Funding
Funded
Closing date
Closed
This project is now closed. The details below are for information purposes only. View our current projects here.
The Centre for Enzyme Innovation is proud to be able to offer two new PhD opportunities through the SoCoBio Doctoral Training Programme (DTP).
Each DTP studentship encompasses a broad, 4-year research training programme which provides students with the skills they need to develop into future bioscience leaders in academia or in industry.
Please note, all applications must be made via the SoCoBio website only.
Apply now at the SoCoBio website
Production of chemicals and fuels by creating new linear paths for efficient bacterial assimilation of CO2 and formate
Primary Supervisor
Professor John McGeehan (University of Portsmouth)
Co-Supervisor(s)
Professor Martin Warren (University of Kent), Dr Michael Zahn (University of Portsmouth) Professor Andy Pickford (University of Portsmouth)
View the project at the South Coast Biosciences Doctoral Training Partnership website
The production of fuels and commodities as well as fine chemicals by bacterial C1-assimilation (CO2-valorization) will compete with lignin valorization and plastics upcycling in a future circular carbon economy.
The aim of this work is to establish efficient formatotrophic and autotrophic growth in methylotrophic bacteria and E.coli by integrating new linear C1-assimilation pathways thereby replacing multi-step ATP-consuming cyclic pathways.
The key enzyme will be a thiamine-dependent Lyase from Actinomycetospora chiangmaiensis, which was recently described by our German collaborator Dr. Thore Rohwerder at the Helmholtz Centre for Environmental Research in Leipzig (1).
This enzyme is able to condense formyl-CoA with acetone and other short-chain carbonyl compounds to the corresponding 2-Hydroxyacyl-CoA thioesters. Research at the Centre for Enzyme Innovation (CEI) in Portsmouth utilises enzyme purification, structure determination by X-ray crystallography, and biophysical characterisation.
This PhD studentship at the University of Portsmouth will focus on the structure-guided engineering of the Lyase reaction towards the production of glycolyl-CoA and glyoxyl-CoA by condensing formyl-CoA with formaldehyde and formate, respectively. Further carboligation of two glyoxylate molecules to tartronate semialdehyde by glyoxylate carboligase and the subsequent reduction and phosphorylation to 3-phosphoglycerate would directly contribute to gluconeogenesis (2).
The starting material formate can be produced by electrochemical reduction of carbon dioxide or by formate dehydrogenases whereas formyl-CoA can be formed either by a CoA-ligase or a CoA-transferase.
For the South Coast Biosciences Doctoral Training Partnership we will start a new collaboration with Prof. Martin Warren from the University of Kent. The toxicity of formate and formaldehyde is a major problem in bacterial cells and bacterial microcompartments (BMCs) represent a way of performing all the C1-assimilation steps including the Lyase reaction in a shielded environment.
Prof. Martin Warren has excellent expertise in the formation and handling of BMCs and in the bioengineering of metabolic pathways. He will be the second supervisor of this project.
Application deadline:
Monday 4 January 2021 (midnight GMT)