The seco-iridoid pathway from Catharanthus roseus.
Miettinen K1] Sylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands [2].
Dong L1] Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands [2].
Navrot N1] 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].
Schneider T1] Institute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland [2].
Burlat VCNRS; UMR 5546, Université de Toulouse; UPS; UMR 5546, Laboratoire de Recherche en Sciences Végétales, BP 42617 Auzeville, Castanet-Tolosan F-31326, France.
Pollier JDepartment of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 927, Gent B-9052, Belgium.
Woittiez L1] Institute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland [2].
van der Krol SLaboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
Lugan RInstitut 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.
Ilc TInstitut 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.
Verpoorte RSylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands.
Oksman-Caldentey KMIndustrial Biotechnology, VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT (Espoo), Finland.
Martinoia EInstitute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland.
Bouwmeester HLaboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
Goossens ADepartment of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 927, Gent B-9052, Belgium.
Memelink JSylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands.
Werck-Reichhart DInstitut 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.
English
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.