, 1994), including a TonB-dependent outer membrane receptor for haem, a periplasmic binding protein, and a cytoplasmic membrane transport system. There also seems to be a protein that degrades haem and liberates haem iron within the cell. TonB-dependent outer membrane receptor proteins for haem have been cloned and sequenced from Shigella dysenteriae and E. coli (Mills and Payne, 1995 Torres and Payne, 1997), while in Vibrio cholera two genes are required for haem utilization, one an outer membrane receptor a second which may have a TonB-like function (Henderson and Payne, 1994). 

Thermobifida fusca, belonging to the Actinomycetales, produces three closely related siderophores, namely, the fuscachelins (92). Fuscachelin B starts with the sequence DHB - Arg-Gly-Gly-Ser, which is bound to the hydroxylated N -amino group of Om. Its N -amino group (the carboxyl group is free) is bound to the C-terminus of the sequence Gly-Gly-Arg-DHB (32). Fuscachelin A is considered to be the genuine metabolite, with B and C degradation products. 

The transport system of Bacillus subtilis accommodates the Fe " complexes of enterobactin (A-configured), enanfio-D-enterobactin and of corynebactin (bacilli-bactin) (both A). Since only A complexes can be bound to the receptor a configurational change from A to A is induced. Only the natural ferri-L-siderophores can be degraded enzymatically (399, 408). 

Barbeau K, Zhang G, Live DH, Butler A (2002) Petrobactin, a Photoreactive Siderophore Produced by the Oil-Degrading Marine Bacterium Marinobacter hydrocarhonoclasticus. J Am Chem Soc 124 378... 

Once the siderophore-iron complexes are inside the bacteria, the iron is released and utilized for vital cell functions. The iron-free hydroxamate siderophores are commonly re-excreted to bring in an additional iron load (Enterobactin is at least partially degraded by a cytoplasmic esterase This cycle is repeated until specific intracellular ferric uptake regulation proteins (Fur proteins) bind iron, and signal that the intracellular iron level is satisfactory, at -which point ne-w siderophore and siderophore-receptor biosynthesis are halted and the iron-uptake process stops. This intricate feedback mechanism allows a meticulous control over iron(III) uptake and accumulation against an unfavorable concentration gradient so as to maintain the intracellular iron(III) level within the required narrow window. Several excellent reviews concerning siderophore-iron transport mechanisms have been recently published i.3,i6, is,40,45,60-62 ... 

Those siderophores with low molecular weight, nonpeptidal structures are anticipated to be stable to proteolytic enzymatic degradation, and less likely to evoke an immune response. The antibiotic can be selected from commercial sources or from a large arsenal of potential antibiotics with low solubility that were overlooked, or never underwent extensive clinical investigations. 

Barbeau et al. [76] have also characterised the siderophore Petrobactin, produced by the oil-degrading bacterium Marinobacter hydrocarbonaoclasti-... 

Figure 10 A schematic drawing of the cell envelope of E. coli consisting of the cytoplasmic membrane, the periplasm, and the outer membrane. Various proteins are shown, sets of which represent specific siderophore-transport systems. Outer-membrane receptors (OMR) shown here are FepA (enterobactin), lutA (aerobactin), Fee A (Fe dicitrate), FhuA (ferrichrome), and FhuE (coprogen, Fe rhodotorulate, and ferrioxamine B). FoxA (ferrioxamine B), is not a receptor of E.coli, but of the closely related Salmonella. Not shown here are the receptors Fiu and Cir (Fe (DHBS) n indicates 3 possible linear degradation products of enterobactin) and FeO, a transport system for Fe . Details are discussed in Section 5.1...

Several natural products, for example siderophores, contain the N-hydroxy amide Y[CON(OH)] motif [138], Within a peptide backbone, this group increases the stability to enzyme degradation and induces characteristic conformational behavior [139]. In addition to the synthesis in solution of N-hydroxy amide-containing peptides (which is not trivial), a new solid-phase approach has recently been developed [140]. To explore the features of the N-hydroxy amide moiety using automated and combinatorial techniques, a method for the preparation of v /[CON(OH)] peptide ligands for MHC-I molecules has been elaborated [140], The strategy for the parallel preparation of these peptidomimetics on a solid support is illustrated in Scheme 7.9. The key step is the nucleophilic substitution reaction of resin-bound bromocarboxylic acids by O-benzylhydroxylamine, which requires several days. 

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