2. Academic Validation
  3. The seco-iridoid pathway from Catharanthus roseus

The seco-iridoid pathway from Catharanthus roseus

  • Nat Commun. 2014 Apr 7:5:3606. doi: 10.1038/ncomms4606.
Karel Miettinen 1,  Lemeng Dong 2,  Nicolas Navrot 3,  Thomas Schneider 4,  Vincent Burlat 5,  Jacob Pollier 6,  Lotte Woittiez 4,  Sander van der Krol 7,  Raphaël Lugan 8,  Tina Ilc 8,  Robert Verpoorte 9,  Kirsi-Marja Oksman-Caldentey 10,  Enrico Martinoia 11,  Harro Bouwmeester 7,  Alain Goossens 6,  Johan Memelink 9,  Danièle Werck-Reichhart 8
Affiliations

Affiliations

  • 1 1] Sylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands [2].
  • 2 1] Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands [2].
  • 3 1] Institut de Biologie Moléculaire des Plantes, Unité Propre de Recherche 2357 du Centre National de la Recherche Scientifique, Université de Strasbourg, 28 rue Goethe, Strasbourg 67000, France [2].
  • 4 1] Institute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland [2].
  • 5 CNRS; UMR 5546, Université de Toulouse; UPS; UMR 5546, Laboratoire de Recherche en Sciences Végétales, BP 42617 Auzeville, Castanet-Tolosan F-31326, France.
  • 6 Department of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 927, Gent B-9052, Belgium.
  • 7 Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
  • 8 Institut de Biologie Moléculaire des Plantes, Unité Propre de Recherche 2357 du Centre National de la Recherche Scientifique, Université de Strasbourg, 28 rue Goethe, Strasbourg 67000, France.
  • 9 Sylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands.
  • 10 Industrial Biotechnology, VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT (Espoo), Finland.
  • 11 Institute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland.
PMID: 24710322 DOI: 10.1038/ncomms4606
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.

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