Partager
Ecouter
Actualité

Geissoschizine Cyclase: A Discovery Revolutionizing the Understanding and Synthesis of Pharmacologically Important Monoterpenoid Indole Alkaloids

  • Pharmacie,
  • Santé-Sciences-Technologie,
Date(s)

le 10 décembre 2024

Lieu(x)

Site Grandmont

EA2106 BBV - Biomolécules et Biotechnologies végétales

As part of the MIACYC project, a major breakthrough has been made in understanding the enzymatic mechanisms responsible for the synthesis of monoterpenoid indole alkaloids (MIAs), valuable compounds with various pharmacological applications. Through combined transcriptomic analyses of the epidermis and leaves of Alstonia scholaris, enhanced by the overexpression of the transcriptional regulator MYC2, our teams identified a key enzyme: geissoschizine cyclase.

This unique enzyme catalyzes the formation of essential C-C and C-N bonds, producing several types of alkaloids, including strictamine, known for its neuropharmacological properties but also akuammicine and 16-epi-pleiocarpamine. Our findings also reveal a shared metabolic organization between A. scholaris and Catharanthus roseus, highlighting the evolutionary conservation of MIA biosynthetic pathways.

Geissoschizine cyclase stands out for its ability to generate three distinct alkaloid structures—akuammilan, strychnos, and mavacuran—from its substrate, geissoschizine, marking a key step in understanding cyclization mechanisms. This discovery opens new perspectives for elucidating metabolic pathways and the sustainable production of MIAs through metabolic engineering, advancing the development of new therapeutic solutions.
 

You can reach our article here  :

Harnessing the spatial and transcriptional regulation of monoterpenoid indole alkaloid metabolism in Alstonia scholaris leads to the identification of broad geissoschizine cyclase activities, Plant Physiology and Biochemistry, Volume 219, 2025.109363, ISSN 0981-9428, https://doi.org/10.1016/j.plaphy.2024.109363.

Authors : Louis-Valentin Méteignier, Sarah Szwarc, Patra Barunava, Mickael Durand, Duchesse-Lacours Zamar, Caroline Birer Williams, Nicolas Gautron, Christelle Dutilleul, Konstantinos Koudounas, Enzo Lezin, Thomas Perrot, Audrey Oudin, Stéphanie Pateyron, Etienne Delannoy, Veronique Brunaud, Arnaud Lanoue, Bilal Haider Abbasi, Benoit St-Pierre, Michael Krogh Jensen, Nicolas Papon, Chao Sun, Pierre Le Pogam, Ling Yuan, Mehdi A. Beniddir, Sébastien Besseau, Vincent Courdavault

Keywords: Alstonia scholaris, Alkaloid, Epidermis-transcriptomic, MYC2, Strictamine,16-epi-pleiocarpamine,Cytochrome P450