THYME: Increasing protein production by exploiting stable protein aggregation

  • Akram, Safwan (PI)
  • Thomas, Gavin (CoI)
  • Springthorpe, Victoria (CoI)

Project: Research

Description

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.
Short titleInclusion bodies for Industrial Biotechnology (acronym: IB2)
StatusActive
Effective start/end date1/04/1931/03/20