||2:00pm Mar 09, 2020
Whitehead Institute for Biomedical Research, USA
Elucidation of the biosynthetic pathway of psychoactive kavalactones in kava using de novo transcriptomics and metabolomics
Although plants are 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 typically scatter randomly 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. I will demonstrate the feasibility of engineering heterologous production of kavalactones and their novel derivatives in yeast, thus opening an avenue towards the development of novel psychiatric therapeutics. In the second part of my talk, I will introduce recent developments in the MZmine software framework for mass spectrometry data processing in metabolomics. This popular data analysis platform has gained a great momentum with the introduction of new modules for metabolite identification and molecular networking.