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.
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