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MIT biologists solve vitamin puzzle

Solving a mystery that has puzzled scientists for decades, MIT and Harvard researchers have discovered the final piece of the synthesis pathway of vitamin B12-the only vitamin synthesized exclusively by microorganisms.

B12, the most chemically complex of all vitamins, is essential for human health. Four Nobel Prizes have been awarded for research related to B12, but one fragment of the molecule remained an enigma-until now.

The researchers report that a single enzyme synthesizes the fragment, and they outline a novel reaction mechanism that requires cannibalization of another vitamin.

The work, which has roots in an MIT undergraduate teaching laboratory, "completes a piece of our understanding of a process very fundamental to life," said Graham Walker, MIT professor of biology and senior author of a paper on the work that will appear in the March 22 online edition of Nature.

Vitamin B12 is produced by soil microbes that live in symbiotic relationships with plant roots. During the 1980s, an undergraduate research course taught by Walker resulted in a novel method for identifying mutant strains of a soil microbe that could not form a symbiotic relationship with a plant.

Walker's team has now found that one such mutant has a defective form of an enzyme known as BluB that leaves it unable to synthesize B12.

BluB catalyzes the formation of the B12 fragment known as DMB, 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.

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
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Source:Massachusetts Institute of Technology


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