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
The (seco)iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form twolarge families of plant-derived bioactive compounds with a wide spectrum of high-valuepharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used asanticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to highmarket prices and poor availability. Their biotechnological production is hampered by thefragmentary knowledge of their biosynthesis. Here we report the discovery of the last fourmissing steps of the (seco)iridoid biosynthesis pathway. Expression of the eight genesencoding this pathway, together with two genes boosting precursor formation and twodownstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologousproduction of the complex MIA strictosidine. This confirms the functionality of all enzymesof the pathway and highlights their utility for synthetic biology programmes towards asustainable biotechnological production of valuable (seco)iridoids and alkaloids withpharmaceutical and agricultural applications
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