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

218 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

Keywords

  • Biological sciences
  • bioengineering
  • plant sciences

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