Pernicious problem: B12 stacks up

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  • Published: Sep 1, 2013
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Pernicious problem: B12 stacks up

First, blood

Vitamin B12, also known as the antipernicious anaemia factor is an essential nutrient for humans. Now, British scientists have pinned down the mechanism and route of its biosynthesis using electron paramagnetic resonance EPR), nuclear magnetic resonance (NMR) spectroscopy and other techniques.

Vitamin B12, also known as the antipernicious anaemia factor is an essential nutrient for humans. Now, British scientists have pinned down the mechanism and route of its biosynthesis using electron paramagnetic resonance EPR) and other techniques in what has often been referred to as the "Mount Everest of biosynthetic problems".

Vitamin B12, cobalamin, is a water-soluble vitamin related in structure to the haem group at the heart of haemoglobin. It plays a critical role in the normal functioning of the brain and nervous system, and in the production of red blood cells and as such a deficiency can lead to pernicious anaemia. Only bacteria and archaea have the necessary enzymes for its biosynthesis and as such we must obtain all we need from our diet. It can be obtained from animal foods, including fish and shellfish, meat, liver, poultry, eggs and dairy and various fermented products, including certain types of tea. And, of course, from B12 vitamin supplements. The molecule' structure was determined crystallographically by Dorothy Crowfoot Hodgkin and her team in 1956.

The path is clear

Since then, scientists have puzzled over exactly how the complex structure of cobalamin is constructed by those microbes with natural biosynthetic machinery to do so. While some have referred to the problem as a Mount Everest others see it as a chemical jigsaw puzzle of a mere 30 pieces but representing a complex picture. In the early 1990s researchers suggested that there were two pathways that allow its construction. One route is an aerobic, oxygen-dependent approach, the second is an anaerobic pathway. The latter is more common but the intermediates proved so unstable, degrading rapidly before they could be analysed and so demarcating the precise mechanism was not possible.

Now, writing in the Proceedings of the National Academy of Sciences (USA), bioscientists at the University of Kent, England, have engineered the microbe Bacillus megaterium to synthesise the individual components of the anaerobic B12 pathway. With those pieces of the puzzle isolated, the team were then able to figure out how they are pieced together at each stage of the biosynthesis.

A question of scale

Knowledge of a chemical or biochemical synthesis can lead to a way to make the end product in the laboratory and then potentially scale it up to a viable commercial production. The researchers hope that their latest discovery of the B12 anaerobic pathway will allow bacteria to be engineered to produce the vitamin or its analogues in larger quantities for use in treating pernicious anaemia and other applications. The finding also adds to our knowledge of one of life's most intriguing and enigmatic molecules.

"This is a really exciting time in the biological sciences - one where our knowledge can 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," says research leader Martin Warren who worked with Simon Moore and biological NMR specialist Mark Howard, and Rebekka Biedendieck of Braunschweig University of Technology, Germany and Stephen Rigby of Manchester Institute of Biotechnology, UK.

"Our next step is to try and over-produce the vitamin in bacteria and find easier ways to extract it from the growth medium," Warren told SpectroscopyNOW. "Ultimately we want to be able to make the vitamin in large quantities but also to be able to change the pathway so that we can make analogues that could be used to kill certain bacteria and diseased cells."

Related Links

Proc Natl Acad Sci (USA) 2013, online: "Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12)"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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