Out of Thin Air

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Science  21 Nov 2008:
Vol. 322, Issue 5905, pp. 1164
DOI: 10.1126/science.322.5905.1164b

In the pre-iPod era, eating a bowl of cold cereal at breakfast offered the opportunity for a detailed reading of the cereal box, on which the uncommon words niacin, thiamin, and riboflavin appeared. Years later, much more reading had explained the role of these trace supplements as coenzymes, needed to forestall the exotic diseases of beriberi and pellagra. Thiamin, also known as vitamin B1, is an invaluable aid in carbohydrate metabolism, specifically during chemical transformations of α-keto compounds. It contains two heterocyclic rings, a thiazole and a pyrimidine; the biosynthesis of the former is well understood; not so for the latter.

Chatterjee et al. establish by means of biochemical and structural analyses that the Caulobacter crescentus enzyme ThiC catalyzes the conversion of 5-aminoimidazole ribonucleotide (AIR) into 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P), which is then coupled to the thiazole moiety to give thiamine monophosphate. What makes this reaction more than another bit of esoterica is the intricate rearrangement of AIR atoms effected by ThiC. Of the five carbon atoms in the ribose portion of AIR, C2′ (red) is used to methylate C2 (blue) of the imidazole ring, and C4′ (pink), with C5′ still attached, is inserted in between C4 (olive) and C5 (yellow) of the imidazole ring, expanding it into a pyrimidine. How this is accomplished is not entirely clear, but these authors, as Martinez-Gomez and Downs have achieved recently for Salmonella enterica ThiC, show via in vitro reconstitution that a bound [4Fe-4S] cluster and the co-substrate S-adenosylmethionine participate in what bears the hallmarks of a radical-based mechanism. — GJC

Nat. Chem. Biol. 4, 10.1038/nchembio.121 (2008); Biochemistry 47, 9054 (2008).

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