During millions of years of evolution, land plants have created an astonishing variety of bioactive specialized metabolites (also referred to as ‘secondary metabolites’ or ‘natural products’) to support their defense and ecological adaptation. Such molecules often interact with human molecular receptors, thus providing an essential source of chemical scaffolds for the development of new medicines. About 25% of prescription drugs currently in use originated from plants.
The structural and stereochemical complexity of plant metabolites often renders their chemical synthesis unfeasible, but recent progress in sequencing and metabolomics technologies has opened a new avenue towards heterologous production of plant metabolites using their native biosynthetic enzymes. However, the discovery and engineering of metabolic pathways from plants remains very difficult. Our lab combinines novel computational (e.g., machine learning) and experimental approaches to develop rapid, generally applicable workflows for the discovery and utilization of bioactive molecules derived from plants.
On the right are examples of specific molecules that we are interested in. Kavalactones from kava are well known for their anti-anxiety effects. We have recently elucidated their biosynthetic network and are currently developing new types of kavalactones using metabolic engineering (see video below). Resiniferatoxin is the most potent activator of the human pain receptor TRPV1 and is under development as a new type of analgesic for severe pain. Aconitine is a sodium channel toxin that is used in China as an analgesic and a blood coagulant. Due to its intricate interlocking hexacyclic ring system and the elaborate collection of oxygenated functional groups, aconitine presents a rare example of a small molecule that no chemist has ever been able to synthesize.