The international study, led by researchers at the University of Kent, UK, manipulated bacteria to produce all of the components needed for the anaerobic production of vitamin B12 - so helping them to complete the puzzle of exactly how the vitamin is produced.
Writing in PNAS, the team suggest that their findings could now be used to generate bacterial strains to produce the vitamin in larger quantities.
"By determining a function for all of the pathway enzymes, we complete the tool set for cobalamin biosynthesis and pave the way for not only enhancing cobalamin production, but also design of cobalamin derivatives through their combinatorial use and modification," wrote the researchers - led by Professor Martin Warren.
"This is a really exciting time in the biological sciences," added Warren. "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."
Warren and his team noted that it is well known two pathways exist in nature for the de novo biosynthesis of the coenzyme form of vitamin B12 – one aerobic and one anaerobic route.
While the aerobic pathway is well understood, the team said that the anaerobic route “has remained enigmatic because many of its intermediates have proven technically challenging to isolate, because of their inherent instability.”
But now, by studying the anaerobic cobalamin biosynthetic pathway in Bacillus megateriumthe international research team have for the first time been able to isolate all of the intermediates between uroporphyrinogen III and cobyrinic acid.
“Consequently, it has been possible to detail the activities of purified cobinamide biosynthesis (Cbi) proteins CbiF, CbiG, CbiD, CbiJ, CbiET, and CbiC, as well as show the direct in vitro conversion of 5-aminolevulinic acid into cobyrinic acid using a mixture of 14 purified enzymes,” wrote the team.
“This approach has resulted in the isolation of the long sought intermediates, cobalt-precorrin-6A and -6B and cobalt-precorrin-8.”
Published online ahead of print, doi: 10.1073/pnas.1308098110
'Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12)'
Authors: Simon J. Moore,Andrew D. Lawrence, Rebekka Biedendieck, et al