Peroxisome compartmentalisation of capsaicinoid biosynthesis in yeast

Capsacinoids is a pharmaceutically important group of plant natural products that have been suggested to be used for treatment of various pathological conditions, including disorders associated with the peripheral and central nervous system.

They are potent agonists of certain TRP ion channels, which are responsible for detection of noxious stimuli and activation of nociceptors.

Identification of novel drugs that modulate the activity of TRP ion channels and does not give adverse side-effects are highly desirable.In this project we will explore the potential of metabolic engineering of the yeast peroxisome for efficient production of new-to-nature capsaicinoids with potentially beneficial bioactivities.

Like many other alkaloids, they are cytotoxic and inhibit production and reduce stability of the cultures.

To solve this issue, we propose to repurpose the peroxisome to a toxic compartment, which mimics membrane-enclosed vesicles found in the chili pepper plant.

Peroxisome compartmentalisation can reduce fitness burden of capsaicinoids, as well as to supply important metabolites via the beta-oxidation pathway.

We will evaluate beta-oxidation pathways from different species for their ability to produce branched-chain and medium-chain acyl-CoA:s, the precursors of capsaicinoids.

We will also answer the fundamental question to what extent the peroxisome can retain and accumulate capsaicinoids as model for alkaloids, and whether this provides stability of production cultures.