The mystery of vitamin B12 finally solved

The mystery of vitamin B12 finally solved

Summary: You probably think that scientists know everything about the common and essential vitamin B12, the only vitamin synthesized by soil microbes. In fact, one part of this biosynthesis has puzzled researchers for at least 50 years. But now, MIT and Harvard biologists have solved this vitamin puzzle by discovering that a single enzyme known as BluB synthesizes the vitamin. So what is the next challenge for the researchers? It's to discover why the soil microorganisms synthesize the vitamin B12 at all, because neither them -- nor the plants they're attached to -- need it to live.

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You probably think that scientists know everything about the common and essential vitamin B12, the only vitamin synthesized by soil microbes. In fact, one part of this biosynthesis has puzzled researchers for at least 50 years. But now, MIT and Harvard biologists have solved this vitamin puzzle by discovering that a single enzyme known as BluB synthesizes the vitamin. So what is the next challenge for the researchers? It's to discover why the soil microorganisms synthesize the vitamin B12 at all, because neither them -- nor the plants they're attached to -- need it to live.

This work "completes a piece of our understanding of a process very fundamental to life," said Graham Walker, MIT professor of biology, who led the research about the catalyzing effects of the BluB enzyme.

BluB catalyzes the formation of the B12 fragment known as DMB [dimethylbenzimidazole for the curious,] which joins with another fragment, produced by a separate pathway, to form the vitamin. One of several possible reasons why it took so long to identify BluB is that some bacteria lacking the enzyme can form DMB through an alternate pathway, Walker said.

Below is a "cross-section of BluB's molecular surface. The two-fold axis lies along the y axis such that the si-face of FMN is viewed on the left and re-face on the right. The surface is coloured according to electrostatic potential, where blue is electropositive, red is electronegative and kB is Boltzmann's constant." (Credit: Graham Walker laboratory, via Nature) Here are two links to a larger version of this picture and to other figures and tables.

BluB's molecular surface

It's really interesting to note that the vitamin B12 biosynthesis involves the unusual "cannibalization" of vitamin B2.

One of the most unusual aspects of BluB-catalyzed synthesis is its cannibalization of a cofactor derived from another vitamin, B2. During the reaction, the B2 cofactor is split into more than two fragments, one of which becomes DMB. Normally, the B2-derived cofactor would assist in a reaction by temporarily holding electrons and then giving them away. Such cofactors are not consumed in the reaction. Cannibalization of a cofactor has very rarely been observed before in vitamin synthesis or any type of biosynthetic pathway, says Michiko Taga, an MIT postdoctoral fellow in Walker's lab [and already co-author of 113 scientific papers according to PubMed.]

This work has been reported by Nature under the name "BluB cannibalizes flavin to form the lower ligand of vitamin B12" (Volume 446, Number 7134, Pages 449-453, March 22, 2007). Here are two links to the abstract and to the editor's summary, "The long road to vitamin B12."

So now that the biologists know how the vitamin B12 is synthesized, what will be their next research step? "Still to be explored is the question of why soil bacteria synthesize B12 at all, Walker said. Soil microorganisms don't require B12 to survive, and the plants they attach themselves to don't need it either, so he speculates that synthesizing B12 may enable the bacteria to withstand 'challenges' made by the plants during the formation of the symbiotic relationship."

Sources: Anne Trafton, MIT News Office, March 21, 2007; and various websites

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