Commercialisation of the Tat protein export pathway for biopharmaceutical production
Lead Research Organisation:
University of Kent
Department Name: Sch of Biosciences
Abstract
Over 30% of licensed therapeutic proteins are made in the bacterium Escherichia coli, where 'export' out of the cytoplasm to the periplasm is a favoured strategy. Current export strategies have severe limitations and we have shown that the 'Tat' export pathway has a number of advantages over traditional systems. The research will enable us to fully commercialise a suite of powerful Tat-based platforms:
1. We will optimise a previously-described system in which expression of a Bacillus subtilis Tat system in an E. coli tat deletion strain leads to export to the periplasm and then release to the medium. We will calibrate the leaky outer membrane phenotype to achieve the optimal balance of cell robustness vs membrane leakiness.
2. We will commercialise a new platform in which biotherapeutics are exported by Tat with disulphide-bonds subsequently formed in the periplasm.
3. We will identify new Tat-based systems that operate more efficiently than the E. coli system.
1. We will optimise a previously-described system in which expression of a Bacillus subtilis Tat system in an E. coli tat deletion strain leads to export to the periplasm and then release to the medium. We will calibrate the leaky outer membrane phenotype to achieve the optimal balance of cell robustness vs membrane leakiness.
2. We will commercialise a new platform in which biotherapeutics are exported by Tat with disulphide-bonds subsequently formed in the periplasm.
3. We will identify new Tat-based systems that operate more efficiently than the E. coli system.
Organisations
People |
ORCID iD |
| Colin Robinson (Principal Investigator) |
| Description | We use the Tat protein export system to export high-value proteins to the periplasm in a folded state in E. coli. One aim of this grant is to use Tat systems from different bacteria in place of E. coli's native system. This is because the E. coli system works well, but is relatively slow in transporting proteins. We have now shown that some heterologous Tat systems have excellent potential for exporting biotherapeutics at high rates and we are preparing to patent some of these discoveries. |
| Exploitation Route | The aim is to commercialise these findin=gs together with a series of industrial collaborators |
| Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |
| Title | New E. coli strains |
| Description | We have developed new strains of E. coli that export proteins to the periplasm by a novel pathway |
| Type Of Material | Cell line |
| Year Produced | 2010 |
| Provided To Others? | Yes |
| Impact | Several groups are testing these strains with a view to using them for production production on analytical or production scale |
| Description | Open day presentations |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Hosted open day visits to my lab in majority of UCAS days - 2 groups of UCAS applicants + parents per open day, at least 10 open days per year Increased understanding of biotech projects at Kent |
| Year(s) Of Engagement Activity | 2007,2009,2011,2012,2013,2014,2015,2016 |