A “Radical Dance” in Thiamin Biosynthesis: Mechanistic Analysis of the Bacterial Hydroxymethylpyrimidine Phosphate Synthase

Tricky things with ThiC: Hydroxymethylpyrimidine phosphate (HMP-P) synthase (ThiC) catalyzes one of the most complex rearrangement reactions in primary metabolism. Deuteration experiments show that under reducing conditions, in the presence of aminoimidazole ribonucleotide, the 5′-deoxyadenosyl radical generated at the active site of ThiC reacts directly with the substrate and performs two iterative hydrogen atom abstraction events to catalyze this rearrangement (see scheme; SAM=S-adenosylmethionine).