TY - JOUR

T1 - The seco-iridoid pathway from Catharanthus roseus

AU - Miettinen, Karel

AU - Dong, Lemeng

AU - Navrot, Nicolas

AU - Schneider, Thomas

AU - Burlat, Vincent

AU - Pollier, Jacob

AU - Woittiez, Lotte

AU - Van Der Krol, Sander

AU - Lugan, Raphaël

AU - Ilc, Tina

AU - Verpoorte, Robert

AU - Oksman-Caldentey, Kirsi Marja

AU - Martinoia, Enrico

AU - Bouwmeester, Harro

AU - Goossens, Alain

AU - Memelink, Johan

AU - Werck-Reichhart, Danièle

N1 - Funding Information: We are grateful to Richard Twyman for critical reading of the manuscript and to Søren Rosendal Jensen for advice on iridoid substrate synthesis. David Nelson is acknowledged for naming P450 enzymes. The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement number 222716–SMARTCELL. T.I. received funding from the People Programme (Marie Curie Actions) of the European Union’s 7th Framework Programme (FP7/2007–2013) under REA Grant Agreement 289217. Publisher Copyright: © 2014 Macmillan Publishers Limited. All rights reserved.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms4606

DO - 10.1038/ncomms4606

M3 - Journal article

C2 - 24710322

AN - SCOPUS:84955315667

VL - 5

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3606

ER -