The seco-iridoid pathway from Catharanthus roseus

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 Oksman-Caldentey, Enrico Martinoia, Harro Bouwmeester, Alain Goossens, Johan Memelink () and Danièle Werck-Reichhart ()
Additional contact information
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
Vincent Burlat: CNRS; UPS; UMR 5546, Laboratoire de Recherche en Sciences Végétales
Jacob Pollier: Ghent University
Lotte Woittiez: Institute of Plant Biology, University Zurich
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

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4606

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