Figure 1 - full size

 

Figure 1.
(a) Overall bacterial pathway. AIR (12) is converted to HMP-P (15) by HMP-P synthase (ThiC), which is phosphorylated by ThiD to give HMP pyrophosphate (3). The thiazole moiety (2) is biosynthesized from DXP (6), cysteine (8) and dehydroglycine (34). The dehydroglycine is generated from glycine (ThiO) in B. subtilis and from tyrosine (ThiH) in E. coli. The pyrimidine and thiazole are coupled by ThiE to give thiamine phosphate (4), and ThiL catalyzes the final phosphorylation. (b) Conversion of AIR to the thiamine pyrimidine in bacteria and plants. The color coding indicates the source of nonhydrogen atoms in HMP-P as demonstrated by labeling studies. (c) Biosynthesis of thiamine pyrimidine in fungi. In fungi the pyrimidine moiety is derived from histidine (13) and pyridoxal 5'-phosphate (14) using a single enzyme, THI5p. The color coding indicates the source of nonhydrogen atoms. (d) The HMP-P synthase reactions. When iron-sulfur cluster–loaded HMP-P synthase is reduced with dithionite, it reduces SAM (16) to generate methionine (28) and the 5'-deoxyadenosyl (5-dAdo) radical (17), which is required by HMP-P synthase to convert AIR to HMP-P.

The above figure is reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nat Chem Biol (2008, 4, 758-765) copyright 2008.