Advertisement

Synthesis and Biological Evaluation of Fungal Bioregulators of Sterol Biosynthesis

  • Edward J. Parish
  • Patrick K. Hanners
  • W. David Nes

Abstract

Corey published a leading paper in 196 7 demonstrating that 2, 3-iminosqualene inhibited the cyclization of squalene-oxide to lanosterol in a cell-free system1. In the interim years between then and this seventh international plant lipid symposium, four groups-one each in the United States2, Canada3 another in France4 and Italy4, have firmly established the mechanistic and biological importance of using this and structurally related molecules, e.g. 25-azasteroids5, to interfere with fungal sterol biosynthesis which results in diminished growth response. Industry and biotechnology firms have followed suit in recent years designing analogous inhibitors6, 7 which they believe may have potential promise in plant protection. On the premise that specific N-isopentenoids induce alterations in sterol biosynthesis which in turn may create a pathologic state in the structure and function of membranes of pathogenic fungi, we began a chemical synthesis program in 1984 by preparing blockers targeted at fungal lipid biosynthesis.

Keywords

Sterol Biosynthesis Ergosterol Biosynthesis Pentacyclic Triterpenoid Biotechnology Firm Analogous Inhibitors6 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    E.J. Corey, P.R.O. de Montellano, K. Lin, and P.D. 2, 3-Iminosqualene, a potent inhibitor of the enzymc cyclization of 2, 3-oxidosqualene to sterols. J. Amer. Chem. Soc. 89/2797 (1967).CrossRefGoogle Scholar
  2. 2.
    W.J. Pinto and W.R. Nes, Stereochemical specificity of sterols in Saccharomyces cerevisiae. J. Biol. Chem. 258: 4472 (1983).PubMedGoogle Scholar
  3. 3.
    L. Avruch and A.C. Oehlschlager, A direct synthesis of 2, 3-epiminosqualene synthesis 10/622 (1973).Google Scholar
  4. 4.
    A. Rahier, M. Taton, P. Bouvier-Nave, P. Schmitt, P. Benveniste, F. Schuber, A.S. Narula, L. Cattel, C. Anding and P. Place, Design of high energy intermediate analogues to study sterol biosynthesis in higher plants. Lipids 21: 52 (1986).CrossRefGoogle Scholar
  5. 5.
    A.C. Oehlschlager, R.H. Angus, A.M. Pierce, H.D. Pierce and R. Srinivasan, Azasterol inhibition of Δ24 sterol methyltransferase in Saccharomyces cerevisiae. Biochemistry 23: 3582 (1984).PubMedCrossRefGoogle Scholar
  6. 6.
    F. Paltauf, G. Daum, G. Zuder, G. Hogenauer, G. Schulz, and G. Seidl. Squalene and ergosterol biosynthesis in fungi treated with natifine, a new antimycotic agent. Biochim. Biophys. Acta 712: 268 (1982).Google Scholar
  7. 7.
    W.D. Nes, P.H. Le, L.R. Berg, G.W. Patterson and J.L. Kerwin, A comparison of cycloartenol and lanosterol biosynthesis and metabolism by the Oomycetes. Experientia 42: 556 (1986).CrossRefGoogle Scholar
  8. 8.
    W.D. Nes and A.E. Stafford, Evidence for metabolic and functional discrimination of sterols by Phytophthora cactorum. Proc. Natl. Acad. Sci. 80: 3227 (1983).PubMedCrossRefGoogle Scholar
  9. 9.
    W.D. Nes and R.C. Heupel, Physiological requirement for biosynthesis of multiple 24ß-methylsterols in Gibberella fujikuroi. Arch. Biochem. Biophys. 244: 211 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Edward J. Parish
    • 1
    • 3
  • Patrick K. Hanners
    • 1
  • W. David Nes
    • 2
  1. 1.Plant and Fungal Lipid Group, Plant Development and Productivity Research Unit, ARSU.S. Department of AgricultureAlbanyUSA
  2. 2.The Plant and Fungal Lipid Group, Plants Physiology Research UnitThe Richard Russell Res. Lab., U.S. Department of AgricultureAthensUSA
  3. 3.Department of ChemistryAuburn UniversityAuburnUSA

Personalised recommendations