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Chemical inhibitors of monogalactosyldiacylglycerol synthases in Arabidopsis thaliana

Nature Chemical Biology volume 7, pages 834–842 (2011)Cite this article

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Abstract

Monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the main lipids in photosynthetic membranes in plant cells. They are synthesized in the envelope surrounding plastids by MGD and DGD galactosyltransferases. These galactolipids are critical for the biogenesis of photosynthetic membranes, and they act as a source of polyunsaturated fatty acids for the whole cell and as phospholipid surrogates in phosphate shortage. Based on a high-throughput chemical screen, we have characterized a new compound, galvestine-1, that inhibits MGDs in vitro by competing with diacylglycerol binding. Consistent effects of galvestine-1 on Arabidopsis thaliana include root uptake, circulation in the xylem and mesophyll, inhibition of MGDs in vivo causing a reduction of MGDG content and impairment of chloroplast development. The effects on pollen germination shed light on the contribution of galactolipids to pollen-tube elongation. The whole-genome transcriptional response of Arabidopsis points to the potential benefits of galvestine-1 as a unique tool to study lipid homeostasis in plants.

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Figure 1: MGDG synthesis in plant cells.
Figure 2: In vitro inhibition of MGDG synthases by galvestines.
Figure 3: Design and strategy for the development of libraries of galvestine analogs.
Figure 4: In planta inhibition of galactolipid synthesis by galvestine-1.
Figure 5: In vitro inhibition of pollen tube elongation by galvestine-1.
Figure 6: Transcriptional effects of galvestine-1 in Arabidopsis.

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Acknowledgements

We thank C. Albrieux, L. Caillot, C. Cataye, G. Merer, J. Revol and A. Zoppé for technical assistance and L. Lafanechère, P. Legrain and C. Vincent for helpful discussions. This work was supported by ANR-05-EMPB-017-01, ANR-06-MDCA-014, ANR-10-BLAN-1524-01 and ANR-2010-JCJC-1606-01 grants from the Agence Nationale de la Recherche, France. C.Y.B. was supported by a Marie Curie International Outgoing Fellowship action from the European Commission.

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Author notes

  1. Cyrille Y Botté, Michael Deligny, Anne-Laure Bonneau, Hélène Hardré, Emmanuelle Dubots & Roman Lopez

    Present address: Present addresses: School of Botany, University of Melbourne, Melbourne, Australia (C.Y.B.); University of Fribourg, Fribourg, Switzerland (E.D.), Flamel Technologies, Lyon, France (H.H.), UCB Pharma, Brussels, Belgium (M.D.), Institut National de la Propriété Industrielle, Paris, France (A.L.B.), Taj-Deloitte, Paris, France (R.L.). .,

Authors and Affiliations

  1. Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique, Université Joseph Fourier Grenoble I, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5168, Institut de Recherches en Technologies et Sciences pour le Vivant, Grenoble, France

    Cyrille Y Botté, Aymeric Roccia, Nadia Saïdani, Hélène Hardré, Yoshiki Yamaryo-Botté, Juliette Jouhet, Emmanuelle Dubots, Karen Loizeau, Olivier Bastien, Jacques Joyard, Denis Falconet, Maryse A Block & Eric Maréchal

  2. School of Botany, University of Melbourne, Parkville, Victoria, Australia

    Cyrille Y Botté

  3. Centre National de la Recherche Scientifique, Université Joseph Fourier Grenoble I, Unité Mixte de Recherche 5163, Institut Jean Roget, Grenoble, France

    Cyrille Y Botté

  4. Commissariat à l'Energie Atomique, Institut de Biologie et Technologies de Saclay, Laboratoire de Chimie Bioorganique, Gif-sur-Yvette, France

    Michael Deligny, Anne-Laure Bonneau, Jean-Christophe Cintrat, Bernard Rousseau & Roman Lopez

  5. Centre National de la Recherche Scientifique, Université Montpellier II, Unité Mixte de Recherche 5235, Montpellier, France

    Nadia Saïdani

  6. Centre National de la Recherche Scientifique, Centre de Biophysique Moléculaire, Orléans, France

    Samia Aci

  7. Centre National de la Recherche Scientifique, Université Montpellier II, Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier, Montpellier, France

    Laurent Bréhélin

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Contributions

A.-L.B., A.R., C.Y.B., D.F., E.D., E.M., H.H., J.-C.C., J. Jouhet, M.A.B., M.D., N.S. and Y.Y.-B. performed experiments. B.R. and R.L. designed libraries. S.A. performed chemoinformatic analyses. K.L. and E.M. designed transcriptomic experiments. J. Joyard, M.A.B. and E.M. analyzed transcriptomic data. O.B. and L.B. performed statistical analyses. E.M. designed most experiments and wrote the manuscript with the help of all authors.

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Correspondence to Eric Maréchal.

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The authors have filed a patent on the MGDG synthase inhibitors described in the paper.

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Botté, C., Deligny, M., Roccia, A. et al. Chemical inhibitors of monogalactosyldiacylglycerol synthases in Arabidopsis thaliana. Nat Chem Biol 7, 834–842 (2011). https://doi.org/10.1038/nchembio.658

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