Subsystem- Thiamin biosynthesis.pptVIP

* Subsystem: Thiamin biosynthesis Thiamin pyrophosphate (vitamin B1) is an essential cofactor for several important enzymes of the carbohydrate metabolism. Many microorganisms, as well as plants and fungi synthesize thiamin, but it is not produced by vertebrates. Thiamin monophosphate is formed by coupling of two independently synthesized moieties, hydroxymethylthiamin-PP (HMP-PP) and hydroxyethylthiazole-P (HET-P). The HET moiety is biosynthesized in Bacillus subtilis and most other bacteria from DXP, Glycine, and cysteine in a complex oxidative condensation reaction [1]. This reaction requires five different proteins, ThiO, ThiG, ThiS, ThiF, and a cysteine desulfurase. Glycine oxidase ThiO catalyzes the oxidation of glycine to the corresponding glycine imine. Sulfur carrier protein adenylyl transferase ThiF catalyzes the adenylation of the carboxy-terminus of the sulfur carrier protein ThiS, and cysteine desulfurase catalyzes the transfer of sulfur from cysteine to the ThiS-acyl adenylate to give ThiS-thiocarboxylate. ThiG is the thiazole synthase and catalyzes formation of the thiazole from dehydroglycine, DXP, and ThiS-thiocarboxylate [2, 3, 4]. The thiazole moiety of thiamin in E. coli is derived from Tyrosine, cysteine, and DXP using another enzyme (ThiH) of yet unknown function instead of ThiO [5]. In contrast, the THI4 protein family has been shown to be involved in the thiazole synthesis in some eukaryotes [7]. The HET kinase ThiM is involved in the salvage of thiazole from the culture medium. The conversion of 5-aminoimidazole ribonucleotide (AIR) into HMP is a fascinating reaction of the thiamin biosynthetic pathway in bacteria and is probably the most complex unresolved rearrangement in primary metabolism. The thiC gene complements all HMP requiring mutants in E.coli, and B.subtilis [6]. In yeast and plants, the pyrimidine moiety of thiamin is synthesized using a distinct gene (THI5 in yeasts), and the initial substrates appear to be histi