Project

Tackling functionality and balanced expression of cytochrome P450 enzymes: a generic toolbox for the production of specialized plant metabolites in bacteria

Code
1SHF624N
Duration
01 November 2023 → 31 October 2027
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Computational biomodelling and machine learning
    • Synthetic biology
  • Engineering and technology
    • Industrial microbiology
Keywords
Transmembrane domains Inner-membrane and oxidative stress Cytochrome P450
 
Project description

The natural diversity of plant metabolites, such as flavonoids, offers a plethora of attractive attributes through the decoration of a common skeleton. Oxygenation is the most common decoration and is added in the final biochemical steps in the plant endoplasmic reticulum. Industrial production of these specialized flavonoids can be achieved chemically, through plant cell cultures or via extraction. These routes are paired with high costs and low efficiencies, limiting the economic potential. Industrial biotechnology (IB) and synthetic biology strive to circumvent such problems by producing desired metabolites in microbial hosts, referred to as microbial cell factories (MCFs). However, to present IB lacks oxygenation tools to realize the efficient oxygenation of flavonoids. With this PhD proposal, I aim to create a decoration platform for flavonoids in E. coli, the workhorse of IB. New-to-nature developed transmembrane domains will allow efficient membrane integration of the required oxygenation machinery. Relief of inner-membrane and/or oxidative stress will be realized through dynamic regulation to ensure maximal production with minimal metabolic burden. These modifications will result in improved MCFs with industrial relevance. By unlocking the oxygenation potential in MCFs, socio-economically relevant molecules with applications in pharma, cosmetics and food industries can be produced in an environmentally friendly and cost-effective manner.