, Volume 15, Issue 4, pp 325–339 | Cite as

Chemical aspects of siderophore mediated iron transport

  • Hakim Boukhalfa
  • Alvin L. Crumbliss


In this mini-review we describe selected aspects of the coordination chemistry relevant to siderophore mediated iron transport and bioavailability. Specific emphasis is placed on a discussion of in vitro kinetic and thermodynamic data that are relevant to elucidating possible in vivo mechanisms for environmental iron acquisition by microbial cells.

bioavailability coordination chemistry iron kinetics ligand exchange mechanism metals oxidation-reduction recognition siderophore thermodynamics transport 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albrecht-Gary A-M, Blanc S, Rochel N, Ocaktan AZ, Abdallah MA. 1994 Bacterial iron transport: Coordination properties of pyoverdin paA, a peptidic siderophore of pseudomonas aeruginosa. Inorg Chem 33, 6391-6402.Google Scholar
  2. Albrecht-Gary A-M, Crumbliss AL. 1998 Coordination chemistry of siderophores: Thermodynamics and kinetics of iron chelation and release. Metal Ions Biol Syst 35, 239-327.Google Scholar
  3. Albrecht-Gary A-M, Crumbliss AL. 1999 Siderophore mediated microbial iron bioavailability: A paradigm for specific metal ion transport. In: Scientific Bridges for 2000 and Beyond. Paris: Académie des Sciences, Editions TEC & DOC; pp. 73-89.Google Scholar
  4. Anderegg G, L'Eplattenier F, Schwarzenbach G. 1963 Hydroxamate complexes. III. Iron(III) exchange between sideramines and complexones. A discussion of the formtion constants of the hydroxamate complexes. Helv Chim Acta 46, 1409-1422.Google Scholar
  5. Bickel H, Hall GE, Keller-Schierlein W, Vischer E, Wettstein A. 1960 Stoffwechselprodukte von Actinomyceten 27 Mitteilung. Uber die konstitution von ferrioxamin B. Helv Chim Acta 43, 2129-2138.Google Scholar
  6. Biruš M, Bradic Z, Krznaric G, Kujundži? N, Pribanic M, Wilikins PC, Wilkins RG. 1987 Kinetics of stepwize hydrolysis of ferrioxamine B and of formation of differrioxamine B in acid perchlorate solution. Inorg Chem 26, 1000-1005.Google Scholar
  7. Biruš M, Kujundži? N, Pribani? M 1993. Kinetics of complexation of iron(III) in aqueous solution. Prog React Kinet 18, 171-271.Google Scholar
  8. Boukhalfa H, Brickman TJ, Armstrong SK, Crumbliss AL. 2000 Kinetics and mechanism of iron(III) dissociation from the dihydroxamate siderophores alcaligin and rhodotorulic acid. Inorg Chem 39, 5591-5602.Google Scholar
  9. Boukhalfa H, Crumbliss AL. Unpublished results.Google Scholar
  10. Boukhalfa H, Crumbliss AL. 2000 Multiple-path dissociation mechanism for mono-and dinuclear tris(hydroxamato)iron(III) complexes with dihydroxamic acid ligands in aqueous solution. Inorg Chem 39, 4318-4331.Google Scholar
  11. Boukhalfa H, Crumbliss AL. 2001 Kinetics and mechanism of a catalytic chloride ion effect on the dissociation of model siderophore hydroxamate-iron(III) complexes. Inorg Chem 40, 4183-4190.Google Scholar
  12. Bradbeer C. 1993 The proton motive force drives the outer membrane transport of cobalamin in Escherichia coli. J Bacteriol 175, 3146-3150.Google Scholar
  13. Braun V. 1998 Pumping iron through cell membranes. Science 282: 2202-2203.Google Scholar
  14. Braun V, Hantke K, Köster W. 1998 Bacterial iron transport: Mechanism, genetics and regulation. Metal Ions Biol Syst 35, 67-145.Google Scholar
  15. Buchanan SK, Smith BS, Venkatramani L, Xia D, Esser L, Palnitkar M, Chakraborty R., van der Helm D, Deisenhofer J. 1999 Crystal structure of the outer membrane active transporter FepA from Escherichia coli. Nature Struct Biol 6, 56-63.Google Scholar
  16. Caldwell CD, Crumbliss AL. 1998 Molecular recognition of ferrioxamine B by host-guest complex formation with lasalocid A in chloroform. Inorg Chem 37, 1906-1912.Google Scholar
  17. Carrano CJ, Cooper SR, Raymond KN. 1979 Coordination chemistry of microbial iron transport compounds. 11. Solution equilibrium and electrochemistry of ferric rhodotorulate complexes. J Am Chem Soc 101, 599-604.Google Scholar
  18. Caudle MT, Stevens RD, Crumbliss AL. 1994a Electrospray mass spectrometry study of 1:1 ferric dihydroxamates. Inorg Chem 33, 843-844.Google Scholar
  19. Caudle MT, Stevens RD, Crumbliss AL. 1994b A monomer-todimer shift in a series of 1:1 ferric dihydroxamates probed by electrospray mass spectrometry. Inorg Chem 33, 6111-6115.Google Scholar
  20. Clarke TE, Ku S-Y, Dougan DR, Vogel HJ, Tari LW. 2000 The structure of the ferric siderophore binding protein FhuD complexed with gallichrome. Nature Struct Biol 7, 287-291.Google Scholar
  21. Cooper SR, McArdle JV, Raymond KN. 1978 Siderophore electrochemistry: Relation to intracellular iron release mechanism. Proc Natl Acad Sci USA 75, 3551-3554.Google Scholar
  22. Dhungana S, Crumbliss AL. 2001 Microbial iron transport via a siderophore shuttle: A membrane ion transport paradigm. ChemTracts-Inorg Chem 14, 258-265.Google Scholar
  23. Dhungana S, White PS, Crumbliss AL. 2001 Crystal structure of ferrioxamine B: A comparative analysis and implications for molecular recognition. J Biol Inorg Chem 6, 810-818.Google Scholar
  24. Dhungana S, Heggemann S, Gebhardt P, Möllmann U, Crumbliss AL. 2002 Fe(III) coordination properties of a new saccharide-based exocyclic trihydroxamate analogue of ferrichrome. Inorg. Chem. submitted for publication.Google Scholar
  25. Dodgen HW, Liu G, Hunt JP. 1981 Water exchange with ferric ion and oligomerized iron in acidic aqueous solutions. Inorg Chem 20, 1002-1005.Google Scholar
  26. Ducommun Y, Newman KE, Merbach AE. 1980 High-pressure O-17 NMR evidence for gradual mechanistic change over from Ia to Id for water exchange on divalent octahedal metal ions from manganese(II) to nickel(II). Inorg Chem 19, 3696-3703.Google Scholar
  27. Ferguson AD, Hofmann E, Coulton JW, Diederichs K, Welte W. 1998 Siderophore-mediated iron transport: Crystal structure of FhuA with bound lipopolysaccharide. Science 282, 2215-2220.Google Scholar
  28. Grant M, Jordan RB. 1981 Kinetics of solvent water exchange on iron(III). Inorg Chem 20, 55-60.Google Scholar
  29. Harris WR, Carrano CJ, Raymond KN. 1979 Coordination chemistry of microbial iron transport compounds. 16. Isolation, characterization, and formation constants of ferric aerobactin. J Am Chem Soc 101, 2722-2727.Google Scholar
  30. Helman R, Lawrence GD. 1989 The increase in ferrioxamine B reduction potential with increasing acidity of the medium. J Electroanal Chem (Bioelectrochem Bioenergetics) 22, 187-196.Google Scholar
  31. Hersman L, Lloyd T, Sposito G. 1995 Siderophore-promoted dissolution of hematite. Geochim Cosmochim Acta 59, 3327-3330.Google Scholar
  32. Hersman L, Maurice P, Sposito G. 1996 Iron acquisition from hydrous Fe(III)-oxides by an aerobic Pseudomonas sp. Chem Geol 132, 25-31.Google Scholar
  33. Hersman LE. 2000 The role of siderophores in iron oxide dissolution. In Lovley DR ed Environmental Microbe-Metal Interactions, ASM, Washington DC; 145-157.Google Scholar
  34. Hou Z, Raymond KN, O'Sullivan B, Esker TW, Nishio T. 1998 A Preorganized siderophore: Thermodynamic and structural characterization of alcaligin and bisucaberin, microbial macrocyclic dihydroxamate chelating agents. Inorg Chem 37, 6630-6637.Google Scholar
  35. Hou Z, Sunderland CJ, Nishio T, Raymond KN. 1996 Preorganization of ferric alcaligin, Fe2L3. The first structure of a ferric dihydroxamate siderophore. J Am Chem Soc 118: 5148-5149.Google Scholar
  36. Kadner RJ (1990) Vitamin B12 transport in Escherichia coli: Energy coupling between membranes. Mol Microbiol 4, 2027-2033.Google Scholar
  37. Konetschny-Rapp S, Jung G, Raymond KN, Meiwes J, Zaehner H. 1992 Solution thermodynamics of the ferric complexes of new deferrioxamine siderophores obtained by directed fermentation. J Am Chem Soc 114, 2224-2230.Google Scholar
  38. Larsen RA, Myers PS, Skare JT, Seachord CL, Darveau RP, Postle K. 1996 Identification of TonB homologs in the family enterobacteriaceae and evidence for conservation of TonB-dependent energy transduction complexes. J Bacteriol 178, 1363-1373.Google Scholar
  39. Lee CW, Ecker DJ, Raymond KN. 1985 Coordination chemistry of microbial iron transport compounds. 34. The pH-dependent reduction of ferric enterobactin probed by electrochemical methods and its implications for microbial iron transport. J Am Chem Soc 107, 6920-6923.Google Scholar
  40. Lincoln SN, Merbach AE. 1995 Substitution reactions of solvaled metal ions. Adv Inorg Chem 42, 1-181.Google Scholar
  41. Locher KP, Rees B, Koebnik R., Mitschler A., Moulinier L, Rosenbush JP, Moras D. 1998 Transmembrane signaling across the ligand-gated FhuA receptor: Crystal structures of free and ferrichrome-bound states reveal allosteric changes. Cell 95, 771-778.Google Scholar
  42. Loomis LD, Raymond KN. 1991 Solution equilibria of enterobactin and metal-enterobactin complexes. Inorg Chem 30, 906-911.Google Scholar
  43. Martell AE, Smith RM. 1974, 1975, 1976, 1977, 1982, 1989 Critical Stability Constants. Plenum, New York, Volumes 1-6.Google Scholar
  44. Matzanke BF, Berner I, Bill E, Trautwein AX, Winkelmann G. 1991 Transport and utilization of ferrioxamine-E-bound iron in Erwinia herbicola (Pantoea agglomerans). BioMetals 4, 181-185.Google Scholar
  45. Maurice PA, Vierkorn MA, Hersman LE, Fulghum JE, Ferryman A. 2001 Enhancement of kaolinite dissolution by an aerobic Pseudomonas mendocina bacterium. Geomicrobiol J 18, 21-35.Google Scholar
  46. Monzyk B, Crumbliss AL. 1982 Kinetics and mechanism of the stepwise dissociation of iron(III) from ferrioxamine B in aqueous acid. J Am Chem Soc 104, 4921-4929.Google Scholar
  47. Novicova NM, Novikov VT. 1981 Kinetics of complex formation by iron(III) with thyrone and 2,7-dichlorochromotropic acid. Russ J Inorg Chem 26, 759-760.Google Scholar
  48. Pecoraro VL, Harris WR, Wong GB, Carrano CJ, Raymond KN. 1983 Coordination chemistry of microbial iron transport compounds. 23. Fourier transform infrared spectroscopy of ferric catechoylamide analogues of enterobactin. J Am Chem Soc 105, 4623-4633.Google Scholar
  49. Postle K. 1993 TonB protein and energy transduction between membranes. J Bioenerg Biomembr 25, 591-601.Google Scholar
  50. Raymond KN, Carrano, CJ. 1979 Coordination chemistry and microbial iron transport. Accts. Chem. Res. 12, 183-190.Google Scholar
  51. Raymond KN, Mueller G, Matzanke BF. 1984 Complexation of iron by siderophores. A review of their solution and structural chemistry and biological function. Top Curr Chem 123, 49-102.Google Scholar
  52. Raymond KN, Telford JR. 1995 Siderophore-mediated iron transport in microbes. NATO ASI Ser (Ser C) 459, 25-37.Google Scholar
  53. Schalk IJ, Hennard C, Dugave C, Poole K, Abdallah MA, Pattus F. 2001 Iron-free pyoverdin binds to its outer membrane receport FpvA in Pseudomonas aeroginosa: a new mechanism for membrne iron transport. Mol Microbiol 39, 351-360.Google Scholar
  54. Schalk IJ, Kyslik P, Prome D, van Dorsselaer A, Poole K, Abdallah MA, Pattus F. 1999 Copurification of the FpvA ferric pyoverdin receptor of Pseudomonas aeruginosa with its iron-free ligand: Implications for siderophore-mediated iron transport. Biochem 38, 9357-9365.Google Scholar
  55. Schalk IJ, Abdallah MA, Pattus F. 2002 Recycling of Pyoverdin on the FpvA receptor after ferric pyoverdin uptake and dissociation in Pseudomonas aeruginosa Biochem 41, 1663-1671.Google Scholar
  56. Schwarzenbach G, Schwarzenbach K. 1963 Hydroxamate complexes. I. The stabilities of the iron(III) complexes of simple hydroxamic acids and desferriferrioxamine B. Helv Chim Acta 46, 1390-1400.Google Scholar
  57. Schwarzenbach G, Willi A. 1951 Metallindikatoren III. Die komplexbildung der brenzcatechin-3,5-disulfosaure (=Tiron) mit dem eisen(III)-ion. Helv Chim Acta 34, 528-539.Google Scholar
  58. Sigel A, Sigel H (eds). 1998 Iron Transport and Storage in Microorganisms, Plants and Animals. Metal Ions in Biological Systems, New York: Marcel Dekker, Inc.; Vol 35.Google Scholar
  59. Spasojevi? I, Amstrong SK, Brickman TJ, Crumbliss AL. 1999 Electrochemical behavior of the Fe(III) complexes of the cyclic hydroxamate siderophores alcaligin and desferrioxamine E. Inorg Chem 38, 449-454.Google Scholar
  60. Spasojevi? I, Crumbliss AL. 1998 Bulk liquid membrane transport of ferrioxamine B by neutral and ionizable carriers. J Chem Soc Dalton, 4021-4027.Google Scholar
  61. Spasojevi? I, Crumbliss AL. 1999 pH induced active ('uphill') liquid membrane transport of ferrioxamine B by the ionizable ionophore lasalocid. Inorg Chem 38, 3248-3250.Google Scholar
  62. Spasojevi? I, Crumbliss AL. 2002 Kinetics and mechanism of ferrioxamine E complex formation and dissociation in aqueous acid. Inorg Chem, in preparation.Google Scholar
  63. Spasojevi? I, Boukhalfa H, Stevens RD, Crumbliss AL. 2001 Aqueous solution speciation of Fe(III) complexes with dihydroxamate siderophores alcaligin and rhodotorulic acid and synthetic analogues using electrospray ionization mass spectrometry. Inorg Chem 40, 49-58.Google Scholar
  64. Stintzi A, Barnes C, Xu J, Raymond KN. 2000 Microbial iron transport via a siderophore shuttle: A membrane ion transport paradigm. Proc Natl Acad Sci USA 97, 10691-10696.Google Scholar
  65. Stojiljkovic I, Sirinivasin N. 1997 Neisseria meningitidis TonB, ExbB and ExbD genes: TonB-dependent utilization of protein-bound iron in neisseriae. J Bacteriol 179, 805-812.Google Scholar
  66. Swaddle RW, Merbach AE. 1981 High-pressure oxygen-17 fourier transform NMR spectroscopy. Mechanism of water exchange on iron(III) in acidic aqueous solution. Inorg Chem 20, 4212-4216.Google Scholar
  67. Telford JR, Raymond KN. 1996 Molecular recognition: Receptors for cationic guests. In: Atwood JL, Davies JED, MacNicol DD, Voegtle F eds. Comprehensive Supramolecular Chemistry. Oxford: Elsevier Science; 245-266.Google Scholar
  68. Trzaska SM, Kim M, Bartsch RA, Crumbliss AL. 2001 Optimization of the lariat ether carboxylic acid host structure for a ferrioxamine B guest: Demonstration of a second coordination shell chelate effect. Inorg Chem 40, 5823-5828.Google Scholar
  69. Trzaska SM, Toone EJ, Crumbliss AL. 2000 Microcalorimetric determination of thermodynamic parameters for ionophoresiderophore host-guest complex formation. Inorg Chem 39, 1071-1075.Google Scholar
  70. van der Helm D. 1998 The physical chemistry of bacterial outermembrane siderophore receptor proteins. Metal Ions Biol Syst 35, 355-401.Google Scholar
  71. Wawrousek EF, McArdle JV. 1982 Spectroelectrochemistry of ferrioxamine B, ferriochrome, and ferrichrome A. J Inorg Biochem 17, 169-183.Google Scholar
  72. Winkelmann G (ed). 1991 Handbook of Microbial Iron Chelates. Boca Raton, FL: CRC Press.Google Scholar
  73. Winkelmann G, Carrano CJ. (eds) 1997 Transition Metals in Microbial Metabolism. The Netherlands: Harwood Acad. Publ.Google Scholar
  74. Wirgau JI, Spasojevi? I, Boukhalfa H, Batinic-Haberle I, Crumbliss AL. 2002 Thermodynamics, kinetics and mechanism of the stepwise dissociation and formation of tris(L-lysinehydroxamato) iron(III) in aqueous acid. Inorg Chem 41, 1464-1473.Google Scholar
  75. Wong GB, Kappel MJ, Raymond KN, Matzanke B, Winkelmann G. 1983 Coordination chemistry of microbial iron transport compounds. 24. Characterization of coprogen and ferricrocin, two ferric hydroxamate siderophores. J Am Chem Soc 105, 810-815.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Hakim Boukhalfa
    • 1
  • Alvin L. Crumbliss
    • 1
  1. 1.Department of ChemistryDuke UniversityDurhamUSA

Personalised recommendations