Molecular basis of the biosynthesis of pharmacologically active alkaloids from Carolina Jasmine

• Applicant: Professor Dr. Jakob Franke
• Subject Area: Plant Biochemistry and Biophysics ; Biological and Biomimetic Chemistry
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286056487

• Final Report Year: 2018

Final Report Abstract

Alkaloids are plant products well known for their potent biological activities, many of which have been or are still used as medicine. Unfortunately, many alkaloid-producing plants are rare, grow slowly and produce only small amounts of valuable components. A better understanding of how plants make these drugs is key to improve their production by biotechnological means. The aim of the project was to gain insights into the molecular basis of alkaloid production in Carolina Jasmine (Gelsemium sempervirens). Building on modern genome and transcriptome sequencing techniques, it was possible to quickly identify eight genes involved in the biochemical pathway of Gelsemium alkaloids. Even more, techniques and findings from this project were transferred to related pathways in Indian snakeroot (Rauwolfia serpentina) and Madagascar periwinkle (Catharanthus roseus), resulting in the discovery of key enzymes for the production of the clinically used alkaloids ajmaline, vincristine and vinblastine. These results will help to establish a better and cheaper supply with these drugs in the future.

Publications

• A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate. Nat. Commun. 2017, 8, 316
  Tatsis, Evangelos C.; Carqueijeiro, Inês; Dugé de Bernonville, Thomas; Franke, Jakob; Dang, Thu-Thuy T.; Oudin, Audrey; Lanoue, Arnaud; Lafontaine, Florent; Stavrinides, Anna K.; Clastre, Marc; Courdavault, Vincent & O’Connor, Sarah E.
  
• Dual Catalytic Activity of a Cytochrome P450 Controls Bifurcation at a Metabolic Branch Point of Alkaloid Biosynthesis in Rauwolfia serpentina. Angew. Chem. Int. Ed. 2017, 56, 9440–9444
  Dang, Thu‐Thuy T.; Franke, Jakob; Tatsis, Evangelos & O'Connor, Sarah E.
  
• (2018). Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization modes. Nature chemical biology, 14(8), 760-763
  Dang, Thu-Thuy T.; Franke, Jakob; Carqueijeiro, Ines Soares Teto; Langley, Chloe; Courdavault, Vincent & O’Connor, Sarah E.