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 (Corresponding Author), D Werck-Reichhart (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

179 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 languageEnglish
Article number3606
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 2014
MoE publication typeA1 Journal article-refereed

Fingerprint

Secologanin Tryptamine Alkaloids
Catharanthus
alkaloids
Biosynthesis
Iridoids
biosynthesis
indoles
Alkaloids
genes
Insect Repellents
Genes
Synthetic Biology
Gene encoding
Vinblastine
Phytochemicals
Vincristine
Pharmaceutical Preparations
Agriculture
Availability
Pharmacology

Keywords

  • Biological sciences
  • bioengineering
  • plant sciences

Cite this

Miettinen, K., Dong, L., Navrot, N., Schneider, T., Burlat, V., Pollier, J., ... Werck-Reichhart, D. (2014). The seco-iridoid pathway from Catharanthus roseus. Nature Communications, 5, [3606]. https://doi.org/10.1038/ncomms4606
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, Kirsi-Marja ; Martinoia, E ; Bouwmeester, H ; Goossens, A ; Memelink, J ; Werck-Reichhart, D. / The seco-iridoid pathway from Catharanthus roseus. In: Nature Communications. 2014 ; Vol. 5.
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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",
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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, 3606. https://doi.org/10.1038/ncomms4606

The seco-iridoid pathway from Catharanthus roseus. / 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, Kirsi-Marja; Martinoia, E; Bouwmeester, H; Goossens, A; Memelink, J (Corresponding Author); Werck-Reichhart, D (Corresponding Author).

In: Nature Communications, Vol. 5, 3606, 2014.

Research output: Contribution to journalArticleScientificpeer-review

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

VL - 5

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3606

ER -

Miettinen K, Dong L, Navrot N, Schneider T, Burlat V, Pollier J et al. The seco-iridoid pathway from Catharanthus roseus. Nature Communications. 2014;5. 3606. https://doi.org/10.1038/ncomms4606