, Volume 17, Issue 6, pp 647–654 | Cite as

Ferrichrome in Schizosaccharomyces pombe – an iron transport and iron storage compound

  • Markus Schrettl
  • Günther Winkelmann
  • Hubertus Haas


Schizosaccharomyces pombe has been assumed not to produce siderophores. Nevertheless, the genomic sequence of this fission yeast revealed the presence of siderophore biosynthetic genes for hydroxamates. Applying a bioassay based on an Aspergillus nidulans strain deficient in siderophore biosynthesis, and using reversed-phase HPLC and mass spectrometry analysis, we demonstrate that S. pombe excretes and accumulates intracellularly the hydroxamate-type siderophore ferrichrome. Under iron-limiting conditions, the cellular ferrichrome pool was present in the desferri-form, while under iron-rich conditions, in the ferri-form. In contrast to S. pombe, hydroxamate-type siderophores could not be detected in two other yeast species, Saccharomyces cerevisiae and Candida albicans.

iron ferrichrome siderophores 


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  1. Ardon O, Nudelman R, Caris C, Libman J, Shanzer A, Chen Y, Hadar Y. 1998 Iron uptake in Ustilago maydis: tracking the iron path. J Bacteriol 180, 2021–2026.Google Scholar
  2. Askwith C, Kaplan J. 1997 An oxidase-permease-based iron trans-port system in Schizosaccharomyces pombe and its expression in Saccharomyces cerevisiae. J BiolChe m272, 401–405.Google Scholar
  3. Berbee ML, Carmean DA, Winka K.2000 Ribosomal DNA and res-olution of branching order among the ascomycota: how many nucleotides are enough? Mol Phylogenet Evol 17, 337–344.Google Scholar
  4. Challis GL, Ravel J, Townsend CA. 2000 Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. Chem Biol 7, 211–224.Google Scholar
  5. Eisendle M, Oberegger H, Zadra I, Haas H. 2003 The siderophor system is essential for viability of Aspergillus nidulans: functional analysis of two genes encoding L-ornithine N 5-monooxygenase (sida) and a nonribosomal peptide synthetase (sidC). Mol Microbiol 49, 359–375.Google Scholar
  6. Haas H. 2003 Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage. Appl Microbiol Biotechnol, 62, 316–330.Google Scholar
  7. Haas H, Angermayr K, Stöffler G. 1997 Molecular analysis of a Penicillium chrysogenum GATA factor encoding gene (srep)ex-hibiting significant homology to the Ustilago maydis urbs1 gene. Gene 184, 33–37.Google Scholar
  8. Haas H, Zadra I, Stoffler G, Angermayr K. 1999 The Aspergil-lus nidulans GATA factor SREA is involved in regulation of siderophore biosynthesis and control of iron uptake. J BiolChem 274, 4613–4619.Google Scholar
  9. Haas H, Schoeser M, Lesuisse E, Ernst JF, Parson W, Abt B, Winkelmann G, & Oberegger H. 2003 Characterisation of the As-pergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C. Biochem J 371, 505–513.Google Scholar
  10. Herrero M, de Lorenzo V, Neilands JB. 1988 Nucleotide sequence of the iucD gene of the pColV-K30 aerobactin operon and topo-logy of its product studied with phoA and lacZ gene fusions. J Bacteriol 170, 56–64.Google Scholar
  11. Heckman DS, Geiser DM, Eidell BR, Stauffer RL, Kardos NL, Hedges SB.2001 Molecular evidence for the early colonization of land by fungi and plants. Science 293, 1129–1133.Google Scholar
  12. Heymann P, Ernst JF, Winkelmann G. 1999 Identification of a fungal triacetylfusarinine C siderophore transport gene (TAF1) in Saccharomyces cerevisiae as a member of the major facilitator superfamily. BioMetals 12, 301–306.Google Scholar
  13. Heymann P, Ernst F, Winkelmann G. 2000 Identification and sub-strate specificity of a ferrichrome-type siderophore transporter (Arn1p) in Saccharomyces cerevisiae. FEMS Microbiol. Lett. 186, 221–227.Google Scholar
  14. Heymann P, Gerads M, Schaller M, Dromer F, Winkelmann G, Ernst JF. 2002 The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun 70, 5246–5255.Google Scholar
  15. Ismail A, Bedell GW, Lupan DM. 1985 Siderophore production by the pathogenic yeast, Candida albicans. Biochem Biophys Res Commun 130, 885–891.Google Scholar
  16. Kleinkauf H, Von Dohren H. 1996 A nonribosomal system of peptide biosynthesis. Eur J Biochem 236, 335–351.Google Scholar
  17. Kosman DJ. 2003 Molecular mechanisms of iron uptake in fungi.Mol Microbiol 47, 1185–1197.Google Scholar
  18. Lesuisse E, Simon-Casteras M, Labbe P. 1998 Siderophore-mediated iron uptake in Saccharomyces cerevisiae: The SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily. Microbiology 144, 3455–3462.Google Scholar
  19. Leong SA, Winkelmann G. 1998 Molecular biology of iron trans-port in fungi. Met Ions Biol Syst 35, 147–186.Google Scholar
  20. Matzanke BF. 1994 Iron Storage in Fungi. In: Winkelmann G, Winge DR, eds. Metal Ions in Fungi. Marcel Decker: New York; 179–213.Google Scholar
  21. Matzanke BF, Bill E, Trautwein AX, Winkelmann G. 1987 Role of siderophores in iron storage in spores of Neurospora crassa and Aspergillus ochraceus. J Bacteriol 169, 5873–5876.Google Scholar
  22. Matzanke BF, Bill E, Trautwein AX, Winkelmann G. 1988 Ferricro-cin functions as the main intracellular iron-storage compound in mycelia of Neurospora crassa. Biol Met 1, 18–25.Google Scholar
  23. Mei B, Budde AD, Leong SA. 1993 sid1, a gene initiating siderophore biosynthesis in Ustilago maydis: molecular char-acterization, regulation by iron, and role in phytopathogenicity. Proc Natl Acad Sci USA 90, 903–907.Google Scholar
  24. Moreno S, Klar A, Nurse P. 1991 Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol 194,795–823.Google Scholar
  25. Neilands JB, Konopka K, Schwyn B, Coy M, Francis RT, Paw BH, Bagg A. 1987 Comparative biochemistry of microbial iron as-similation. In: Winkelmann G, Winge DR eds. Iron Transport in Microbes, Plants and Animals. VCH, Weinheim; 3–34.Google Scholar
  26. Neilands JB. 1995 Siderophores: structure and function of microbial iron transport compounds. J Biol Che m270, 26723–26726.Google Scholar
  27. Oberegger H, Schoeser M, Zadra I, Abt B, Haas H. 2001. SREA is involved in regulation of siderophore biosynthesis, utiliz-ation and uptake in Aspergillus nidulans. Mol Microbiol 41, 1077–1089.Google Scholar
  28. Oberegger H, Zadra I, Schoeser M, Abt B, Parson W, Haas H. 2002 Identification of members of the Aspergillus nidulans SREA reg-ulon: genes involved in siderophore biosynthesis and utilization. Biochem Soc T 30, 781–783.Google Scholar
  29. Oberegger H, Eisendle M, Schrettl M, Graessle S, Haas H. 2003 4-phosphopantetheinyl transferase encoding npgA is essential for siderophore biosynthesis in Aspergillus nidulans. Curr Genet 44, 211–215.Google Scholar
  30. Pelletier B, Beaudoin J, Mukai Y, Labbe S. 2002 Fep1, an iron sensor regulating iron transporter gene expression in Schizosac-charomyces pombe. J Biol Che m277, 22950–22958.Google Scholar
  31. Pelletier B, Beaudoin J, Philpott CC, Labbe S. 2003 Fep1 represses expression of the fission yeast Schizosaccharomyces pombe siderophore-iron transport system. Nucleic Acids Res 31, 4332–4344.Google Scholar
  32. Pontecorvo G, Roper JA, Hemmons LM, MacDonald KD, and Bufton AWJ. 1953 The genetics of Aspergillus nidulans. Adv Genet 5, 141–238.Google Scholar
  33. Schwyn B, Neilands JB. 1987. Universal chemical assay for the detection and determination of siderophores. Anal Biochem 160, 47–56.Google Scholar
  34. Stachelhaus T, Mootz HD, Marahiel MA. 1999 The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases. Chem Biol 6, 493–505.Google Scholar
  35. Stehr M, Diekmann H, Smau L, Seth O, Ghisla S, Singh M, Macheroux P. 1998 A hydrophobic sequence motif common to N-hydroxylating enzymes. Trends Biochem Sci 23, 56–57.Google Scholar
  36. van der Helm D, Winkelmann G. 1994 Hydroxamates and polycar-bonates as iron transport agents (siderophores) in fungi. In: Winkelmann G, Winge DR (eds): 'Metal ions in fungi'. New York, N.Y.: Marcel Decker, Inc., pp.39–148.Google Scholar
  37. Van Ho A, McVey Ward D, Kaplan J. 2002 Transition metal transport in yeast. Annu Rev Microbiol 56, 237–261.Google Scholar
  38. Winkelmann G. 2001 Siderophore transport in Fungi. In: Winkel-mann G (ed): Microbial Transport Systems. Weinheim: Wiley-VCH.Google Scholar
  39. Visca P, Ciervo A, Orsi N. 1994 Cloning and nucleotide sequence of the pvdA gene encoding the pyoverdin biosynthetic enzyme L-ornithine N5-oxygenase in Pseudomonas aeruginosa. J Bac-teriol 176, 1128–1140.Google Scholar
  40. Voisard C, Wang J, McEvoy JL, Xu P, Leong SA. 1993 Urbs1, a gene regulating siderophore biosynthesis in Ustilago maydis, encodes a protein similar to the erythroid transcription factor GATA-1. Mol Cell Bio l13, 7091–7100.Google Scholar
  41. Weber T, Marahiel MA. 2001 Exploring the domain structure of modular nonribosomal peptide synthetases. Structure (Camb) 9, R3–9.Google Scholar
  42. Wood V, Gwilliam R, Rajandream MA, Lyne M, Lyne R et al. 2002 The genome sequence of Schizosaccharomyces pombe. Nature 415, 871–880.Google Scholar
  43. Yuan WM, Gentil GD, Budde AD, Leong SA. 2001 Characteriza-tion of the Ustilago maydis sid2 gene, encoding a multidomain peptide synthetase in the ferrichrome biosynthetic gene cluster.J Bacteriol 183s, 4040–4051.Google Scholar
  44. Yun CW, Ferea T, Rashford J, Ardon O, Brown PO, Botstein D, Ka-plan J, Philpott CC. 2000 Desferrioxamine-mediated iron uptake in Saccharomyces cerevisiae. Evidence for two pathways of iron uptake. J Biol Che m275, 10709–10715.Google Scholar
  45. Zhou LW, Haas H, Marzluf GA. 1998 Isolation and characterization of a new gene, sre, which encodes a GATA-type regulatory pro-tein that controls iron transport in Neurospora crassa. Mol Gen Genet 259, 532–540Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Markus Schrettl
    • 1
  • Günther Winkelmann
    • 2
  • Hubertus Haas
    • 1
  1. 1.Department of Molecular BiologyMedical University Innsbruck
  2. 2.A-6020 Innsbruck, Austria. Department of Microbiology & BiotechnologyUniversity of TuebingenTuebingenGermany

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