Vitamin B12, or cobalamin, is one of the most complex small molecules made in nature, and requires around enzyme-mediated steps for its complete de novo construction. It is unique among all the vitamins in that its synthesis is restricted to only certain members of the prokaryotic world, its metabolic regime never appearing to transition into the eukaryotic world. Humans have to acquire the nutrient from their diet, where it is found mainly in meat and dairy products. Significantly, cobalamin is not utilised by plants and thus people on vegetarian and more specifically vegan diets are prone to deficiency – and with a trend to more sustainable crop-based diets the frequency of B12 deficiency is likely to increase. The nutrient is also the most expensive of the vitamins, with commercial providers charging up to £20K per kg, so the nutrient counts as a high value commodity. My research has focussed on ways to produce vitamin B12 more cheaply and sustainably, and also to incorporate the nutrient into plants. Previously, we have completed the elucidation of both the aerobic and anaerobic biosynthetic routes for cobalamin biosynthesis and in so doing have generated molecular detail on the mechanisms of many of the enzymes involved, thereby providing new insights into the chemical logic underpinning them. In this talk I will highlight how we have used this knowledge to engineer the pathway into E. coli and developed ways to ensure the efficient incorporation of cobalt into the nutrient. This strategy also allows us to make a range of anti-vitamin B12 molecules which act as strong inhibitors of many B12-dependent bacteria.
Martin Warren is Chief Scientific Officer at the Quadram Institute with responsibility for the development of the Institute’s scientific strategy and scientific leadership. His research interests are in the area of micronutrition with a specific focus on vitamin B12. Current projects include ways to improve diagnostics associated with deficiency, enhancement of the nutrient in plants and the development of antivitamins.
