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The seco-iridoid pathway from Catharanthus roseus

Author

Listed:
  • Karel Miettinen

    (Sylvius Laboratory, Institute of Biology Leiden, Leiden University)

  • Lemeng Dong

    (Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1)

  • Nicolas Navrot

    (Institut de Biologie Moléculaire des Plantes, Unité Propre de Recherche 2357 du Centre National de la Recherche Scientifique, Université de Strasbourg)

  • Thomas Schneider

    (Institute of Plant Biology, University Zurich
    Present address: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel 2000, Switzerland)

  • Vincent Burlat

    (CNRS; UPS; UMR 5546, Laboratoire de Recherche en Sciences Végétales
    UMR 5546, Université de Toulouse)

  • Jacob Pollier

    (Ghent University)

  • Lotte Woittiez

    (Institute of Plant Biology, University Zurich
    Present address: Plant Production Systems Group, Wageningen University, P.O. Box 430, Wageningen 6700 AK, The Netherlands)

  • Sander van der Krol

    (Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1)

  • Raphaël Lugan

    (Institut de Biologie Moléculaire des Plantes, Unité Propre de Recherche 2357 du Centre National de la Recherche Scientifique, Université de Strasbourg)

  • Tina Ilc

    (Institut de Biologie Moléculaire des Plantes, Unité Propre de Recherche 2357 du Centre National de la Recherche Scientifique, Université de Strasbourg)

  • Robert Verpoorte

    (Sylvius Laboratory, Institute of Biology Leiden, Leiden University)

  • Kirsi-Marja Oksman-Caldentey

    (Industrial Biotechnology, VTT Technical Research Centre of Finland)

  • Enrico Martinoia

    (Institute of Plant Biology, University Zurich)

  • Harro Bouwmeester

    (Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1)

  • Alain Goossens

    (Ghent University)

  • Johan Memelink

    (Sylvius Laboratory, Institute of Biology Leiden, Leiden University)

  • Danièle Werck-Reichhart

    (Institut de Biologie Moléculaire des Plantes, Unité Propre de Recherche 2357 du Centre National de la Recherche Scientifique, Université de Strasbourg)

Abstract

The (seco)iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco)iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco)iridoids and alkaloids with pharmaceutical and agricultural applications.

Suggested Citation

  • Karel Miettinen & Lemeng Dong & Nicolas Navrot & Thomas Schneider & Vincent Burlat & Jacob Pollier & Lotte Woittiez & Sander van der Krol & Raphaël Lugan & Tina Ilc & Robert Verpoorte & Kirsi-Marja Ok, 2014. "The seco-iridoid pathway from Catharanthus roseus," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4606
    DOI: 10.1038/ncomms4606
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    Cited by:

    1. Néstor J. Hernández Lozada & Benke Hong & Joshua C. Wood & Lorenzo Caputi & Jérôme Basquin & Ling Chuang & Maritta Kunert & Carlos E. Rodríguez López & Chloe Langley & Dongyan Zhao & C. Robin Buell & , 2022. "Biocatalytic routes to stereo-divergent iridoids," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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