, Volume 7, Issue 1, pp 3–8 | Cite as

Ferric reductases or flavin reductases?

  • Marc Fontecave
  • Jacques Covès
  • Jean-Louis Pierre


Assimilation of iron by microorganisms requires the presence of ferric reductases which participate in the mobilization of iron from ferrisiderophores. The common structural and catalytic properties of these enzymes are described and shown to be identical to those of flavin reductases. This strongly suggests that, in general, the reduction of iron depends on reduced flavins provided by flavin reductases.


flavin iron reductases 


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  1. Andrews SC, Shipley D, Keen JN, Findlay JBC, Harrison PM, Guest J. 1992 The haemoglobin-like protein (HMP) of Escherichia coli has ferrisiderophore reductase activity and its C-terminal domain shares homology with ferredoxin NADP+ reductases. FEBS Lett 302, 247–252.Google Scholar
  2. Arceneaux JE, Byers BR. 1980 Ferrisiderophore reductase activity in Bacillus megaterium. J Bacteriol 141, 715–721.Google Scholar
  3. Braun V, Hantke K, Eick-Helmerich K, et al. 1987 Iron transport system in Escherichia coli. In: Winkelmann G, van der Helm D, Neilands JB, eds. Iron Transport in Microbes, Plants and Animals. Weinheim: VCH verlagsgesellschaft.Google Scholar
  4. Brown KA, Ratledge C. 1975 Iron transport in Mycobacterium smegmatis: ferrimycobactin reductase (NAD(P)H:ferrimycobactin oxidoreductase), the enzyme releasing iron from its carrier. FEBS Lett 53, 262–266.Google Scholar
  5. Castignetti D, Smarrelli J. 1986 Siderophores, the iron nutrition of plants, and nitrate reductase. FEBS Lett 209, 147–151.Google Scholar
  6. Covès J, Fontecave M. 1993 Reduction and mobilization of iron by a NAD(P)H:flavin oxidoreductase from Escherichia coli. Eur J Biochem 211, 635–641.Google Scholar
  7. Covès J, Nivière V, Eschenbrenner M, Fontecave M. 1993a NADPH-sulfite reductase from Escherichia coli: a flavin reductase participating in the generation of the free radical of ribonucleotide reductase. J Biol Chem 268, 18604–18609.Google Scholar
  8. Covès J, Eschenbrenner M, Fontecave M. 1993b Sulfite reductase of Escherichia coli is a ferrisiderophore reductase. Biochem Biophys Res Commun 192, 1403–1408.Google Scholar
  9. Crichton RR. 1991 In: Burgess J, ed. Inorganic Biochemistry of Iron Metabolism. Ellis Horwood: New York.Google Scholar
  10. Crosa JH. 1989 Genetics and molecular biology of siderophore-mediated iron transport in bacteria. Microbiol Rev 53, 517–530.Google Scholar
  11. Crowley DE, Reid CPP, Szanislo PJ. 1987 Microbial siderophores as sources for plants. In: Winkelmann G, van der Helm D, Neilands JB, eds. Iron Transport in Microbes, Plants and Animals. Weinheim: VCH verlagsgesellschaft.Google Scholar
  12. Dailey HA, Lascelles J. 1977 Reduction of iron and synthesis of protoheme by Spirillum itersonii and other organisms. J Bacteriol 129, 815–820.Google Scholar
  13. Dancis A, Klausner RD, Hinnebusch AG, Barriocanal JG. 1990 Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae. Mol Cell Biol 10, 2294–2301.PubMedGoogle Scholar
  14. Dancis A, Roman DG, Anderson GJ, Hinnebusch AG, Klausner RD. 1992 Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron. Proc Natl Acad Sci USA 89, 3869–3873.Google Scholar
  15. Ernst J, Winkelmann G. 1977 Enzymatic release of iron from sideramines in fungi, NADH:sideramine oxido-reductase in Neurospora crassa. Biochim Biophys Acta 500, 27–41.Google Scholar
  16. Fischer E, Strehlow B, Hartz D, Braun V. 1990 Soluble and membrane-bound ferrisiderophore reductases of Escherichia coli K-12. Arch Microbiol 153, 329–336.Google Scholar
  17. Fontecave M, Eliasson R, Reichard P. 1987 NAD(P)H: flavin oxidoreductase of Escherichia coli: a ferric iron reductase participating in the generation of the free radical of ribonucleotide reductase. J Biol Chem 262, 12325–12331.Google Scholar
  18. Fontecave M, Eliasson R, Reichard P. 1989 Enzymatic regulation of the radical content of the small subunit of Escherichia coli ribonucleotide reductase involving reduction of its redox centers. J Biol Chem 264, 9164–9170.Google Scholar
  19. Gaines CG, Lodge JS, Arceneaux JEL, Byers BR. 1981 Ferrisiderophore reductase activity associated with an aromatic biosynthetic enzyme complex in Bacillus subtilis. J Bacteriol 148 527–533.Google Scholar
  20. Hallé F, Meyer J-M. 1989 Ferripyoverdine-reductase activity in Pseudomonas fluorescens. Biol Met 2, 18–24.Google Scholar
  21. Hallé F, Meyer J-M. 1992a Ferrisiderophore reductases of Pseudomonas: purification, properties and cellular location of the Pseudomonas aeruginosa ferripyoverdine reductase. Eur J Biochem 209, 613–620.Google Scholar
  22. Hallé F, Meyer J-M. 1992d Iron release from ferrisiderophores: a multi-step mechanism involving a NADH/FMN oxidoreductase and a chemical reduction by FMNH2. Eur J Biochem 209, 621–627.Google Scholar
  23. Hasan N, Nester EW. 1978a Purification and characterization of NADPH-dependent flavin reductase: an enzyme required for the activation of chorismate synthase in Bacillus subtilis. J Biol Chem 253, 4987–4992.Google Scholar
  24. Hasan N, Nester EW. 1978b Purification and properties of chorismate synthase from Bacillus subtilis. J Biol Chem 253, 4993–4998.Google Scholar
  25. Hastings JW, Potrikus CJ, Gupta SC, Kurfürst M, Makenson JC. 1985 Biochemistry and physiology of bioluminescent bacteria. Adv Microb Physiol 26, 235–291.Google Scholar
  26. Huyer M, Page WJ. 1989 Ferric reductase activity in Azotobacter vinelandii and its inhibition by Zn2+. J Bacteriol 171, 4031–4037.Google Scholar
  27. Jablonski E, DeLuca M. 1977 Purification and properties of the NADH and NADPH specific FMN oxidoreductases from Beneckea harveyi. Biochemistry 16, 2932–2936.Google Scholar
  28. Jones T, Spencer R, Walsh C. 1978 Mechanism and kinetics of iron release from ferritin by dihydroflavins and dihydroflavin analogues. Biochemistry 17, 4011–4017.Google Scholar
  29. Lascelles J, Burke KA. 1978 Reduction of ferric iron by l-lactate and dl-glycerol-3-phosphate in membrane preparations from Staphylococcus aureus and interactions with the nitrate reductase system. J Bacteriol 134, 585–589.Google Scholar
  30. Lee CY, Szittner RB, Meighen EA. 1991 The lux genes of the luminous bacterial symbiont, Photobacterium leiognathi, of the ponyfish: nucleotide sequence, difference in gene organization, and high expression in mutant Escherichia coli. Eur J Biochem 201, 161–167.Google Scholar
  31. Le Faou AE, Morse SA. 1991 Characterization of a soluble ferric reductase from Neisseria gonorrhoeae. Biol Met 4, 126–131.Google Scholar
  32. Lesuisse E, Crichton RR, Labbe P. 1990 Iron-reductases in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1038, 253–259.Google Scholar
  33. Lo H-S, Reeves RE. 1980 Purification and properties of NADPH:flavin oxidoreductase from Entamoeba histolytica. Mol Biol Parasitol 2, 23–30.Google Scholar
  34. Lodge JS, Gaines CG, Arceneaux JEL, Byers BR. 1982 Ferrisiderophore reductase activity in Agrobacterium tumefaciens. J Bacteriol 149, 771–774.Google Scholar
  35. Michaliszyn GA, Wing SS, Meighen EA. 1977 Purification and properties of a NAD(P)H:flavin oxidoreductase from the luminous bacterium, Beneckea harveyi. J Biol Chem 252, 7495–7499.Google Scholar
  36. Moody MD, Dailey HA. 1985 Ferric iron reductase of Rhodopseudomonas sphaeroides. J Bacteriol 163, 1120–1125.Google Scholar
  37. Neilands JB. 1981 Microbial iron compounds. Annu Rev Biochem 50, 715–731.Google Scholar
  38. Quandt KS, Xu F, Chen P, Hultquist DE. 1991 Evidence that the protein components of bovine erythrocyte green heme binding protein and flavin reductase are identical. Biochem Biophys Res Commun 178, 315–321.Google Scholar
  39. Ramjee MN, Coggins JR, Hawkes TR, Lowe DJ, Thorneley RNF. 1991 Spectrophotometric detection of a modified flavin mononucleotide (FMN) intermediate formed during the catalytic cycle of chorismate synthase. J Am Chem Soc 113, 8566–8567.Google Scholar
  40. Sirivech S, Freiden E, Osaki S. 1974 The release of iron from horse spleen ferritin by reduced flavins. Biochem J 143,311–315.Google Scholar
  41. Spyrou G, Haggard-Ljungquist E, Krook M, Jörnvall H, Nilsson E, Reichard P. 1991 Characterization of the flavin reductase gene (fre) of Escherichia coli and construction of a plasmid for overproduction of the enzyme. J Bacteriol 173, 3673–3679.Google Scholar
  42. Swartzman E, Miyamoto C, Graham A, Meighen E. 1990a Delineation of the transcriptional boundaries of the lux operon of Vibrio harveyi demonstrates the presence of two new lux genes. J Biol Chem 265, 3513–3517.Google Scholar
  43. Swartzman E, Kapoor S, Graham AF, Meighen EA. 1990b A new Vibrio fischeri lux gene precedes a bidirectional termination site for the lux operon. J Bacteriol 172, 6797–6802.Google Scholar
  44. Ulvik RJ, Romslo I. 1981 Reduction of exogenous FMN by isolated rat liver mitochondria: significance to the mobilization of iron ferritin. Biochim Biophys Acta 635, 457–469.Google Scholar
  45. Watanabe H, Hastings JW. 1982 Specificities and properties of three reduced pyridine nucleotide-flavin mono-nucleotide reductases coupling to bacterial luciferase. Mol Cell Biochem 44, 181–187.Google Scholar
  46. Winkelmann G, Huschka HG. 1987 Molecular recognition and transport of siderophores in fungi. In: Winkelmann G, van der Helm D, Neilands JB, eds. Iron Transport in Microbes, Plants and Animals. Weinheim: VCH verlagsgesellschaft.Google Scholar
  47. Winkelmann G, ed. 1991 Handbook of Microbial Iron Chelates, Boca Raton, FL: CRC Press.Google Scholar
  48. Xu F, Quandt KS, Hultquist DE. 1992 Characterization of NADPH-dependent methemoglobin reductase as a heme-binding protein present in erythrocytes and liver. Proc Natl Acad Sci USA 89, 2130–2134.Google Scholar
  49. Yubisui T, Maksuki T, Tanishima K, Takeshita M, Yoneyama Y. 1977 NADPH-flavin reductase in human erythrocytes and the reduction of methemoglobin through flavin by the enzyme. Biochem Biophys Res Commun 76, 174–182.Google Scholar
  50. Yubisui T, Matsuki T, Takeshita M, Yoneyama Y. 1979 Characterization of the purified NADPH-flavin reductase of human erythrocytes. J Biochem 85, 719–728.Google Scholar

Copyright information

© Rapid Communications of Oxford Ltd 1994

Authors and Affiliations

  • Marc Fontecave
    • 1
  • Jacques Covès
    • 1
  • Jean-Louis Pierre
    • 1
  1. 1.Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité, Unité de Recherche Associée au CNRS 332, Université Joseph FourierGrenobleFrance

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