Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

New pathway to polyketides in plants

Abstract

The repertoire of secondary metabolism (involving the production of compounds not essential for growth) in the plant kingdom is enormous, but the genetic and functional basis for this diversity is hard to analyse as many of the biosynthetic enzymes are unknown. We have now identified a key enzyme in the ornamental plant Gerbera hybrida (Asteraceae) that participates in the biosynthesis of compounds that contribute to insect and pathogen resistance. Plants transformed with an antisense construct of gchs2, a complementary DNA encoding a previously unknown function1,2, completely lack the pyrone derivatives gerberin and parasorboside. The recombinant plant protein catalyses the principal reaction in the biosynthesis of these derivatives: GCHS2 is a polyketide synthase that uses acetyl-CoA and two condensation reactions with malonyl-CoA to form the pyrone backbone of thenatural products. The enzyme also accepts benzoyl-CoA to synthesize the backbone of substances that have become of interest as inhibitors of the HIV-1 protease3,4,5. GCHS2 is related to chalcone synthase (CHS) and its properties define a new class of function in the protein superfamily. It appears that CHS-related enzymes are involved in the biosynthesis of a much larger range of plant products than was previously realized.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: HPLC analysis of methanol extracts from leaves.
Figure 2: Biosynthetic pathways.
Figure 3: Thin-layer-chromatographic analysis of radioactive products synthesized by GCHS2 in vitro.

Similar content being viewed by others

References

  1. Helariutta, Y. et al. Chalcone synthase-like genes active during corolla development are differentially expressed and encode enzymes with different catalytic properties in Gerbera hybrida (Asteraceae). Plant Mol. Biol. 28, 47–60 (1995).

    Article  CAS  Google Scholar 

  2. Helariutta, Y. et al. Duplication and functional divergence in the chalcone synthase gene family of Asteraceae: evolution with substrate change and catalytic simplification. Proc. Natl Acad. Sci. USA 93, 9033–9038 (1996).

    Article  ADS  CAS  Google Scholar 

  3. Thaisrivongs, S. et al. Structure-based design of HIV protease inhibitors: 5,6-dihydro-4-hydroxy-2-pyrones as effective, nonpeptidic inhibitors. J. Med. Chem. 39, 4630–4642 (1996).

    Article  CAS  Google Scholar 

  4. Hagen, S. E. et al. Synthesis of 5,6-dihydro-4-hydroxy-2-pyrones as HIV-1 protease inhibitors: the profound effect of polarity on antiviral activity. J. Med. Chem. 40, 3707–3711 (1997).

    Article  CAS  Google Scholar 

  5. Tait, B. D. et al. 4-hydroxy-5,6-dihydropyrones. 2. Potent non-peptide inhibitors of HIV protease. J.Med. Chem. 40, 3781–3792 (1997).

    Article  CAS  Google Scholar 

  6. Schröder, J. Afamily of plant-specific polyketide synthases: facts and predictions. Trends Plant Sci. 2, 373–378 (1997).

    Article  Google Scholar 

  7. Elomaa, P., Helariutta, Y., Kotilainen, M. & Teeri, T. H. Transformation of antisense constructs of thechalcone synthase gene superfamily into Gerbera hybrida: differential effect on the expression of family members. Mol. Breed. 2, 41–50 (1996).

    Article  CAS  Google Scholar 

  8. Nagumo, S., Toyonaga, T., Inoue, T. & Nagai, M. New glucosides of a 4-hydroxy-5-methylcoumarin and a dihydro-α-pyrone from Gerbera Jamesonii hybrida. Chem. Pharm. Bull. (Tokyo) 37, 2621–2623 (1989).

    Article  CAS  Google Scholar 

  9. Cardellina, J. G. I & Meinwald, J. Isolation of parasorbic acid from the cranberry plant, Vaccinum macrocarpon. Phytochemistry 19, 2199–2200 (1980).

    Article  CAS  Google Scholar 

  10. Numata, A. et al. Plant constituents biologically active to insects. VI. Antifeedants for larvae of the yellow butterfly Eurema hecabe mandarina in Osmunda japonica. Chem. Pharm. Bull. (Tokyo) 38, 2862–2865 (1990).

    Article  CAS  Google Scholar 

  11. Tschesche, R., Hoppe, H.-J., Snatzke, G., Wulff, G. & Fehlhaber, H.-W. Über Parasorbosid, den glykosidischen Vorläufer der Parasorbinsäure, aus Vogelbeeren. Chem. Ber. 104, 1420–1428 (1971).

    Article  CAS  Google Scholar 

  12. Pyysalo, H. & Kuusi, T. Phenolic compounds from the berries of mountain ash, Sorbus aucuparia. J.Food Sci. 34, 636–638 (1974).

    Article  Google Scholar 

  13. Buston, H. W. & Roy, S. K. The physiological activity of some simple unsaturated lactones. I. Effect on the growth of certain microorganisms. Arch. Biochem. 22, 1–7 (1949).

    CAS  Google Scholar 

  14. Kuhn, R., Jerchel, D., Moewus, F., Möller, E. F. & Lettré, H. Über die chemische Natur der Blastokoline und ihre Einwirkung auf keimende Samen, Pollenkörner, Hefen, Bacterien, Epithelgewebe und Fibroblasten. Naturwissenschaften 37, 463 (1943).

    Google Scholar 

  15. Oster, U., Blos, I. & Rüdiger, W. Natural inhibitors of germination and growth. IV. Compounds from fruit and seeds of mountain ash (Sorbus aucuparia). Z. Naturforsch. 42c, 1179–1184 (1987).

    Article  Google Scholar 

  16. Moewus, F. & Schader, E. Die Wirkung von Cumarin und Parasorbinsäure auf das Austreiben von Kartoffelknollen. Z. Naturforsch. 6b, 112–115 (1951).

    Article  CAS  Google Scholar 

  17. Yalpani, M., Willecke, K. & Lynen, F. Triacetic acid lactone, a derailment product of fatty acid biosynthesis. Eur. J. Biochem. 8, 495–502 (1969).

    Article  CAS  Google Scholar 

  18. Dimroth, P., Walter, H. & Lynen, F. Biosynthese von 6-Methylsalicylsäure. Eur. J. Biochem. 13, 98–110 (1970).

    Article  CAS  Google Scholar 

  19. Kurosaki, F., Kizawa, Y. & Nishi, A. Derailment product in NADPH-dependent synthesis of a dihydroisocoumarin 6-hydroxymellein by elicitor-treated carrot cell extracts. Eur. J. Biochem. 185, 85–89 (1989).

    Article  CAS  Google Scholar 

  20. Pieper, R., Luo, G., Cane, D. E. & Khosla, C. Cell-free synthesis of polyketides by recombinant erythromycin polyketide synthases. Nature 378, 263–266 (1995).

    Article  ADS  CAS  Google Scholar 

  21. Dimroth, P., Ringelmann, E. & Lynen, F. 6-Methylsalicylic acid synthetase from Penicillium patulum. Some catalytic properties of the enzyme and its relation to fatty acid synthetase. Eur. J. Biochem. 68, 591–596 (1976).

    Article  CAS  Google Scholar 

  22. McInnes, A. G., Yoshida, S. & Towers, G. H. N. Aphenolic glycoside from Psilotum nudum (L) Griseb. Tetrahedron 21, 2939–2946 (1965).

    Article  CAS  Google Scholar 

  23. Schüz, R., Heller, W. & Hahlbrock, K. Substrate specificity of chalcone synthase from Petroselinum hortense. Formation of phloroglucinol derivates from aliphatic substrates. J. Biol. Chem. 258, 6730–6734 (1983).

    Google Scholar 

  24. Zuurbier, K. W. M. et al. 4-Hydroxy-2-pyrone formation by chalcone and stilbene synthase with nonphysiological substrates. Phytochemistry (in the press).

  25. Kreuzaler, F., Light, R. J. & Hahlbrock, K. Flavanone synthase catalyzes CO2exchange and decarboxylation of malonyl-CoA. FEBS Lett. 94, 175–178 (1978).

    Article  CAS  Google Scholar 

  26. Tropf, S., Lanz, T., Rensing, S. A., Schröder, J. & Schröder, G. Evidence that stilbene synthases have developed from chalcone synthases several times in the course of evolution. J. Mol. Evol. 38, 610–618 (1994).

    Article  ADS  CAS  Google Scholar 

  27. Schenk, P. M., Baumann, S., Mattes, R. & Steinbiss, H.-H. Improved high-level expression system for eucaryotic genes in Escherichia coli using T7 RNA polymerase and rare tRNAs. Biotechniques 19, 196–200 (1995).

    CAS  Google Scholar 

  28. Lanz, T., Tropf, S., Marner, F.-J., Schröder, J. & Schröder, G. The role of cysteines in polyketide synthases: site-directed mutagenesis of resveratrol and chalcone synthases, two key enzymes in different plant-specific pathways. J. Biol. Chem. 266, 9971–9976 (1991).

    CAS  Google Scholar 

Download references

Acknowledgements

We thank T. J. Simpson for a sample of authentic 6-methyl-4-hydroxy-2-pyrone, L.Britsch for Fractogel EMD Butyl 650 S, and R. Mattes for E. coli strain RM82 with plasmid pUBS520. The group in Freiburg was supported by a grant from the Deutsche Forschungsgemeinschaft. T.H.T. and P.P. thank the Academy of Finland and the Deutsche Forschungsgemeinschaft, respectively, for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joachim Schröder.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eckermann, S., Schröder, G., Schmidt, J. et al. New pathway to polyketides in plants. Nature 396, 387–390 (1998). https://doi.org/10.1038/24652

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/24652

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing