1887

Abstract

Sterols, carotenoids and gibberellins are synthesized after the reduction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate in different subcellular compartments of the fungus . Lovastatin inhibits growth in many organisms, presumably because of the inhibition of the synthesis of essential terpenoids. However, in growth of the mycelia and sterol and carotenoid content were not affected by the presence of lovastatin. Nevertheless, lovastatin did inhibit the accumulation of gibberellins in the culture medium; this inhibition, however, was counteracted by the addition of mevalonate to the medium. The conversion of HMG-CoA to mevalonate in cell-free extracts was inhibited by 10 nM lovastatin. Since apparently possesses a single gene for HMG-CoA reductase, as shown by Southern hybridization and PCR amplification, it was concluded that the biosynthesis of sterols, carotenoids and gibberellins shares a single HMG-CoA reductase, but the respective subcellular compartments are differentially accessible to lovastatin.

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1999-10-01
2019-12-07
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References

  1. Avalos, J. & Cerdá-Olmedo, E. ( 1987; ). Carotenoid mutants of Gibberella fujikuroi. Curr Genet 11, 505-511.[CrossRef]
    [Google Scholar]
  2. Avalos, J., Casadesús, J. & Cerdá-Olmedo, E. ( 1985; ). Gibberella fujikuroi mutants obtained with UV radiation and N-methyl-N′-nitro-N-nitrosoguanidine. Appl Environ Microbiol 49, 187-191.
    [Google Scholar]
  3. Basson, M. E., Thorsness, M., Finer-Moore, J., Stroud, R. M. & Rine, J. ( 1988; ). Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate limiting enzyme of sterol biosynthesis. Mol Cell Biol 8, 3797-3808.
    [Google Scholar]
  4. Bejarano, E. R. & Cerdá-Olmedo, E. ( 1992; ). Independence of the carotene and sterol pathways of Phycomyces. FEBS Lett 306, 209-212.[CrossRef]
    [Google Scholar]
  5. Biardi, L. & Krisans, S. K. ( 1996; ). Compartmentalization of cholesterol biosynthesis. Conversion of mevalonate to farnesyl diphosphate occurs in the peroxisomes. J Biol Chem 271, 1784-1788.[CrossRef]
    [Google Scholar]
  6. Bradford, M. M. ( 1976; ). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72, 248-254.[CrossRef]
    [Google Scholar]
  7. Candau, R., Avalos, J. & Cerdá-Olmedo, E. ( 1991; ). Gibberellins and carotenoids in the wild type and mutants of Gibberella fujikuroi. Appl Environ Microbiol 57, 3378-3382.
    [Google Scholar]
  8. Candau, R., Avalos, J. & Cerdá-Olmedo, E. ( 1992; ). Regulation of gibberellin biosynthesis in Gibberella fujikuroi. Plant Physiol 100, 1184-1188.[CrossRef]
    [Google Scholar]
  9. Chappell, J. ( 1995a; ). The biochemistry and molecular biology of isoprenoid metabolism. Plant Physiol 107, 1-6.
    [Google Scholar]
  10. Chappell, J. ( 1995b; ). Biochemistry and molecular biology of the isoprenoid biosynthetic pathway in plants. Annu Rev Plant Physiol Mol Biol 46, 521-547.[CrossRef]
    [Google Scholar]
  11. Coolbaugh, R. C. ( 1983; ). Early stages of gibberellin biosynthesis. In The Biochemistry and Physiology of Gibberellins, pp. 53-98. Edited by A. Crozier. New York: Praeger.
  12. Corrochano, L. M. & Avalos, J. ( 1992; ). Cloning a segment of the gene encoding 3-hydroxy-3-methylglutaryl Coenzyme A reductase in Phycomyces blakesleeanus and Gibberella fujikuroi by the polymerase chain reaction. Exp Mycol 16, 167-171.[CrossRef]
    [Google Scholar]
  13. Domenech, C. E., Giordano, W., Avalos, J. & Cerdá-Olmedo, E. ( 1996; ). Separate compartments for the production of sterols, carotenoids, and gibberellins in Gibberella fujikuroi. Eur J Biochem 239, 720-725.[CrossRef]
    [Google Scholar]
  14. Endo, A. & Hasumi, K. ( 1997; ). Mevinic acids. In Fungal Biotechnology, pp. 162-172. Edited by T. Anke. Weinheim: Chapman & Hall.
  15. Fernández-Martı́n, R., Reyes, F., Domenech, C. E., Cabrera, E., Bramley, P. M., Barrero, A. F., Avalos, J. & Cerdá-Olmedo, E. ( 1995; ). Gibberellin biosynthesis in gib mutants of Gibberella fujikuroi. J Biol Chem 270, 14970-14974.[CrossRef]
    [Google Scholar]
  16. Florin-Christensen, M., Florin-Christensen, J., Garin, C., Isola, E., Brenner, R. R. & Rasmussen, L. ( 1990; ). Inhibition of Trypanosoma cruzi growth and sterol biosynthesis by lovastatin. Biochem Biophys Res Commun 166, 1441-1445.[CrossRef]
    [Google Scholar]
  17. Geissman, T. A., Verbiscar, A. J., Phinney, B. O. & Cragg, G. ( 1966; ). Studies on the biosynthesis of gibberellins from (−)-kaurenoic acid in cultures of Gibberella fujikuroi. Phytochemistry 5, 933-947.[CrossRef]
    [Google Scholar]
  18. Haag, H., Grünberg, B., Weber, C., Vauti, F., Aepfelbacher, M. & Siess, W. ( 1994; ). Lovastatin inhibits receptor-stimulated Ca(2+)-influx in retinoic acid differentiated U937 and HL-60 cells. Cell Signal 6, 735-742.[CrossRef]
    [Google Scholar]
  19. Hampton, R., Dimster-Denk, D. & Rine, J. ( 1996; ). The biology of HMG-CoA reductase: the pros of contra-regulation. Trends Biochem Sci 21, 140-145.[CrossRef]
    [Google Scholar]
  20. Lam, W. L. & Doolittle, W. F. ( 1992; ). Mevinolin-resistant mutations identify a promoter and the gene for a eukaryote-like 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the archaebacterium Haloferax volcanii. J Biol Chem 267, 5829-5834.
    [Google Scholar]
  21. Lewer, P. & MacMillan, J. ( 1983; ). Effect of compactin on the incorporation of mevalonolactone into gibberellic acid by Gibberella fujikuroi. Phytochemistry 22, 602-603.[CrossRef]
    [Google Scholar]
  22. Mende, K., Homann, V. & Tudzynski, B. ( 1997; ). The geranylgeranyl diphosphate synthase gene of Gibberella fujikuroi: isolation and expression. Mol Gen Genet 255, 96-105.[CrossRef]
    [Google Scholar]
  23. Morehead, T. A., Biermann, B. J., Crowell, D. N. & Randall, S. K. ( 1995; ). Changes in protein isoprenylation during the growth of suspension-cultured tobacco cells. Plant Physiol 109, 277-284.
    [Google Scholar]
  24. Peña-Dı́az, J., Montalvetti, A., Camacho, A., Gallego, C., Ruiz-Perez, L. M. & Gonzalez-Pacanowska, D. ( 1997; ). A soluble 3-hydroxy-3-methylglutaryl-CoA reductase in the protozoan Trypanosoma cruzi. Biochem J 324, 619-626.
    [Google Scholar]
  25. Rademacher, W. ( 1997; ). Gibberellins. In Fungal Biotechnology, pp. 193-205. Edited by T. Anke. Weinheim: Chapman & Hall.
  26. Rohmer, M., Knani, M., Simonin, P., Sutter, B. & Sahm, H. ( 1993; ). Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate. Biochem J 295, 517-524.
    [Google Scholar]
  27. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  28. Shapiro, D. J., Nordstrom, J. L., Mitschelen, J. J., Rodwell, V. W. & Schimke, R. T. ( 1974; ). Micro assay for 3-hydroxy-3-methylglutaryl-CoA reductase in rat liver and in L-cell fibroblasts. Biochim Biophys Acta 370, 369-377.[CrossRef]
    [Google Scholar]
  29. Sherman, F., Fink, G. R. & Hicks, J. B. (1986). Laboratory Course Manual for Methods in Yeast Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  30. Shiao, M. S. ( 1983; ). Inhibition of gibberellin biosynthesis in Gibberella fujikuroi and germination of Oryza sativa by mevinolin. Bot Bull Acad Sin 24, 135-143.
    [Google Scholar]
  31. Takahashi, N., Phinney, B. O. & MacMillan, J. (1991). Gibberellins. New York: Springer.
  32. Woitek, S., Unkles, S. E., Kinghorn, J. R. & Tudzynski, B. ( 1997; ). 3-Hydroxy-3-methylglutaryl-CoA reductase gene of Gibberella fujikuroi: isolation and characterization. Curr Genet 31, 38-47.[CrossRef]
    [Google Scholar]
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