Steve Ealick's Research Group

Abstract:

The biosynthesis of thiamin pyrophosphate in prokaryotes, as represented by the Escherichia coli and the Bacillus subtilis pathways, is summarized in the figure below. The thiazole heterocycle is formed by the convergence of three separate pathways. First, the condensation of glyceraldehydes 3-phosphate and pyruvate catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase gives 1-deoxy-D-xylulose 5-phosphate. Next, the sulfur carrier protein ThiS-COO- is converted to its carboxyterminal thiocarboxylate in reactions catalyzed by ThiF, ThiI and NifS (ThiF and IscS in B. subtilis). Finally, tyrosine (glycine in B. subtilis) is converted to dehydroglycine by ThiH (ThiO in B. subtilis). Thiazole synthase (ThiG) catalyzes the complex condensation of ThiS-COSH, dehydroglycine and DXP to give a thiazole tautomer, which is then aromatized to carboxythiazole phosphate by TenI (B.subtilis). Hydroxymethyl pyrimidine phosphate is formed by a complicated rearrangement reaction of 5-aminoimidazole ribonucleotide catalyzed by ThiC. ThiD then generates HMP-PP. Coupling of the two heterocycles and decarboxylation, catalyzed by thiamin phosphate synthase (ThiE), gives thiamin phosphate. A final phosphorylation, catalyzed by ThiL, completes the biosynthesis of thiamin pyrophosphate, the biologically active form of the cofactor.
This chapter reviews the current status of mechanistic and structural studies on the enzymes involved in this pathway.