This project aims to apply synthetic biology and metabolic engineering strategies to one of the most complex biochemical pathways found in nature in order to address a current need for a cheaper and more reliable source of vitamin B12, the so-called anti-pernicious anaemia factor. Vitamin B12 is a cobalt-containing molecule that acts as a coenzyme and cofactor for a number of key biological processes. It is unique among the vitamins in that it is made solely by prokaryotes but is retained by many eukaryotes as a nutrient because of the greatly improved rates of reaction observed with B12-dependent enzymes in comparison to B12-independent processes. Vitamin B12 is a structurally complex molecule and this is reflected in an equally complex biochemical pathway. Our research group at QIB have worked for many years on the biochemistry of the pathway and are recognised for their many contributions to this area. BASF are pioneers in the area of commodity and speciality chemicals and are market leaders in vitamin production. This joint project between the Warren lab and BASF, therefore, presents an opportunity to provide new key fundamental insights into the operations of the B12 biosynthetic pathway and at the same time lead to the construction of a strong B12-overproduction strain.

References

Kieninger C, Deery E, Lawrence A, Podewitz M, Wurst K, Nemoto-Smith E, Widner FJ, Baker JA, Jockusch S, Kreutz CR, Liedl KR, Gruber K, Warren MJ, Kräutler B (2019) The Hydrogenobyric Acid Structure Reveals the Corrin Ligand as an Entatic State Module Empowering B12-Cofactors for Catalysis. Angew Chem Int Ed Engl. 58(31):10756-10760. doi: 10.1002/anie.201904713.

Lawrence AD, Nemoto-Smith E, Deery E, Baker JA, Schroeder S, Brown DG, Tullett JMA, Howard MJ, Brown IR, Smith AG, Boshoff HI, Barry CE, Warren MJ (2018) Construction of fluorescent analogues to follow the uptake and distribution of cobalamin (vitamin B12) in bacteria, worms and plants. Cell Chemical Biology 25, 1–11. doi.org/10.1016/j.chembiol.2018.04.012.

Moore SJ., Sowa ST., Schuchardt C., Deery E., Lawrence AD., Ramos JV., Billig S., Birkemeyer C., Chivers PT., Howard MJ., Rigby SEJ., Layer G and Warren MJ (2017) Elucidation of the biosynthesis of the methane catalyst coenzyme F430. Nature 543(7643):78-82 DOI 10.1038/nature21427

Entry Requirements

Candidates for academic admission to a doctoral degree at UEA and for entry to the NRPDTP programme must have obtained (or be about to obtain), a First or Upper Second-class UK Honours degree, or qualifications gained outside the UK that are considered to be equivalent. Applicants with a Lower Second-class degree will be considered if they also have a Master’s degree, or have significant research or non-academic experience relevant to the proposed field of research. Studentships awarded based on predicted grades will be conditional upon final results.

English Language requirement (UEA Faculty of Science equivalent: IELTS 6.5 overall, 6 in each category).

Funding

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) PhD studentship. The studentship includes payment of tuition fees (directly to the University), a stipend for each year of the studentship (2021/22 stipend rate: £15,609), and a Research Training Support Grant for each year of the studentship of £5,000 p.a.

More information on eligibility and funding can be found here.

About The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP)

The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to UK and international candidates for entry October 2021 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

This project has been shortlisted for funding by the NRPDTP programme. Shortlisted candidates can expect to be interviewed on either Tuesday 25th, Wednesday 26th or Thursday 27th January 2022. Shortlisted candidates will be notified of their interview times by email no later than 12 January 2022.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.