Neutron scattering and selective deuteration for elucidating how lipids regulate metabolon formation

About the project

Most pharmaceutical compounds, colours and flavours are isolated from plants today. These valuable compounds are biosynthesised by a series of enzyme complexes that work in a concerted action. The assembly of such enzyme complexes also called metabolons, facilitates the direct transfer of the substrate between sequential enzymes, thereby, enhancing substrate channelling and preventing leakage of toxic or labile intermediates and metabolic cross-talk.

Organic synthesis in the lab is sometimes not possible or too expensive

Extracting pure products from plats constitutes a great industrial and societal challenge since they exist in low amounts and as a part of complex mixtures of other potentially toxic compounds. Organic synthesis in the lab is sometimes not possible or too expensive, therefore the bioengineering of moss and microorganism to express biosynthetic pathways for large-scale production of such compounds has been proposed lately. Since little knowledge exists on the conditions required for metabiolon assembly and disassembly, there is a risk of the release of undesired intermediates due to imperfect enzymatic channelling.

How plants guide the assembly of multi-enzyme complexes

Here, we will dissect the mechanisms by which plants guide the assembly of multi-enzyme complexes. We will use synthetic biology and neutron scattering to map the lipid-protein interactions that control the formation of thedhurrin metabolon, as a model system. This will enable rational enzyme design for improving the organization and stability of metabolons in heterologous hosts to boost the production of bioactive compounds.