The seco-iridoid pathway from Catharanthus roseus
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The seco-iridoid pathway from Catharanthus roseus. / Miettinen, Karel; Dong, Lemeng; Navrot, Nicolas; Schneider, Thomas; Burlat, Vincent; Pollier, Jacob; Woittiez, Lotte; Van Der Krol, Sander; Lugan, Raphaël; Ilc, Tina; Verpoorte, Robert; Oksman-Caldentey, Kirsi Marja; Martinoia, Enrico; Bouwmeester, Harro; Goossens, Alain; Memelink, Johan; Werck-Reichhart, Danièle.
In: Nature Communications, Vol. 5, 3606, 2014.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 280017643