C&EN on Vitamin B-12 Mystery

Vitamin B-12 Mystery Is Solved. ‘Enzyme structure reveals that one vitamin is cannibalized to make another. By capturing the structure of the sole missing link in its biosynthesis, scientists have solved a long-standing mystery surrounding vitamin B-12.
Vitamin B-12 is one of the largest of the known nonpolymeric natural products. Its biosynthesis is well-understood, with one notable exception: Scientists have struggled to figure out how the vitamin’s 5,6-dimethylbenzimidazole (DMB) ligand is made. Biologist Graham C. Walker of MIT, biochemist Christopher T. Walsh and crystallographer Nicholas A. Larsen of Harvard Medical School, and coworkers now have filled in that knowledge gap by solving the crystal structure of BluB, the enzyme that synthesizes DMB (Nature 2007, 446, 449).
They find that the enzyme cannibalizes one vitamin to make another. BluB forms DMB by fragmenting and contracting flavin mononucleotide, a cofactor derived from vitamin B-2. In the structure they have determined, the researchers captured an early BluB intermediate in which molecular oxygen is poised to attack the flavin.’

The Molecule of the Month: Vitamin B12



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