Regulation of Nitrogen Metabolism in Mycelial Fungi

  • G. A. Marzluf
Part of the The Mycota book series (MYCOTA, volume 3)

Abstract

Nitrogen is found in nearly all of the complex biological macromolecules and is a major component of proteins and of nucleic acids. The mycelial fungi can utilize many different compounds as nitrogen sources, and possess a myriad of different nitrogen catabolic pathways plus a global, hierarchal regulatory system to govern their efficient use. This complex regulatory circuit functions to insure that a constant nitrogen supply is readily available for growth, even in the face of widely different or rapidly changing environments. This chapter will focus primarily upon Aspergillus nidulans and Neurospora crassa, since nearly all of our understanding of nitrogen metabolic regulation in mycelial fungi has been obtained with these two organisms. Many other fungal species almost certainly possess similar nitrogen control systems.

Keywords

Nitrite Assimilation Glutamine Hull NADPH 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andrianopoulos A, Hynes MJ (1990) Sequence and functional analysis of the positively acting regulatory gene amdR from Aspergillus nidulans. Mol Cell Biol 10: 31943203Google Scholar
  2. Arst HN, Scazzocchio C (1985) Formal genetics and molecular biology of the control of gene expression in Aspergillus nidulans. In: Bennett J, Lasure L (eds) Gene manipulations in fungi. Academic Press, Orlando, pp 309–343Google Scholar
  3. Burger G, Strauss J, Scazzocchio C, Lang B (1991a) nirA, the pathway-specific regulatory gene of nitrate assimilation in Aspergillus nidulans, encodes a putative GAL4type zinc finger protein and contains introns in highly conserved regions. Mol Cell Biol 11: 5746–5755Google Scholar
  4. Burger G, Tilburn J, Scazzocchio C (1991b) Molecular cloning and functional characterization of the pathway-specific regulatory gene nirA, which controls nitrate assimilation in Aspergillus nidulans. Mol Cell Biol 11: 795–802PubMedGoogle Scholar
  5. Caddick MX (1992) Characterization of a major Aspergillus regulatory gene, areA. In: Stahl U, Tudzynski P (eds) Molecular biology of filamentous fungi. VCH Press, Weinheim, pp 141–152Google Scholar
  6. Caddick MX, Arst HN, Taylor LH, Johnson RI, Brownlee AG (1986) Cloning of the regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. EMBO J 5: 1087–1090Google Scholar
  7. Caddick MX, Arst HN (1990) Nitrogen regulation in Aspergillus: are two fingers better than one? Gene 95: 123–127PubMedCrossRefGoogle Scholar
  8. Campbell WH, Kinghorn JR (1990) Functional domains of assimilatory nitrate reductases and nitrite reductases. Trends Biochem Sci 15: 315–319PubMedCrossRefGoogle Scholar
  9. Chang LW, Marzluf GA (1979) Nitrogen regulation of uricase synthesis in Neurospora crassa. Mol Gen Genet 176: 385–392CrossRefGoogle Scholar
  10. Chiang TY, Marzluf GA (1994) DNA recognition by the NIT2 nitrogen regulatory protein: importance of the number, spacing, and orientation of GATA core elements and their flanking sequences upon NIT2 binding. Biochemistry 33: 576–582PubMedCrossRefGoogle Scholar
  11. Courey AJ, Tjian R (1988) Analysis of Spl in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell 55: 887–898PubMedCrossRefGoogle Scholar
  12. Cove DJ (1979) Genetic studies of nitrate assimilation in Aspergillus nidulans. Biol Rev 54: 291–327PubMedCrossRefGoogle Scholar
  13. Cunningham TS, Cooper TC (1991) Expression of the DAL80 gene, whose product is homologous to the GATA factors and is a negative regulator of multiple nitrogen catabolic genes in Saccharomyces cerevisiae, is sensitive to nitrogen catabolite repression. Mol Cell Biol 11: 6205–6215PubMedGoogle Scholar
  14. Daniel-Vedele F, Caboche M (1993) A tobacco cDNA clone encoding a GATA-1 zinc finger protein homologous to regulators of nitrogen metabolism in fungi. Mol Gen Genet 240: 365–373PubMedGoogle Scholar
  15. Davis MA, Hynes MJ (1987) Complementation of areAregulatory gene mutations of Aspergillus nidulans by the heterologous regulatory gene nit-2 of Neurospora crassa. Proc Natl Acad Sci USA 84: 3753–3757PubMedCrossRefGoogle Scholar
  16. Diallinas G, Scazzocchio C (1989) A gene coding for the uric acid-xanthine permease of Aspergillus nidulans: inactivational cloning, characterization and sequence of a cis-acting mutation. Genetics 122: 341–350PubMedGoogle Scholar
  17. Dickman MB, Leslie JF (1992) The regulatory gene nit-2 of Neurospora crassa complements a nnu mutant of Gibberella zeae (Fusarium graminearum). Mol Gen Genet 235: 458–462PubMedCrossRefGoogle Scholar
  18. Exley GE, Colandene JD, Garrett RH (1993) Molecular cloning, characterization, and nucleotide sequence of nit-6, the structural gene for nitrite reductase in Neurospora crassa. J Bacteriol 175: 2379–2392PubMedGoogle Scholar
  19. Feng B, Xiao X, Marzluf GA (1993) Recognition of specific nucleotide bases and cooperative DNA binding by the trans-acting nitrogen regulatory protein NIT2 of Neurospora crassa. Nucl Acids Res 21: 3989–3996PubMedCrossRefGoogle Scholar
  20. Fu YH, Marzluf GA (1987a) Characterization of nit-2, the major nitrogen regulatory gene of Neurospora crassa. Mol Cell Biol 7: 1691–1696PubMedGoogle Scholar
  21. Fu YH, Marzluf GA (1987b) Molecular cloning and analysis of the regulation of nit-3, the structural gene for nitrate reductase in Neurospora crassa. Proc Natl Acad Sci USA 84: 8243–8247PubMedCrossRefGoogle Scholar
  22. Fu YH, Marzluf GA (1988) Metabolic control and autogenous regulation of nit-3, the nitrate reductase structural gene of Neurospora crassa. J Bacteriol 170: 657–661PubMedGoogle Scholar
  23. Fu YH, Marzluf GA (1990a) cys-3, the positive-acting sulfur regulatory gene of Neurospora crassa, encodes a sequence-specific DNA binding protein. J Biol Chem 265: 11942–11947Google Scholar
  24. Fu YH, Marzluf GA (1990b) nit-2, the major nitrogen regulatory gene of Neurospora crassa, encodes a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol 10: 1056–1065Google Scholar
  25. Fu YH, Marzluf GA (1990e) nit-2, the major positive-acting nitrogen regulatory gene of Neurospora crassa, encodes a sequence-specific DNA-binding protein. Proc Natl Acad Sci USA 87: 5331–5335Google Scholar
  26. Fu YH, Marzluf GA (1990d) Site-directed mutagenesis of the zinc finger DNA-binding domain of the nitrogen regulatory protein NIT2 of Neurospora. Mol Microbiol 4: 1847–1852PubMedCrossRefGoogle Scholar
  27. Fu YH, Kneesi JY, Marzluf GA (1989a) Isolation of nit-4, the minor nitrogen regulatory gene which mediates nitrate induction in Neurospora crassa. J Bacteriol 171: 4067–4070PubMedGoogle Scholar
  28. Fu YH, Paietta JV, Mannix DG, Marzluf GA (1989b) cys-3, the positive-acting sulfur regulatory gene of Neurospora crassa, encodes a protein with a putative leucine zipper DNA-binding element. Mol Cell Biol 9: 1120–1127Google Scholar
  29. Fu YH, Feng B, Evans S, Marzluf GA (1995) Sequence-specific DNA binding by NIT4, the pathway-specific regulatory protein which mediates nitrate induction in Neurospora. Mol Microbiol 15: 935–942PubMedCrossRefGoogle Scholar
  30. Hanson MA, Marzluf GA (1973) Regulation of a sulfur-controlled protease in Neurospora crassa. J Bacteriol 116: 785–789PubMedGoogle Scholar
  31. Hawker KL, Montague P, Marzluf GA, Kinghorn JR (1991) Heterologous expression and regulation of the Neurospora crassa nit-4 pathway-specific regulatory gene for nitate assmilation in Aspergillus nidulans. Gene 100: 237–240PubMedCrossRefGoogle Scholar
  32. Hull EP, Green PM, Arst HN, Scazzocchio C (1989) Cloning and characterization of the L-proline catabolism gene cluster of Aspergillus nidulans. Mol Microbiol 3: 553–560PubMedCrossRefGoogle Scholar
  33. Hurlburt BK, Garrett RH (1988) Nitrate assimilation in Neurospora crassa: Enzymatic and immunoblot analysis of wild-type and nit mutant protein products in nitrate-induced and glutamine-repressed cultures. Mol Gen Genet 211: 35–40PubMedCrossRefGoogle Scholar
  34. Johnstone IL, McCabe PC, Greaves P, Cole GE, Brow MA, Gurr SJ, Unkles SE, Clutterbach AJ, Kinghorn JR, Innis M (1990) The isolation and characterization of the crnA-niiA-niaD gene cluster for nitrate assimilation in the filamentous fungus Aspergillus nidulans. Gene 90: 181–192PubMedCrossRefGoogle Scholar
  35. Haas H, Bauer B, Redl B, Marzluf GA (1995) Molecular cloning and analysis of nre, the major nitrogen regulatory gene of Penicillium chrysogenum. Curr Genet 27: 150–158PubMedCrossRefGoogle Scholar
  36. Kudla B, Caddick MX, Langdon T, Martinez-Rossi NM, Bennett CF, Sibley S, Davis RW, Arst HN (1990) The regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J 9: 1355–1364Google Scholar
  37. Laurent BC, Treitel MA, Carlson M (1990) The SNF5 protein of Saccharomyces cerevisiae is a glutamine-and proline-rich transcriptional activator that affects expression of a broad spectrum of genes. Mol Cell Biol 10: 5616–5625PubMedGoogle Scholar
  38. Lee HJ, Fu YH, Marzluf GA (1990a) Cloning and analysis of the regulation of the allantoicase gene of Neurospora crassa. Mol Gen Genet 222: 140–144PubMedGoogle Scholar
  39. Lee HJ, Fu YH, Marzluf GA (1990b) Nucleotide sequence and DNA recognition elements of ale, the structural gene which encodes allantoicase, a purine catabolic enzyme of Neurospora crassa. Biochemistry 29: 87798787Google Scholar
  40. Marzluf GA (1981) Regulation of nitrogen metabolism and gene expression in fungi. Microbiol Revs 45: 437–461Google Scholar
  41. Minehart PL, Magasanik B (1991) Sequence and expression of GLN3, a positive nitrogen regulatory gene of Saccharomyces cerevisiae encoding a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol 12: 6216–6226Google Scholar
  42. Nahm BH, Marzluf GA (1987) Induction and de novo synthesis of uricasae, a nitrogen-regulated enzyme in Neurospora crassa. J Bacteriol 170: 1943–1948Google Scholar
  43. Okamoto PM, Fu YH, Marzluf GA (1991) Nit-3, the structural gene of nitrate reductase in Neurospora crassa: nucleotide sequence and regulation of mRNA synthesis and turnover. Mol Gen Genet 227: 213–223Google Scholar
  44. Omichinski JG, Trainor C, Evans T, Gronenborn AM, Clore GM, Felsenfeld G (1993) A small single-“finger” peptide from the erythroid transcription factor GATA-1 binds specifically to DNA as a zinc or iron complex. Proc Natl Acad Sci USA 90: 1676–1680PubMedCrossRefGoogle Scholar
  45. Premakumar R, Sorger GJ, Gooden D (1979) Nitrogen metabolite repression of nitrate reductase in Neurospora crassa. J Bacteriol 137: 1119–1126PubMedGoogle Scholar
  46. Premakumar R, Sorger GJ, Gooden D (1980) Physiological characterization of a Neurospora crassa mutant with impaired regulation of nitrate reductase. J Bacteriol 144: 542–551PubMedGoogle Scholar
  47. Reinert WR, Marzluf GA (1975) Genetic and metabolic control of the purine catabolic enzymes of Neurospora crassa. Mol Gen Genet 139: 39–55PubMedCrossRefGoogle Scholar
  48. Sophianopoulou V, Scazzocchio C (1989) The proline transport protein of Aspergillus nidulans is very similar to amino acid transporters of Saccharomyces cerevisiae. Mol Microbiol 3: 705–714PubMedCrossRefGoogle Scholar
  49. Sophianopoulou V, Suarez T, Diallinas G, Scazzocchio C (1992) Operator-derepressed mutations in the proline utilisation gene cluster of Aspergillus nidulans. Mol Gen Genet 238: 209–213Google Scholar
  50. Sorger GJ, Brown D, Farzannejad M, Guerra A, Jonathan M (1989) Isolation of a gene that down-regulates nitrate assimilation and influences another regulatory gene in the same system. Mol Cell Biol 9: 4113–4117PubMedGoogle Scholar
  51. Stankovich M, Platt A, Caddick MX, Langdon T, Shaffer PM, Arst HN (1993) C-terminal truncation of the transcriptional activator encoded by areA in Aspergillus nidulans results in both loss-of-function and gain-offunction phenotypes. Mol Microbiol 7: 81–87PubMedCrossRefGoogle Scholar
  52. Stewart V, Vollmer SJ (1986) Molecular cloning of nit-2, a regulatory gene required for nitrogen metabolite repression in Neurospora crassa. Gene 46: 291–295PubMedCrossRefGoogle Scholar
  53. Suarez T, Oestreicher N, Kelly J, Ong G, Sankarsingh R, Scazzocchio C (1991a) The uaY positive control gene of Aspergillus nidulans: fine structure, isolation of constitutive mutants and reversion patterns. Mol Gen Genet 230: 359–368PubMedCrossRefGoogle Scholar
  54. Suarez T, Oestreicher N, Penalva MA, Scazzocchio C (1991b) Molecular cloning of the uaY regulatory gene of Aspergillus nidulans reveals a favoured region for DNA insertions. Mol Gen Genet 230: 369–375PubMedCrossRefGoogle Scholar
  55. Tomsett AB, Garrett RH (1981) Biochemical analysis of mutants defective in nitrate assimilation in Neurospora crassa: evidence for authogenous control by nitrate reductase. Mol Gen Genet 184: 183–190PubMedGoogle Scholar
  56. Tomsett AB, Dunn-Coleman NS, Garrett RH (1981) The regulation of nitrate assimilation in Neurospora crassa: the isolation and genetic analysis of nmr-1 mutants. Mol Gen Genet 182: 229–233PubMedCrossRefGoogle Scholar
  57. Tsai SF, Martin DI, Zon LI, D’Andrea AD, Wong GG, Orkin SH (1989) Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature 339: 446–451PubMedCrossRefGoogle Scholar
  58. Tsao TF, Marzluf GA (1976) Genetic and metabolic regulation of purine base transport in Neurospora crassa. Mol Gen Genet 149: 347–355PubMedCrossRefGoogle Scholar
  59. Voisard C, Wang J, McEvoy JL, Peilin X, Leong SA (1993) urbs-1, a gene regulating siderophore biosynthesis in Ustilago maydis, encodes a protein similar to the erythroid transcription factor GATA-1. Mol Cell Biol 13: 7091–7100Google Scholar
  60. Xiao XD, Marzluf GA (1993) Amino-acid substitutions in the zinc finger of NIT2, the nitrogen regulatory protein of Neurospora crassa, alter promoter element recognition. Curr Genet 24: 212–218PubMedCrossRefGoogle Scholar
  61. Xiao X, Fu YH, Marzluf GA (1995) The negative-acting NMR regulatory protein of Neurospora binds to and inhibits the DNA-binding activity of the positive-acting nitrogen regulatory protein NIT2. Biochemistry 34: 8861–8868PubMedCrossRefGoogle Scholar
  62. Yang HY, Evans T (1992) Distinct roles for the two cGATA-1 finger domains. Mol Cell Biol 12: 4562–4570PubMedGoogle Scholar
  63. Young JL, Jarai G, Fu YH, Marzluf GA (1990) Nucleotide sequence and analysis of nmr, a negative-acting regulatory gene in the nitrogen circuit of Neurospora crassa. Mol Gen Genet 222: 120–128PubMedGoogle Scholar
  64. Yuan GF, Marzluf GA (1992) Molecular characterization of mutations of nit-4, the pathway-specific regulatory gene which controls nitrate assimilation in Neurospora crassa. Mol Microbiol 6: 67–73PubMedCrossRefGoogle Scholar
  65. Yuan GF, Fu YH, Marzluf GA (1991) nit-4, a pathway-specific regulatory gene of Neurospora crassa, encodes a protein with a putative binculear zinc DNA-binding domain. Mol Cell Biol 11: 573. 5–5745Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • G. A. Marzluf
    • 1
  1. 1.Department of BiochemistryThe Ohio State UniversityColumbusUSA

Personalised recommendations