Team:Exeter

Our aim is to design a system for the synthesis of bespoke polysaccharides in Escherichia coli. We intend to show that a future where designer polysaccharides can be created on demand is not only feasible, but in fact highly achievable.

The ability to tailor-make polysaccharides would lead to revolutionary technological developments in many fields, such as medicine (rapid vaccine production) and the industrial sector (production of novel materials) to name but two.

We are using several approaches to demonstrate how this is possible. Firstly we want to synthesise useful existing polysaccharides (such as hyaluronan) in the unfamiliar setting of E. coli. Secondly, to achieve the synthetic polysaccharide, we will implement the addition of glycosyltransferases from different E. Coli to our own sample strain, both individually for characterisation and in an operon, allowing polysaccharide production via the well documented Wzy-dependent system. As well as implementing a full operon for each polysaccharide, we plan to construct an engineered plasmid. This will allow controlled expression of different enzymes, induced through different promoters to enable choice without repeated genetic transformations..

The complementary dry lab work provides a basis for that of the wet lab and the principle of in vivo synthesis of novel polysaccharides. The generation of a database of enzymes with a user-friendly interface will aim to assist polysaccharide design, leading to a future where any polysaccharide is possible. We are also investigating kinetic models to flag up conflicts in enzyme activities to optimise polysaccharide construction pathways, and we plan to use TinkerCell to explore possible methods of controlling multiple enzyme expression and enzyme expression levels.