Skip to main content
SpringerLink
Log in

Inhibitors of Phospholipid Biosynthesis

  • Conference paper
Biochemistry of Cell Walls and Membranes in Fungi

Abstract

Antifungal compounds used to prevent or cure fungal diseases should display selective toxicity, i.e. they should inhibit growth of the fungus but not of the host. Selective toxicity may result from a compound affecting a site present in the fungus but not the host, e.g. polyoxins inhibit the biosynthesis of chitin, a polymer present in fungi but not in plants (Hori et al. 1974). Alternatively, a site in the fungus may be more sensitive to a compound than an equivalent site in the host, e.g. the antimitotic compound, carbendazim has a greater affinity for fungal β-tubulin than plant β-tubulin (Davidse 1982). Finally, an antifungal compound may display selective toxicity if its uptake, detoxification or activation in the fungus differs from that in the host (Baldwin 1984).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akatsuka T, Kodama O, Yameda H (1977) A novel mode of action of Kitazin P in Pyricularia oryzae.Agric Biol Chem 41: 2111–2112

    Article  CAS  Google Scholar 

  • Angus WW, Lester RL (1972) Turnover of inositol and phosphorus-containing lipids in Saccharomyces cerevisiae; extracellular accumulation of glycerophosphorylinositol derived from phosphatidylinositol. Arch Biochem Biophys 151: 483–495

    Article  PubMed  CAS  Google Scholar 

  • Bailey JA, Vincent GG, Burden RS (1974) Diterpenes from Nicotiana glutinosa and their effect on fungal growth. J Gen Microbiol 85: 57–64

    PubMed  CAS  Google Scholar 

  • Baldwin BC (1984) Potential targets for the selective inhibition of fungal growth. In: Trinci APJ, Ryley JF (eds) Mode of action of antifungal agents. Cambridge Univ Press, Cambridge, pp 43–62

    Google Scholar 

  • Bowman BJ, Borgeson CE, Bowman EJ (1987) Composition of Neurospora crassa vacuolar membranes and comparison to endoplasmic reticulum, plasma membranes and mitochondrial membranes. Exp Mycol 11: 197–205

    Article  CAS  Google Scholar 

  • Bremner J, Greenberg DM (1961) Methyl transferring enzyme system of microsomes in the biosynthesis of lecithin. Biochim Biophys Acta 46: 205–216

    Article  Google Scholar 

  • Brennan PJ, Lösel DM (1978) Physiology of fungal lipids: selected topics. Adv Microb Physiol 17: 47–179

    Article  PubMed  CAS  Google Scholar 

  • Capdeville Y, Cardosa de Almeida ML, Deregnaucourt C (1987) The membrane-anchor of Paramecium temperature-specific antigens in a glycosylinositol phospholipid. Biochem Biophys Res Commun 147: 1219–1225

    Article  PubMed  CAS  Google Scholar 

  • Carman GM, Matas J (1981) Solubilization of mierosomal-associated phosphatidyl serine and phosphatidylinositol synthase from Saccharomyces cerevisiae. Can J Microbiol 27: 1140–1149

    Article  PubMed  CAS  Google Scholar 

  • Chin J, Bloch K (1988) Phosphatidylcholine synthesis in yeast. J Lipid Res 29: 9–14

    PubMed  CAS  Google Scholar 

  • Choprar A, Khuller GK (1983) Lipid metabolism in fungi. CRC Crit Rev Microbiol 11: 209–271

    Article  Google Scholar 

  • Craig GD, Peberdy JF (1983 a) The mode of action of S-benzyl O,O-diisopropyl phosphorothioate and dicloran on Aspergillus nidulans. Pestic Sci 14: 17–24

    Article  CAS  Google Scholar 

  • Craig GD, Peberdy JF (1983 b) The effect of S-benzyl O,O–diisopropylphosphorothioate (Kitazin) and dicloran on the total lipid, sterol and phospholipids in Aspergillus nidulans. FEMS Microbiol Lett 18: 11–14

    Article  CAS  Google Scholar 

  • Cronan JE, Vagelos PR (1972) Metabolism and function of the membrane phospholipids of Escherichia coli. Biochim Biophys Acta 265: 25–60

    PubMed  CAS  Google Scholar 

  • Culbertson MR, Donahue TF, Henry SA (1976) Control of inositol biosynthesis in Saccharomyces cerevisiae: Properties of a repressible enzyme system in extracts of wild type (Ino+) cells. J Bacteriol 126: 232–242

    PubMed  CAS  Google Scholar 

  • Daum G, Heidorn E, Paltauf F (1986) Intracellular transfer of phospholipids in the yeast, Saccharomyces cerevisiae. Biochim Biophys Acta 878: 93–101

    PubMed  CAS  Google Scholar 

  • Davidse LC (1982) Benzimidazole compounds: selectivity and resistance. In: Dekker J, Georgopolous SG (eds) Fungicide resistance in crop protection. Pudoc, Wagenigen, pp 60–70

    Google Scholar 

  • Dickman MB, Patil SS, Kolattukudy PE (1983) Effects of organophosphorus pesticides on cutinase activity and infection of papayas by Colletotrichum gloeosporoides. Phytopathology 73: 1209–1214

    Article  CAS  Google Scholar 

  • Dittmer JC (1962) Distribution of phospholipids. In: Flortun M, Mason HS (eds) Comparative biochemistry, vol III. Academic Press, London New York, pp 231–264

    Google Scholar 

  • Duran A, Cabib E (1978) Solubilization and partial purification of yeast chitin synthetase. J Biol Chem 253: 4419–4425

    PubMed  CAS  Google Scholar 

  • Fischl AS, Carman GM (1983) Phosphatidylinositol biosynthesis in Saccharomyces cerevisiae: Purification and properties of microsome-associated phosphatidylinositol synthesis. J Bacteriol 154: 304–311

    PubMed  CAS  Google Scholar 

  • Fuller RC, Tatum EL (1956) Inositol phospholipid in Neurospora and its relationship to morphology. Am J Bot 43: 361–365

    Article  CAS  Google Scholar 

  • Galpin MF, Jennings DH, Thornton JD (1977) Hyphal branching in Dendryphiella salina: effect of various compounds and further elucidation of the effect of sorbose and the role of cAMP. Trans Br Mycol Soc 69: 175–182

    Article  Google Scholar 

  • Greenberg ML, Reiner B, Henry SA (1982) Regulatory mutants of inositol biosynthesis in yeast: Isolation of inositol-excreting mutants. Genetics 100: 19–33

    PubMed  CAS  Google Scholar 

  • Hanson BA (1984) Role of inositol-containing sphingolipids in Saccharomyces cerevisiae during inositol starvation. J Bacteriol 159: 837–842

    PubMed  CAS  Google Scholar 

  • Hanson BA, Brody S (1979) Lipid and cell wall changes in an inositol-requiring mutant of Neurospora crassa. J Bacteriol 138: 461–466

    PubMed  CAS  Google Scholar 

  • Hanson BA, Lester RL (1982) Effect of inositol starvation on the in vitro synthesis of mannan and N acetylglucosaminylpyrophosphorydolichol in Saccharomyces cerevisiae. J Bacteriol 151: 334–342

    PubMed  CAS  Google Scholar 

  • Henry SA, Klig LS, Loewy BS (1984) The genetic regulation and coordination of biosynthetic pathways in yeast: amino acid and phospholipid synthesis. Annu Rev Genet 18: 2017–2031

    Article  Google Scholar 

  • Homann MJ, Henry SA, Carman GM (1985) Regulation of CDP-diacylglycerol synthase activity in Saccharomyces cerevisiae. J Bacteriol 163: 1265–1266

    PubMed  CAS  Google Scholar 

  • Hori M, Kakiki K, Misato T (1974) Studies on the mode of action of polyoxins. Part IV. Further studies on the relation of polyoxin structure to chitin synthetase inhibition. Agric Biol Chem 38: 691–698

    Article  CAS  Google Scholar 

  • Horowitz NH, Bonner D, Houlahan T (1945) The utilization of choline analogues by cholineless mutants of Neurospora. J Biol Chem 159: 145–151

    CAS  Google Scholar 

  • Hubbard SC, Brody S (1975) Glycerophospholipid variation in choline and inositol auxotrophs of Neurospora crassa. J Biol Chem 250: 7173–7181

    PubMed  CAS  Google Scholar 

  • Humphreys AM, Gooday GW (1984) Phospholipid requirement of microsomal chitinase from Mucor mucedo. Curr Microbiol 11: 187–190

    Article  CAS  Google Scholar 

  • Iwasa T, Yamamoto H, Shibata M (1970) Studies on validamycins, new antibiotics I: Streptomyces hygroscopicus var limoneus, valdidamycin A producing organism. J Antibiot 23: 595–602

    PubMed  Google Scholar 

  • Iwasa T, Higashide E, Yamamoto H, Shibata M (1971) Studies on validamycins, new antibiotics. II. Production and biological properties of validamycins A and B. J Antibiot 24: 102–113

    Google Scholar 

  • Jejelowo OA, Trinci APJ (1988) Effects of the paramorphogens, 3-O-methylglucose, glucosamine and L-sorbose on the growth and morphology of Botrytis fabae. Trans Br Mycol Soc 91: 653–660

    Article  CAS  Google Scholar 

  • Juretic D (1977) The effect of phosphatidylcholine depletion on biochemical and physical properties of a Neurospora membrane mutant. Biochim Biophys Acta 469: 137–150

    Article  PubMed  CAS  Google Scholar 

  • Kasinathan C, Khuller GK (1983) Biosynthesis of major phospholipids of Microsporum gypseum. Biochim Biophys Acta 752: 187–190

    CAS  Google Scholar 

  • Kates M, Marshall O (1975) Biosynthesis of phosphoglycerides in plants. In: Galliard T, Mercer EI (eds) Recent advances in the chemistry and biochemistry of plant lipids. Academic Press, London New York, pp 115–159

    Google Scholar 

  • Kennedy EP, Weiss SB (1956) The function of cytidine coenzymes in the biosynthesis of phospholipids. J Biol Chem 222: 193–214

    PubMed  CAS  Google Scholar 

  • Kido Y, Nagasato T, Ono K, Fujimoto Y, Uyeda M, Shibata M (1986) Change in a cell-wall component of Rhizoctonia solani inhibited by validamycin. J Antibiot 50: 1519–1525

    CAS  Google Scholar 

  • Kinney A J, Moore TS (1987) Phosphatidylcholine synthesis in castor bean endosperm. I. Metabolism of L-serine. Plant Physiol 84: 78–81

    Article  PubMed  CAS  Google Scholar 

  • Klig LS, Homann M J, Carman GM, Henry SA (1985) Coordinate regulation of phospholipid biosynthesis in Saccharomyces cerevisiae: Pleiotropically constitutive Opi 1 mutant. J Bacteriol 162: 1135–1141

    PubMed  CAS  Google Scholar 

  • Kodaki T, Yamashita S (1987) Yeast phosphatidylethanolamine methylation pathway and characterization of two distinct methyltransferase genes. J Biol Chem 262: 15428–15435

    PubMed  CAS  Google Scholar 

  • Kodama O, Yamada H, Akatsuka T (1979) Kitazin P, inhibitor of phosphatidylcholine biosynthesis in Pyricularia oryzae. Agric Biol Chem 43: 1719–1725

    Article  CAS  Google Scholar 

  • Kodama O, Yamashita K, Akatsuka T (1980) Hinosan inhibition of phosphatidylcholine biosynthesis in Pyricularia oryzae. Agric Biol Chem 44: 1015–1021

    Article  CAS  Google Scholar 

  • Kutchler K, Daum G, Paltauf F (1986) Subcellular and submitochondrial localization of phospholipid-synthesizing enzymes in Saccharomyces cerevisiae. J Bacteriol 165: 901–910

    Google Scholar 

  • Letts VA, Henry SA (1985) Regulation of phospholipid synthesis in phosphatidylserine synthase-deficient (chol) mutants of Saccharomyces cerevisiae. J Bacteriol 163: 560–567

    PubMed  CAS  Google Scholar 

  • Low MG, Ferguson MAJ, Futerman AH, Silman I (1986) Covalently attached phosphatidylinositol as a hydrophobic anchor for membrane proteins. TIPS 11: 212–215

    CAS  Google Scholar 

  • Maeda T, Abe H, Kakiki K, Misato T (1970) Studies on the mode of action of organophosphorus fungicide, Kitazin. Part II. Accumulation of an amino sugar derivative from Kitazin-treated mycelia of Pyricularia oryzae. Agric Biol Chem 34: 700–709

    Article  CAS  Google Scholar 

  • Markham P, Bainbridge BW (1978) A morphological lesion (ballooning) related to a requirement for choline in mutants of Aspergillus nidulans. Proc Soc Gen Microbiol 5: 65

    Google Scholar 

  • Matysiak Z, Radominska-Pyrek A, Chojnacki T (1974) The cytidine mechanism and methylation pathway in the formation of TV–methylated ethanolamine phosphoglycerides in Neurospora crassa. J Mol Cell Biochem 3: 143–151

    Article  CAS  Google Scholar 

  • Montgomery GWG, Goodway GW (1985) Phospholipid–enzyme interactions of chitin synthase of Coprinus cinereus. FEMS Microbiol Lett 27: 29–33

    Article  CAS  Google Scholar 

  • Nikawa J, Yamashita S (1983) 2-Hydroxyethylhydrazine as a potent inhibitor of phospholipid methylation in yeast. Biochim Biophys Acta 751: 201–209

    PubMed  CAS  Google Scholar 

  • Nioh T, Mizushima S (1974) Effect of validamycin on the growth and morphology of Pellicularia sasakii. J Gen Appl Microbiol 20: 373–383

    Article  CAS  Google Scholar 

  • Ohta T, Okuda S, Takahashi H (1977) The relationship between phospholid composition and transport activities of amino acids in Escherichia coli membrane vesicles. Biochim Biophys Acta 466: 44–56

    Article  PubMed  CAS  Google Scholar 

  • Paranjapye VN, Deshusses J, Posternack TH (1964) Sur une méthode simplifiée de dosage microbiologique du MS-inositol. Anal Chim Acta 31: 480–488

    Article  CAS  Google Scholar 

  • Pelech SL, Vance DE (1984) Regulation phosphatidylcholine biosynthesis. Biochim Biophys Acta 779: 217–251

    PubMed  CAS  Google Scholar 

  • Pizer LI, Merlie JP (1973) Effect of serine hydroxymate on phospholipid synthesis in E. coli. J Bacteriol 114: 980–987

    PubMed  CAS  Google Scholar 

  • Pritchard PH, Chiang PK, Cantoni GL, Vance DE (1982) Inhibition of phosphatidylethanolamine- N-methylation by 3-deazaadenosine stimulates the synthesis of phosphatidylcholine via the CDP-choline pathway. J Biol Chem 257: 6362–6367

    PubMed  CAS  Google Scholar 

  • Raetz CRH, Kennedy EP (1972) The association of phosphatidylserine synthetase with ribosomes in extracts of Escherichia coli. J Biol Chem 247: 2008–2014

    PubMed  CAS  Google Scholar 

  • Randon J, Lecompte T, Chignard M, Siess W, Marias G, Dray F, Vargaftig B (1981) Dissociation of platelet activation from transmethylation of their membrane phospholipids. Nature (London) 293: 660–662

    Article  CAS  Google Scholar 

  • Robson GD, Kuhn PJ, Trinci APJ (1989) Effect of validamycin A on the inositol content and branching of Rhizoctonia cerealis and other fungi. J Gen Microbiol 135: 739–750

    CAS  Google Scholar 

  • Rouser G, Fleischer S, Yamamoto A (1970) Two-dimensional thin-layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 5: 494–496

    Article  PubMed  CAS  Google Scholar 

  • Scarborough GA, Nyc JF (1967 a) Properties of a phosphatidylethanolamine-methyltransferase from Neurospora crassa. Biochim Biophys Acta 146: 111–115

    CAS  Google Scholar 

  • Scarborough GA, Nyc JF (1967 b) Methylation of ethanolamine phosphatides by microsomes from normal and mutant strains of Neurospora crassa. J Biol Chem 242: 238–242

    CAS  Google Scholar 

  • Shatkin A J, Tatum EL (1961) The relationship of m-inositol to morphology in Neurospora crassa. Am J Bot 48: 760–771

    Article  CAS  Google Scholar 

  • Sherr S, Byk KC (1971) Choline and serine incorporation into the phospholipids of Neurospora crassa. Biochim Biophys Acta 239: 243–247

    PubMed  CAS  Google Scholar 

  • Shibata M, Uyeda M, Mori K (1980) Reversal of validamycin inhibition by the hyphal extract of Rhizoctonia solani. J Antibiot 34: 447–451

    Google Scholar 

  • Sisler HD (1986) Control of fungal diseases by compounds acting as antipenetrants. Crop Protect 5: 306–313

    Article  CAS  Google Scholar 

  • Sonnenberg ASM, Sietsma JH, Wessels JGH (1985) Spatial and temporal differences in the synthesis of (l→3)-β(l→6)-β linkages in a wall glucan of Schizophyllum commune. Exp Mycol 9: 141–148

    Article  CAS  Google Scholar 

  • Steiner MR, Lester RL (1970) In vitro study of the methylation pathway of phosphatidylcholine synthesis and the regulation of this pathway in Saccharomyces cerevisiae. Biochemistry 9: 63–69

    Article  PubMed  CAS  Google Scholar 

  • Steiner MR, Lester RL (1972) In vitro studies of phospholipid biosynthesis in Saccharomyces cerevisiae. Biochim Biophys Acta 260: 222–243

    PubMed  CAS  Google Scholar 

  • Tatum EL, Barratt RW, Cutter VM (1949) Chemical induction of colonial paramorphs in Neurospora and Syncephalastrum. Science 109: 509–511

    Article  PubMed  CAS  Google Scholar 

  • Trinci APJ (1974) A study of the kinetics of hyphal extension and branch initiation of hyphal extension and branch initiation of fungal mycelia. J Gen Microbiol 81: 225–236

    PubMed  CAS  Google Scholar 

  • Trinci APJ ( 1984 a) Regulation of hyphal branching and hyphal orientation. In: Jennings DH, Rayner ADM (eds) The ecology and physiology of the fungal mycelium. Cambridge Univ Press, Cambridge, pp 22–52

    Google Scholar 

  • Trinci APJ ( 1984 b) Antifungal agents which affect hyphal extension and hyphal branching. In: Trinci APJ, Ryley JF (eds) Mode of action of antifungal agents. Cambridge Univ Press, Cambridge, pp 113–134

    Google Scholar 

  • Trinci APJ (1985) Effect of validamycin A and L-sorbose on the growth and morphology of Rhizoctonia cerealis and Rhizoctonia solani. Exp Mycol 9: 20–27

    Article  CAS  Google Scholar 

  • Trinci APJ, Collinge A (1973) Influence of L-sorbose on the growth and morphology of Neurospora crassa. J Gen Microbiol 78: 179–192

    PubMed  CAS  Google Scholar 

  • Trivedi A, Singhal GS, Prasad R (1983) Effect of phosphatidylserine enrichment on amino acid transport in yeast. Biochim Biophys Acta 729: 85–89

    Article  PubMed  CAS  Google Scholar 

  • Vermeulen CA, Wessels JGH (1983) Evidence for a phospholipid requirement of chitin synthase in Schizophyllum commune. Curr Microbiol 8: 67–71

    Article  CAS  Google Scholar 

  • Waechter CJ, Steiner MR, Lester RL (1969) Regulation of phosphatidylcholine biosynthesis by the methylation pathway in Saccharomyces cerevisiae. J Biol Chem 244: 3419–3422

    PubMed  CAS  Google Scholar 

  • Wakae O, Matsuura K (1975) Characteristics of validamycin as a fungicide for Rhizoctonia disease control. Rev Plant Protect Res 8: 81–92

    CAS  Google Scholar 

  • Weete JD (1980) Lipid biochemistry of fungi and other organisms. Academic Press, London New York

    Google Scholar 

  • Weete JD, Furter R, Hansler E, Rast DM (1985) Cellular and chitosomal lipids of Agaricus bisporus and Mucor rouxii. Can J Microbiol 31: 1120–1126

    Article  CAS  Google Scholar 

  • Wessels JGH, Sietsma JH, Sonnenberg ASM (1983) Wall synthesis and assembly during hyphal morphogenesis in Schizophyllum commune. J Gen Microbiol 129: 1607–1616

    CAS  Google Scholar 

  • Wilson AC, Barran LR (1980) The methylation system for 3-Sn-phosphatidylcholine biosynthesis in Fusarium oxysporum. Can J Microbiol 26: 774–777

    Article  CAS  Google Scholar 

  • Wilson RW, Niederpruem DJ (1967) Cellobiose as a paramorphogen in Schizophyllum commune. Can J Microbiol 16: 629–634

    Article  Google Scholar 

  • Yoshida M, Moriya S, Uesugi Y (1984) Observation of transmethylation from methionine into choline in the intact mycelia of Pyricularia oryzae by 13C NMR under the influence of fungicides. J Pestic Sci 9: 703–708

    Article  CAS  Google Scholar 

  • Zsindely A, Kiss A, Shablik M, Szabolics M, Szabó G (1983) Possible rôle of a regulatory gene product upon the myo-inositol-1-phosphate synthase production in Neurospora crassa. Biochim Biophys Acta 741: 273–278

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Microbiology Group, Department of Cell & Structural Biology, University of Manchester, Stopford Building, Manchester, M13 9Pt, UK

    G. D. Robson, M. Wiebe & A. P. J. Trinci

  2. Sittingbourne Research Centre, Shell Research Ltd, Sittingbourne, Kent, ME9 8AG, UK

    P. J. Kuhn

Authors
  1. G. D. Robson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Wiebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. J. Kuhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. P. J. Trinci
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Sittingbourne Research Centre, Shell Research Ltd., ME9 8AG, Sittingbourne, Kent, UK

    Paul J. Kuhn  & Michael W. Goosey  & 

  2. Microbiology Group Department of Cell & Structural Biology School of Biological Sciences, University of Manchester, M13 9PL, Manchester, UK

    Anthony P. J. Trinci

  3. Dow Agricultural Products, R & D, Letcombe Laboratory, Letcombe Regis, OX12 9JT, Wantage, Oxfordshire, UK

    Michel J. Jung  & Leonard G. Copping  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Robson, G.D., Wiebe, M., Kuhn, P.J., Trinci, A.P.J. (1990). Inhibitors of Phospholipid Biosynthesis. In: Kuhn, P.J., Trinci, A.P.J., Jung, M.J., Goosey, M.W., Copping, L.G. (eds) Biochemistry of Cell Walls and Membranes in Fungi. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74215-6_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74215-6_17

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74217-0

  • Online ISBN: 978-3-642-74215-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation