Iron transport ferrioxamines

The po.ssible role of a chelate reductase for iron uptake from microbial siderophores has been examined for several plant species (30,47). With certain microbial siderophores such as rhizoferrin and rhodotorulic acid, the reductase may easily cleave iron from the siderophore to allow subsequent uptake by the ferrous iron transporter. However, with the hydroxamate siderophore, ferrioxamine B, which is produced by actinomycetes and u.sed by diverse bacteria and fungi, it has been shown that the iron stress-regulated reductase is not capable... 

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... 

Two fluorescent siderophore analogs, one based on ferrichrome 173 and the second on ferrioxamine 188, were used to study iron transport in the fungus Ustilago maydis that has an uptake system for ferrichrome but lacks a defined ferrioxamine receptor. Nevertheless, ferrioxamine can be utilized by the fungus albeit at a slower rate. 

In S. typhimurium a combination of two concurrent processes, either mechanisms 1 and 3 or mechanism 2, would explain the observed results. The former would account for the rapid phase of iron uptake while the latter would explain the slower penetration rate of the intact chelate. In this organism the iron of ferrioxamine B is again rapidly assimilated, and the chelate enters at a slower pace, but no information on the mechanism can be gleaned from the chromic complexes as they are not transported. It is possible that the active isomer has not been tested in this system. An inspection of molecular models implies that four trans isomers might exist (79). 

Sifleramines. Obsolete name for microbial iron(III) complexes of the trihydroxamate type with growth promoting properties (e.g., ferrioxamines, ferri-chromes). Tlie name siderophores is now established for the low-molecular weight compounds participating in iron transport. 

In addition to the desABCD cluster involved in desferrioxamines B and E biosynthesis two additional genes, desE and cdtB, have been proposed to recognize and transport ferrioxamines B and E (molecules carrying an iron atom), respectively (Tierrafria et al. 2011). Disruption of desE in S. coelicolor results in impaired growth and lack of sporulation whereas supplementation of the impaired mutant with desferrioxamine E triggers actinorhodin production. 

Other iron boxes that appear to bind DmdRl are located upstream of four different coelichelin biosynthesis genes, cchA, cchE, cchJ and cchF. Although sensing and transport of iron-loaded ferrioxamines seem to be exerted by the DesE and CdtB transporters, the molecular mechanisms by which desferrioxamines influence antibiotic biosynthesis is stiU unclear. 

BLM transport systems for ferrioxamine B were also devised based on first coordination shell recognition via ternary complex formation utilizing vacant coordination sites on the Fe(III) center (Fig. 29) (199). The tetra-coordinated substrate complex selectively transported was partially dechelated diaqua-ferrioxamine B and coordinately unsaturated di-hydroxamato iron(III) complexes, which utilized a hydrophobic membrane bound bidentate chelator as a carrier for selective transport. Active transport for these systems was accomplished using a pH gradient (199). 

More significant is the risk of interorgan redistribution. Chelates forming in the hepatocyte may of course be transported into the bile and excreted in the feces. This is generally considered a positive attribute, but may simply reflect a limited ability to exit the cell. For instance, because ferrioxamine enters and exits cells with difficulty, almost all of the iron this agent removes from the body by biliary excretion (30%-50% of the total removed) originates in the hepatocyte (Hershko et al. 1978). Ferrioxamine that does make its way into the circulation from other sources is rapidly cleared by the kidney. On the one hand, this means that removal of iron... 

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