The seco-iridoid pathway from Catharanthus roseus

K Miettinen; L Dong; N Navrot; T Schneider; V Burlat; J Pollier; L Woittiez; S van der Krol; R Lugan; T Ilc; R Verpoorte; Kirsi-Marja Oksman-Caldentey; E Martinoia; H Bouwmeester; A Goossens; J. Memelink; D. Werck-Reichhart

doi:10.1038/ncomms4606

The seco-iridoid pathway from Catharanthus roseus

K Miettinen
, L Dong
, N Navrot
, T Schneider
, V Burlat
, J Pollier
, L Woittiez
, S van der Krol
, R Lugan
, T Ilc
, R Verpoorte
, Kirsi-Marja Oksman-Caldentey
, E Martinoia
, H Bouwmeester
, A Goossens
, J. Memelink^*
, D. Werck-Reichhart^*

^*Corresponding author for this work

Leiden University
Wageningen University & Research (WUR)
University of Strasbourg
University of Zurich
Université de Toulouse
Ghent University
Philip Morris International (PMI)

Research output: Contribution to journal › Article › Scientific › peer-review

455 Citations (Scopus)

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

Original language	English
Pages (from-to)	3606-3616
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4606
Publication status	Published - 2014
MoE publication type	A1 Journal article-refereed

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Biological sciences
bioengineering
plant sciences

Access to Document

10.1038/ncomms4606

Cite this

Miettinen, K., Dong, L., Navrot, N., Schneider, T., Burlat, V., Pollier, J., Woittiez, L., van der Krol, S., Lugan, R., Ilc, T., Verpoorte, R., Oksman-Caldentey, K.-M., Martinoia, E., Bouwmeester, H., Goossens, A., Memelink, J., & Werck-Reichhart, D. (2014). The seco-iridoid pathway from Catharanthus roseus. Nature Communications, 5, 3606-3616. https://doi.org/10.1038/ncomms4606

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title = "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",

keywords = "Biological sciences, bioengineering, plant sciences",

author = "K Miettinen and L Dong and N Navrot and T Schneider and V Burlat and J Pollier and L Woittiez and \{van der Krol\}, S and R Lugan and T Ilc and R Verpoorte and Kirsi-Marja Oksman-Caldentey and E Martinoia and H Bouwmeester and A Goossens and J. Memelink and D. Werck-Reichhart",

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Miettinen, K, Dong, L, Navrot, N, Schneider, T, Burlat, V, Pollier, J, Woittiez, L, van der Krol, S, Lugan, R, Ilc, T, Verpoorte, R, Oksman-Caldentey, K-M, Martinoia, E, Bouwmeester, H, Goossens, A, Memelink, J & Werck-Reichhart, D 2014, 'The seco-iridoid pathway from Catharanthus roseus', Nature Communications, vol. 5, pp. 3606-3616. https://doi.org/10.1038/ncomms4606

TY - JOUR

T1 - The seco-iridoid pathway from Catharanthus roseus

AU - Miettinen, K

AU - Dong, L

AU - Navrot, N

AU - Schneider, T

AU - Burlat, V

AU - Pollier, J

AU - Woittiez, L

AU - van der Krol, S

AU - Lugan, R

AU - Ilc, T

AU - Verpoorte, R

AU - Oksman-Caldentey, Kirsi-Marja

AU - Martinoia, E

AU - Bouwmeester, H

AU - Goossens, A

AU - Memelink, J.

AU - Werck-Reichhart, D.

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

KW - Biological sciences

KW - bioengineering

KW - plant sciences

U2 - 10.1038/ncomms4606

DO - 10.1038/ncomms4606

M3 - Article

SN - 2041-1723

VL - 5

SP - 3606

EP - 3616

JO - Nature Communications

JF - Nature Communications

ER -

The seco-iridoid pathway from Catharanthus roseus

Abstract

UN SDGs

Keywords

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