14. August 2018, 13.15 p.m. 

Ernst-Abbe-Platz 2, seminar room 3423

Exploring the biosynthetic origin of psychoactive kavalactones in kava using high-throughput molecular approaches

Dr. Tomas Pluskal
(Whitehead Institute for Biomedical Research, Cambridge, USA)

Although plants present an incredibly rich source of pharmaceutically relevant specialized metabolites, biosynthetic pathway elucidation in plants has proven challenging. Unlike bacteria and many fungal species that contain biosynthetic operons, the genes of a given plant specialized metabolic pathway typically scatter across the genome, making pathway discovery via genome mining nearly impossible. Leveraging a diverse set of molecular tools developed for studying specialized metabolism in non-model organisms, we recently identified and characterized seven enzymes that constitute the biosynthetic pathway of kavalactones, the psychoactive principles of kava (Piper methysticum). Kava is an ethnomedicinal shrub native to the Polynesian islands with anxiolytic and analgesic properties supported by over 3,000 years of traditional use as well as numerous recent clinical trials. Kavalactones interact with human central nervous system through mechanisms distinct from those of common prescription psychiatric drugs such as benzodiazepines or opioids. We further demonstrated the feasibility of engineering heterologous production of kavalactones and their derivatives in bacterial, yeast, and plant hosts, thus opening an avenue towards the development of novel non-addictive psychiatric therapeutics through the means of synthetic biology. We aim to generalize the presented workflow into a generally applicable experimental and computational platform for exploring and exploiting the remarkable chemodiversity of non-model plant species.

References

[1] Pluskal T, Torrens-Spence MP, Fallon TR, De Abreu A, Shi CH, Weng J-K, bioRxiv 2018

[2] Li F-S, Weng J-K, Nature Plants 2017

[3] Torrens-Spence MP, Fallon TR, Weng J-K., Meth Enzymol 2016