THYME: Increasing protein production by exploiting stable protein aggregation

Increasing productivity in bio-based protein production will reduce costs and waste in this important sector of the UK bioeconomy. Working with Teesside-based Fujifilm Diosynth Biotechnologies (FDB), this project provides important proof of concept data to develop a disruptive technology leading to significantly process improvements by increasing yield and decreasing downstream processing. This new Teesside-York collaboration will exploit how microbes respond to the formation of protein aggregates (or inclusion bodies, IBs) during bioprocess conditions. IB formation has, until relatively recently, been generally avoided, despite many proteins retaining functionality as part of IBs. The usual industrial processes use IBs after solubilising them in vitro. In fact, IBs provide a route to achieve high product yields with >95% protein purity and greatly reduced downstream processing costs. IB formation is not the default expression route due to lack of understanding of what protein features drive the formation of stable aggregates, rather than directing proteins for degradation. Working within FDB’s commercial pAVEWAy® system, we will undertake bacterial fermentations producing highly similar proteins that either induce or don’t induce IB formation to understand the cellular response to their alternative fates. The data will be analysed in DETOXbase, using new tools for modelling protein production stress. The project will yield data directly relevant for FDB’s commercial pipeline & increase the functionality and commercial potential of DETOXbase.