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(+)-7-iso-Jasmonoyl-L-isoleucine is the endogenous bioactive jasmonate

Nature Chemical Biology volume 5, pages 344–350 (2009)Cite this article

Abstract

Hormone-triggered activation of the jasmonate signaling pathway in Arabidopsis thaliana requires SCFCOI1-mediated proteasome degradation of JAZ repressors. (−)-JA-L-Ile is the proposed bioactive hormone, and SCFCOI1 is its likely receptor. We found that the biological activity of (−)-JA-L-Ile is unexpectedly low compared to coronatine and the synthetic isomer (+)-JA-L-Ile, which suggests that the stereochemical orientation of the cyclopentanone-ring side chains greatly affects receptor binding. Detailed GC-MS and HPLC analyses showed that the (−)-JA-L-Ile preparations currently used in ligand binding studies contain small amounts of the C7 epimer (+)-7-iso-JA-L-Ile. Purification of each of these molecules demonstrated that pure (−)-JA-L-Ile is inactive and that the active hormone is (+)-7-iso-JA-L-Ile, which is also structurally more similar to coronatine. In addition, we show that pH changes promote conversion of (+)-7-iso-JA-L-Ile to the inactive (−)-JA-L-Ile form, thus providing a simple mechanism that can regulate hormone activity through epimerization.

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Figure 1: Coronatine promotes COI1-JAZ3 interaction.
Figure 2: (+)-JA-L-Ile is a highly active jasmonate.
Figure 3: (+)-7-iso-JA-L-Ile is the active hormone form, and epimerization to (−)-JA-L-Ile inactivates the hormone.
Figure 4: Methyl esterification reduces hormone activity.

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Acknowledgements

We thank C. Castresana, J.A. Garcia, J. Paz-Ares, V. Rubio and members of the R.S. lab for critical reading of the manuscript and stimulating discussions. We also thank X.-W. Deng (Yale University), who kindly provided seeds for the transgenic plants expressing COI1-flag on a Col-0 background. Vectors pGBKT7gateway and pGADT7gateway were developed by M. Boter (Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas), and the JAZ9 pDONR clone was kindly supplied by J.M. Chico (Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas). We are grateful to R. González and G. Hamberg for technical assistance and to C. Mark for editorial assistance. Chemical structures for the graphical abstract were kindly supplied by A. Segura and F. Pazos. This work was financed by grants to R.S. from the Spanish Ministerio de Ciencia y Tecnología (BIO2004-02502, BIO2007-66935, GEN2003-20218-C02-02 and CSD2007-00057-B) and from the Comunidad de Madrid (GR/SAL/0674/2004). S.F. was supported by postdoctoral fellowships from the Portuguese Foundation for Science and Technology (BPD/21045/2004) and from the Spanish Ministerio de Educación y Ciencia (JAEDoc015). A.C. was supported by a Juan de la Cierva Fellowship from the Spanish Ministerio de Educación y Ciencia and a European Molecular Biology Organization Long-Term Fellowship. B.A. received postdoctoral fellowships from the European Union (CRISP project HPRN-CT-2000-00093) and the Spanish Ministerio de Educación y Ciencia (GEN2003-20218-C02-02).

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Authors and Affiliations

  1. Departamento de Genética Molecular de Plantas, Centro Nacional de Biotecnología-CSIC, Campus Universidad Autónoma, Madrid, Spain

    Sandra Fonseca, Andrea Chini, Bruce Adie & Roberto Solano

  2. Division of Physiological Chemistry II, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm, Sweden

    Mats Hamberg

  3. Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Halle, Germany

    Andrea Porzel

  4. Department of Natural Product Biotechnology, Leibniz-Institute of Plant Biochemistry, Halle, Germany

    Robert Kramell, Otto Miersch & Claus Wasternack

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Contributions

S.F. performed all pulldown experiments and phenotypic analyses. A.C. and B.A. performed all yeast two-hybrid experiments. M.H. synthesized and purified compounds 6, 8, 10, 11, 12 and 18, wrote the corresponding results and methods sections and corrected the manuscript. A.P. made NMR analyses. R.K. and O.M. provided the compounds described in Supplementary Table 1 (except 8, 11, 12 and 18). C.W. supervised work by A.P., R.K. and O.M. and corrected the manuscript. R.S. designed experiments, supervised the work and wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Roberto Solano.

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Fonseca, S., Chini, A., Hamberg, M. et al. (+)-7-iso-Jasmonoyl-L-isoleucine is the endogenous bioactive jasmonate. Nat Chem Biol 5, 344–350 (2009). https://doi.org/10.1038/nchembio.161

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