Streptomyces pilosus

Deferoxamine derives from the bacterium Streptomyces pilosus. The Ltillmann, Color Atlas of Pharmacology... 

Unlike desferrioxamine analogs designed for specific therapeutic purposes described above, chiral DFO analogs that form conformationally unique complexes with iron(lll) were designed to serve as chemical probes of microbial iron(lll) uptake processes. As mentioned above, ferrioxamine B can form a total of five isomers when binding trivalent metal ions, each as a racemic mixture. Muller and Raymond studied three separate, kinetically inert chromium complexes of desferrioxamine B (N-cis,cis, C-cis,cis and trans isomers), which showed the same inhibition of Fe-ferrioxamine B uptake by Streptomyces pilosus. This result may indicate either that (i) ferrioxamine B receptor in this microorganism does not discriminate between geometrical isomers, or that (ii) ferrioxamine B complexes are conformationally poorly defined and are not optimal to serve as probes. 

Desferrioxamine (DFO-B), the natural siderophore initially isolated from Streptomyces pilosus, is the only iron chelator currently used for clinical treatment of iron-overload disease such as thalassemia, sickle cell anemia and hemochromatosis ° . ... 

To enhance iron excretion, intensive chelation therapy is used. The most successful drug is desferrioxamine B, a powerful Fe3+-chelator produced by the microbe Streptomyces pilosus,6 The formation constant for the Fe(III) complex, called ferrioxamine B, is 103afi. Used in conjunction with ascorbic acid—vitamin C, a reducing agent that reduces Fe3+ to the more soluble Fe2+— desferrioxamine clears several grams of iron per year from an overloaded patient. The ferrioxamine complex is excreted in the urine. 

A main component of the linear ferrioxamine group (63). Reverses inhibition by ferrimycin antibiotics (148) and acts as a growth factor for Microbacterium lacticum (101). From Streptomyces pilosus (8). Also produced by species of Nocardia and Micromonospora, and by a number of species of Streptomyces (148). 

Desferrioxamine (DFO) is a trihydroaminic acid obtained from isolates of Streptomyces pilosus. Since 1963 it has been clinically used as an iron-chelating agent in patients with iron overload [261], DFO effectively chelates trivalent ions such as iron and Al, producing respectively ferrioxamine and aluminox-amine [12, 30, 260-269]. DFO displays rather complicated physicochemical characteristics. Unchelated DFO is a straight chained lipophilic molecule that can penetrate plasma membranes and undergo metabolic breakdown. In contact with Al, it twines itself around the metal to form stable hydrophilic... 

Deferoxamine derives from Streptomyces pilosus. The substance possesses a very high iron-binding capacity but does not withdraw iron from hemoglobin or cytochromes. It is poorly absorbed enterally and must be given parenterally to cause increased excretion of iron. Oral administration is indicated only if enteral absorption of iron is to be curtailed. Unwanted effects include allergic reactions. 

Deferoxamine is a polyhydroxamine acid with specific affinity for iron and, less strongly, aluminium. It is a naturally occurring siderophore produced by Streptomyces pilosus. 

For the last quarter of a century the only selective iron chelator available has been desferrioxamine, Desferal . This material is a sidero-phore secreted by the fungus Streptomyces pilosus in order to scavenge iron from the environment to provide for its nutritional and reproductive needs. The ligand is extremely powerful in respect of picking up ferric iron. Rather fortunately, it has little affinity for other essential biometals such as copper, zinc, calcium or magnesium. 

Deferoxamine is isolated as the iron chelate from Streptomyces pilosus and is treated chemically to obtain the metal-free ligand. Deferoxamine has the desirable properties of a remarkably high affinity for ferric iron K = 10 M ) coupled with a very low affinity for calcium K =10 M" ). Studies in vitro have shown that it removes iron from hemosiderin and ferritin and, to a lesser extent, from transferrin. Iron in hemoglobin or cytochromes is not removed by deferoxamine. 

Several investigations were carried out to remove toxic heavy metal ions from waste water by biosorption. Microbial cells loaded with heavy metals were recovered by flotation, e.g. Streptomyces griseus and S clavuUgerus loaded with Pb [108] and Streptomyces pilosus loaded with Cd [109]. In these flotation processes the microbial cells were dead therefore, they are not considered here. The removal of pyritic sulfur from coal slurries such as coal/water mixtures by Thiobacillus ferrooxidans and recovery of this iron-oxidizing bacterium by flotation is a special technique in the presence of high concentrations of solid particles (see e.g. [110]). The flotation of colloid gas aphrons was used for the recovery of yeast in continuous operation [ 111 ] for the recovery of micro algae, and in the presence of flocculants in batch operation [112]. These special techniques are not discussed here. 

The drug desferrioxamine mentioned at the opening of this chapter is produced by the microbe Streptomyces pilosus. Ferrioxamines are found in the ocean at... 

Schupp T, Waldmeier U, Divers M (1987) Biosynthesis of desferrioxamine B in Streptomyces pilosus evidence for the involvement of lysine decarboxylase. FEMS Microbiol Lett 42 135-139... 

Isol. from Streptomyces pilosus. Siderophore. Chelating agent for iron mobilization used as antidote to iron poisoning also chelates aluminium, of interest with respect to treatment of Alzheimer s disease. Used as 4mAf aq. soln. for photometric detn. of V(F) 480 nm, 3150, pH 1.3), Fe(///). Cryst. -I- IH2O (EtOH aq.). Mp 138-140°. 

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