The seco-iridoid pathway from Catharanthus roseus

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.

Abstract

The (seco)iridoids and their monoterpenoid indole alkaloid (MIA) derivatives are plant-derived compounds with pharmaceutical applications. Here, the authors identify the last four missing steps of the (seco)iridoid pathway, which they reconstitute in an alternative plant host to produce the complex MIA, strictosidine.

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Pub. Group

ISSN (Electronic): 2041-1723

Publication date (Electronic): 07 April 2014

Volume: 5

Affiliations

[1 ]Sylvius Laboratory, Institute of Biology Leiden, Leiden University , Sylviusweg 72, PO Box 9505, Leiden 2300 RA, The Netherlands

[2 ]Laboratory of Plant Physiology, Wageningen University, Droevendaalsesteeg 1 , Wageningen 6708 PB, The Netherlands

[3 ]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

[4 ]Institute of Plant Biology, University Zurich , Zollikerstrasse 107, Zurich CH-8008, Switzerland

[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 ]Industrial Biotechnology, VTT Technical Research Centre of Finland , P.O. Box 1000, FI-02044 VTT (Espoo), Finland

[8 ]These authors contributed equally to this work

[9 ]Present address: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel 2000, Switzerland

[10 ]Present address: Plant Production Systems Group, Wageningen University, P.O. Box 430, Wageningen 6700 AK, The Netherlands

Author notes

[a ] werck@ 123456unistra.fr

[b ] j.memelink@ 123456biology.leidenuniv.nl

Article

Publisher Item ID: ncomms4606

DOI: 10.1038/ncomms4606

PMC ID: 3992524

PubMed ID: 24710322

Copyright statement: Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

License:

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Categories

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