A selection of new scientific data has recently been published concerning the potential to improve the biomanufacturing processes of B12. The vitamin, which is crucial in maintaining, for instance, the health and function of blood cells, is missing from the vegan diet and is prohibitively expensive to buy as a supplement.
Vitamin B12 is an essential micronutrient to several functions of the human body; including playing a role in supporting red blood cell production, energy, metabolism and nerve function. It is, however, neither made, nor required by plants.
With a record 560,000 people signing up to the latest ‘Veganuary’ in 2021 and trying out an alternative diet, this important nutrient is in high demand and is made increasingly so with the recent global transition to low-meat diets, which means that biomanufacturing will need to increase in efficiency. However, due to complex molecular structure of the vitamin, it is currently not feasible to mass-produce through conventional chemical synthesis.
As a result of this, it is the only vitamin which is produced exclusively by bioproduction (this means that bacteria which naturally produce B12 are cultured as part of the manufacturing process). This process today remains inefficient and it continues to be expensive for many people who need it – particularly those living in developing nations.
New research and data by Dr Tessa Young, of the Department of Biosciences, in Durham University, UK, published in Nature Communications, explored ways and methods of understanding and improving the biosynthesis of B12 by studying the process by which enzymes obtain essential metals.
With cobalt being a crucial metal in the B12 production process, Dr Young and the Durham team worked closely with Professor Martin Warren of the University of Kent and the Quadram Institute in Norwich, whose research group engineered E. Coli strains (which don’t normally make B12) to synthesise the vitamin.
During vitamin B12 biomanufacturing, the vital element, cobalt, is supplied by a metal delivery type of enzyme. However, ensuring that this enzyme is supplying a sufficient amount of the correct metal, and so, conversely, not becoming clogged-up with the wrong one, remains an obstacle when producing B12 on a large scale and also hinders its attainability for diet supplementation.
Therefore, in order to overcome the cobalt bottleneck, Dr Young and the Durham team constructed a ‘metalation calculator’ as a means to understand and optimise cobalt supply for B12 to support the manufacture of this essential vitamin.
Dr Young commented that “by understanding the mechanism that distributes vital metals, it has become possible to produce a calculator which industrial biotechnologists can use to optimise their manufacturing reactions.
“The calculator has been tested in the production of vitamin B12 and we hope to see it adopted by biotechnology manufacturers to help foster a more sustainable future.”
Senior author Professor Nigel Robinson, also in the Department of Biosciences at Durham University, said that “about a half of life’s reactions are catalysed by metals including iron, copper, zinc, magnesium, manganese, nickel and cobalt.
“This paper describes the underlying mechanism that distributes these metals to the reaction centres inside living cells. Industrial Biotechnology manufactures compounds that society needs sustainably, by replacing processes that use fossil fuels with yeast, bacteria or the cells of other organisms as the alternative factories.”
The ability of the ‘metalation calculator’ to determine the metal requirements for producing B12 on a large scale demonstrates great potential and use for the future, not only for the manufacturing of this supplement, but also in wider sustainable manufacturing processes using biotechnology.
This Durham University research was funded by The Royal Commission for the Exhibition of 1851 and the BBSRC.
New funding from the BBSRC, which was awarded this month, will allow the calculator to be tested widely and to be developed into easy-to-use computer applications.
For information about the BBSRC-funded network assisting the exploitation of metals-in-biology discoveries in industrial biotechnology visit https://sites.durham.ac.uk/mib-nibb/.
The source for this article is taken from a press release provided by Durham University. For information and enquiries, please contact Durham University Communications Team: communications.team@durham.ac.uk.
Paper DOI: 10.1038/s41467-021-21479-8.
Featured Image: ‘Metal Solutions’ by Durham University on Dropbox.