Breakthrough into the construction of vitamin B12

Bioscientists at the University of Kent have revealed for the first time how vitamin B12/antipernicious anaemia factor is made. The mystery of its construction is often referred to as “the Mount Everest of biosynthetic problems” - not only does the complex vitamin involve around 30 individual components which are ‘pieced together’, but it is also only made by certain bacteria.

It was discovered in the early 1990s that two pathways exist in nature to allow for the vitamin’s construction - one that requires oxygen (aerobic) and one that occurs in the absence of oxygen (anaerobic). The more common anaerobic pathway has proved elusive to scientists because, as the researchers state, “many of its intermediates have proven technically challenging to isolate, because of their inherent instability”, as well as their rapid degradation.

But the bioscientists have managed to train the bacterium Bacillus megaterium to produce all the components of the anaerobic B12 pathway, which has thus helped them acquire the missing molecular pieces of the jigsaw and complete the picture of how the molecule is made. Their research has since been published in the journal PNAS.

With this information, the team hopes the bacteria can be persuaded to make the vitamin in larger quantities, thereby contributing to its use in medication for people suffering with the blood disorder pernicious anaemia. Research leader Professor Martin Warren added that their knowledge could be “applied with the emerging discipline of synthetic biology to produce strains of bacteria that make enough B12, and other vitamins, for use in medicine and other sectors, such as feed for livestock”.

Key academic partners in the research included Dr Rebekka Biedendieck (Braunschweig University of Technology) and Dr Steve Rigby (Manchester Institute of Biotechnology). The Kent team also included Dr Simon Moore and Dr Mark Howard, Reader in Biological NMR Spectroscopy. The research was funded by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC) to Professor Warren and Dr Howard.

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