Siderophores and iron-transport in microorganisms

Iron is an essential element in many biological systems, and in spite of it s abundance (5% of the earth crust), its availability is dramatically limit ed by the very high insolubility of iron(III) at physiological pi-Is where the concentration of free iron(III) is less than 10(-17) M, a value which i s much too low to allow any possible growth to aerobic microorganisms. Iron metabolization by the microorganisms necessitates generally the biosyn thesis of low molecular weight compounds (300 to 2000 Da) called siderophor es. These molecules which are generally excreted into the culture medium, c helate very strongly iron(III), solubilize it and transport it into the cel ls using an ATP-dependent high affinity transport system. For nearly fourty years, the structural studies on siderophores have shown a great diversity of structures for these iron-chelating molecules synthesi zed by microorganisms. These structures are characterized by the presence o f one, two and in most cases, three bidentate chelating groups, generally o xygenated, necessary for the formation of very stable hexacoordinated octah edric complexes between the siderophores and iron(III). These groups are ge nerally either catecholates, or hydroxamates or hydroxyacids, but can be an y other bidentate groups. In what follows several typical examples of siderophores belonging to each of these categories are given. It is clear that considering the very high n umber of siderophores having so many different structures so far isolated a nd characterized (more than 200), we have restricted this report to the mos t representative structures of each category, with a special emphasis to py overdins, the fluorescent peptidic siderophores of the fluorescent pseudomo nads. Similarly the siderophore-mediated iron-transport mechanisms of Gram-negati ve bacteria described therafter will report mainly on those of Escherichia coli with a special emphasis to Pseudomonas when information is available. The pyoverdin-mediated iron-transport in fluorescent pseudomonads implies b iochemical mechanisms which involve signal and energy exchanges between the two membranes across the periplasmic space. The energy transduction mechan ism in the case of the pyoverdin-mediated active transport in P. aeruginosa has not been completely elucidated so far. Nevertheless from the data obta ined for ferric enterobactin and ferrichrome in E. coli, it is plausible th at a common mechanism of transport can take place for all the enterobacteri a. The key element of this mechanism is protein TonB in E. coli, head of a series of TonB proteins having a very close structure and characterized in P. putida WCS358 and P. aeruginosa ATCC 15692. The striking similarities ex isting between the various iron-transport steps in these different bacteria l species is highly in favour of a common energy-dependent siderophore-medi ated iron-transport mechanism in microorganisms.