The seco-iridoid pathway from Catharanthus roseus

• Published in: Nature communications Vol. 5; no. 1; p. 3606
• Main Authors: Miettinen, Karel, Dong, Lemeng, Navrot, Nicolas, Schneider, Thomas, Burlat, Vincent, Pollier, Jacob, Woittiez, Lotte, van der Krol, Sander, Lugan, Raphaël, Ilc, Tina, Verpoorte, Robert, Oksman-Caldentey, Kirsi-Marja, Martinoia, Enrico, Bouwmeester, Harro, Goossens, Alain, Memelink, Johan, Werck-Reichhart, Danièle
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.04.2014; Nature Publishing Group; Nature Pub. Group
• Subjects: 14/19; 14/32; 38/39; 42; 42/109; 631/449/1736; 631/61/338/318; 631/92/349; 82; 82/58; 82/80; 82/83; Bioactive compounds; Biochemistry; Biochemistry, Molecular Biology; Biosynthesis; Biotechnology; Botanics; Catharanthus - genetics; Catharanthus - metabolism; Chemical Sciences; cytochrome-p450; enzyme; expression; Genes, Plant; Genomics; Humanities and Social Sciences; indole alkaloid biosynthesis; Iridoids - metabolism; Life Sciences; Medicinal Chemistry; Molecular Sequence Data; multidisciplinary; Nicotiana - genetics; plants; proteins; rauwolfia-serpentina; Science; Science (multidisciplinary); statistical-model; subcellular organization; synthase; Vegetal Biology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4606

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 monoterpenoid indole alkaloid (MIA) derivatives are plant-derived compounds with pharmaceutical applications. Here, the authors identify the last four missing steps of the (seco)iridoid pathway, which they reconstitute in an alternative plant host to produce the complex MIA, strictosidine.