The seco-iridoid pathway from Catharanthus roseus.
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.
1] Sylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands [2].
Karel
K
Miettinen
1] Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands [2].
Lemeng
L
Dong
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].
Nicolas
N
Navrot
1] Institute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland [2].
Thomas
T
Schneider
CNRS; UMR 5546, Université de Toulouse; UPS; UMR 5546, Laboratoire de Recherche en Sciences Végétales, BP 42617 Auzeville, Castanet-Tolosan F-31326, France.
Vincent
V
Burlat
Department of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 927, Gent B-9052, Belgium.
Jacob
J
Pollier
1] Institute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland [2].
Lotte
L
Woittiez
Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
Sander
S
van der Krol
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.
Raphaël
R
Lugan
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.
Tina
T
Ilc
Sylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands.
Robert
R
Verpoorte
Industrial Biotechnology, VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT (Espoo), Finland.
Kirsi-Marja
KM
Oksman-Caldentey
Institute of Plant Biology, University Zurich, Zollikerstrasse 107, Zurich CH-8008, Switzerland.
Enrico
E
Martinoia
Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
Harro
H
Bouwmeester
Department of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 927, Gent B-9052, Belgium.
Alain
A
Goossens
Sylvius Laboratory, Institute of Biology Leiden, Leiden University, Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands.
Johan
J
Memelink
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.
Danièle
D
Werck-Reichhart
D030008:Catharanthus / Q000235:genetics / Q000378:metabolism*; D017343:Genes, Plant; D039823:Iridoids / Q000378:metabolism*; D008969:Molecular Sequence Data; D014026:Nicotiana / Q000235:genetics
D039823:Iridoids