Dual Catalytic Activity of a Cytochrome P450 Controls Bifurcation at a Metabolic Branch Point of Alkaloid Biosynthesis in Rauwolfia serpentina

Plants create tremendous chemical diversity from a single biosynthetic intermediate. In plant‐derived ajmalan alkaloid pathways, the biosynthetic intermediate vomilenine can be transformed into the anti‐arrhythmic compound ajmaline, or alternatively, can isomerize to form perakine, an alkaloid with...

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Bibliographic Details
Published in:Angewandte Chemie 2017-08, Vol.129 (32), p.9568-9572
Main Authors: Dang, Thu‐Thuy T., Franke, Jakob, Tatsis, Evangelos, O'Connor, Sarah E.
Format: Article
Language:eng ; ger
Subjects:
Alkaloide
Bifurcations
Biosynthesen
Biosynthesis
Catalysis
Catalytic activity
Chemistry
Cytochrome
Cytochrome P450
Cytochrom P450
Hydroxylase
Isomerization
Perakin
Plants
Plants (botany)
Vomilenin
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Summary:Plants create tremendous chemical diversity from a single biosynthetic intermediate. In plant‐derived ajmalan alkaloid pathways, the biosynthetic intermediate vomilenine can be transformed into the anti‐arrhythmic compound ajmaline, or alternatively, can isomerize to form perakine, an alkaloid with a structurally distinct scaffold. Here we report the discovery and characterization of vinorine hydroxylase, a cytochrome P450 enzyme that hydroxylates vinorine to form vomilenine, which was found to exist as a mixture of rapidly interconverting epimers. Surprisingly, this cytochrome P450 also catalyzes the non‐oxidative isomerization of the ajmaline precursor vomilenine to perakine. This unusual dual catalytic activity of vinorine hydroxylase thereby provides a control mechanism for the bifurcation of these alkaloid pathway branches. This discovery highlights the unusual catalytic functionality that has evolved in plant pathways. Die duale katalytische Funktion eines Cytochrom P450 aus Rauwolfia serpentina leitet eine Verzweigung der Alkaloidsynthese ein. Vinorin‐Hydroxylase (VH) katalysiert die Hydroxylierung des Monoterpen‐Indolalkaloids mit anschließender nichtoxidativer Isomerisierung zur Bildung von zunächst Vomilenin und schließlich Perakin. Diese duale Aktivität erhöht die chemische Diversität und illustriert die Vielseitigkeit von Cytochrom‐P450‐Enzymen im pflanzlichen Stoffwechsel.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201705010