Clue to thiamin assembly

Identification of an unusual metabolite bound to a protein implicated in thiamin biosynthesis has provided a key clue about how eukaryotes make this essential vitamin (J. Am. Chem. Soc., published online May 11, dx.doi.org/10.1021/ja061413o). Thiamin (shown) is stitched together from preassembled thiazole (red) and pyrimidine moieties. A team led by Steven E. Ealick and Tadhg P. Begley of Cornell University has now used a combination of NMR and mass spectrometry and crystallography to provide a more detailed picture of how the thiazole is put together. The researchers identified and characterized a metabolite tightly bound in the active site of the yeast enzyme thiazole synthase. The metabolite's structure-a surprising adenylated version of the thiazole-suggests that thiazole is derived from nicotinamide adenine dinucleotide, which typically functions as a redox cofactor rather than a biosynthetic starting material.