Thiamin biosynthesis in prokaryotes

Abstract

Twelve genes involved in thiamin biosynthesis in prokaryotes have been identified and overexpressed. Of these, six are required for the thiazole biosynthesis (thiFSGH, thil, and dxs), one is involved in the pyrimidine biosynthesis (thiC), one is required for the linking of the thiazole and the pyrimidine (thiE), and four are kinase genes (thiD, thiM, thiL, and pdxK). The specific reactions catalyzed by ThiEF, Dxs, ThiDM, ThiL, and PdxK have been reconstituted in vitro and ThiS thiocarboxylate has been identified as the sulfur source. The X-ray structures of thiamin phosphate synthase and 5-hydroxyethyl-4-methylthiazole kinase have been completed. The genes coding for the thiamin transport system (thiBPQ) have also been identified. Remaining problems include the cloning and characterization of thiK (thiamin kinase) and the gene(s) involved in the regulation of thiamin biosynthesis. The specific reactions catalyzed by ThiC (pyrimidine formation), and ThiGH and ThiI (thiazole formation) have not yet been identified.

A Genetic Screen for the Identification of Thiamin Metabolic Genes

“…For clone 12, cof is most likely the gene responsible for resistance because cof is up-regulated in response to CF 3 -HMP. 2 In clones 13 and 14, either dxs or yajO could be the gene responsible for the observed antibiotic resistance. thiE is the cellular target for CF 3 -HMP, which explains the behavior of clone 15.…”

AtTHIC, a gene involved in thiamine biosynthesis in Arabidopsis thaliana

“…In E. coli, the thiazole moiety is formed from DXP (1-deoxy-D-xylulose-5-phosphate), tyrosine and cysteine [5][6][7][8][9]. Five gene products (ThiF, ThiS, ThiG, ThiH and ThiI) are involved in this step [10][11][12][13][14] (Figure 1). The pyrimidine unit is synthesized from AIR (5-aminoimidazole ribotide), and ThiC is re-quired for pyrimidine biosynthesis [14][15][16][17] (Figure 1).…”

“…Five gene products (ThiF, ThiS, ThiG, ThiH and ThiI) are involved in this step [10][11][12][13][14] (Figure 1). The pyrimidine unit is synthesized from AIR (5-aminoimidazole ribotide), and ThiC is re-quired for pyrimidine biosynthesis [14][15][16][17] (Figure 1). Subsequently, ThiE, a thiamine phosphate synthase, couples the two ring structures of pyrimidine and thiazole to form TP [9,[17][18][19][20] (Figure 1).…”

Action of the Thiamine Antagonist Bacimethrin on Thiamine Biosynthesis

“…Thiamine pyrophosphate (TPP), the biologically active cofactor, is generated by the condensation of two independently synthesized intermediates, 4-methyl-5-(␤-hydroxyethyl)thiazole (THZ) phosphate and 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) pyrophosphate. In vivo labeling studies demonstrated that the carbon atoms in HMP were derived from the purine intermediate aminoimidazole ribonucleotide (AIR), although the biochemical details of this conversion have not been elucidated (2). Mutations causing an unconditional requirement for exogenous HMP or thiamine map to a single gene, thiC.…”

“…Mutations causing an unconditional requirement for exogenous HMP or thiamine map to a single gene, thiC. In vivo labeling also determined the metabolic precursors to the THZ moiety, and several genes have been implicated in this synthesis (2,18). Our current understanding of the synthesis and salvage of TPP is presented in Fig.…”