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Biosciences Funded PhD - Towards a recombinant cobalamin (vitamin B12) production strain.

The studentship will pay an
annual stipend at the UK Research Council rate of £14,553 (rate for 2017/2018)
and cover tuition fees at the rate for UK/ EU students. International
applicants must make provision to meet the difference between Home and
International fees.

Towards a recombinant
cobalamin (vitamin B12) production strain

Martin Warren and Dr Evelyne Deery (Kent)

Vitamin B12 is an
important nutrient whose deficiency is associated with megaloblastic anaemia,
neurological symptoms, methylmalonic aciduria, brain atrophy and neural tube
defects in unborn babies. However, vitamin B12 is an expensive nutrient and has
to be produced from bacterial cultures grown on a large scale. We have
pioneered the construction of a recombinant E. coli strain that produces a
large amount of B12 and we now want to improve on this system using modern
synthetic biology (SynBio) approaches, utilising design algorithms to build and
optimize the B12 pathway to allow for enhanced enzyme production and maximal metabolic
flux. We have outlined methods that will allow for the construction of an
enhanced pathway for B12 synthesis and have also integrated control circuits to
make the engineered bacteria more responsive. Furthermore, we have highlighted
ways in which cobalamin analogues can be made using similar engineering

The idea behind this
project is to recombinantly produce vitamin B12 using high producing strains
capable of yields in excess of 500 mg/L. In so doing this will lead to a
reduction in production costs, secure supply, cater for an expanding vitamin
and nutraceutical market and develop B12 variants that can be used for other
medical purposes. The commercial development of the project will involve the
engineering and patenting of a number of recombinant B12 producing-strains that
can then be licensed to end-user for manufacture. Specifically, the aims of the
technical aspects of the research will involve the following:

1. The design and incorporation of a specific suite of aerobic B12 biosynthetic
genes to allow for optimal metabolic flux through the pathway using synthetic
biology approaches. These genes will be integrated into the E. coli genome
using CRISPR/Cas9 technology.

2. The use of a range of constitutive and inducible promoters will be
investigated to see if these provide more long term production of B12 during

3. Control circuits will be introduced through gene editing to reduce heme
synthesis and enhance the production of 5-aminolevulinic acid, the starting
material for all tetrapyrrole synthesis


The successful candidate is
expected to be a highly motivated student. He/she will be expected to have a
minimum of an upper 2nd class degree in an appropriate field.

How to apply

Applications can be made using the online University application page where the project title should be entered as the
proposed area of research and Prof Martin Warren as supervisor. Please include
a CV and a cover letter.

Informal enquiries can be addressed to Prof Martin Warren (m.j.warren@kent.ac.uk)


The deadline for applications has passed.

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