Leiden University Scholarly Publications

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Miettinen, K. (2013)

Elucidation of the secoiridoid pathway in Catharanthus roseus

Doctoral Thesis
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 anti-cancer 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 allowed 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 programs towards a...Show moreThe (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 anti-cancer 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 allowed 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 programs towards a sustainable biotechnological production of valuable (seco)iridoids and alkaloids with pharmaceutical and agricultural applications.Show less
Metabolic engineering
Biosynthesis
Terpenoid indole alkaloids
Iridoids
Catharanthus roseus
All authors
Miettinen, K.
Supervisor
Memelink, J.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Science, Leiden University
Date
2013-10-24