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Review
. 2009:78:569-603.
doi: 10.1146/annurev.biochem.78.072407.102340.

The structural and biochemical foundations of thiamin biosynthesis

Christopher T Jurgenson  1 , Tadhg P Begley, Steven E Ealick
Affiliations
Review

The structural and biochemical foundations of thiamin biosynthesis

Christopher T Jurgenson et al. Annu Rev Biochem. 2009.

Abstract

Thiamin is synthesized by most prokaryotes and by eukaryotes such as yeast and plants. In all cases, the thiazole and pyrimidine moieties are synthesized in separate branches of the pathway and coupled to form thiamin phosphate. A final phosphorylation gives thiamin pyrophosphate, the active form of the cofactor. Over the past decade or so, biochemical and structural studies have elucidated most of the details of the thiamin biosynthetic pathway in bacteria. Formation of the thiazole requires six gene products, and formation of the pyrimidine requires two. In contrast, details of the thiamin biosynthetic pathway in yeast are only just beginning to emerge. Only one gene product is required for the biosynthesis of the thiazole and one for the biosynthesis of the pyrimidine. Thiamin can also be transported into the cell and can be salvaged through several routes. In addition, two thiamin degrading enzymes have been characterized, one of which is linked to a novel salvage pathway.

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Figures

Figure 1
Figure 1
Complete de novo thiamin biosynthetic pathway in bacteria.
Figure 2
Figure 2
(a) The 1-deoxy-D-xylulose 5-phosphate synthase (Dxs) crystal structure. (b) Active-site residues. (c) The reaction mechanism for Dxs.
Figure 3
Figure 3
(a) Crystal structure of the ThiF-ThiS complex. (b) Modeled structure of ATP in the ThiF active site.
Figure 4
Figure 4
(a) Crystal structure of ThiI. (b) Active-site residues that interact with bound AMP.
Figure 5
Figure 5
(a) X-ray structure of glycine oxidase, ThiO. (b) Active-site residues that interact with N-acetylglycine (NAG) and the isoalloxizine ring of flavin adenine dinucleotide (FAD).
Figure 6
Figure 6
(a) X-ray structure of the ThiG-ThiS complex. (b) The reaction mechanism of ThiG.
Figure 7
Figure 7
(a) X-ray structure of TenI. (b) Active-site residues interacting with thiazole carboxylate phosphate (TCP). (c) The proposed reaction mechanism of TenI
Figure 8
Figure 8
(a) X-ray structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase, ThiC. (b) Active-site model showing residues interacting with desamino AIR (IMR), S-adenosylmethionine (SAM), and the Fe4S4 cluster. (c) The origin of the atoms of HMP-P derived from isotopic labeling studies.
Figure 9
Figure 9
(a) X-ray structure of ThiD. (b) Active-site residues interacting with HMP.
Figure 10
Figure 10
(a) X-ray structure of thiamin phosphate synthase, ThiE. (b) Active-site residues interacting with thiazole phosphate (THZ-P), HMP, and pyrophosphate (PPi).
Figure 11
Figure 11
(a) X-ray structure of ThiL. (b) Stereoview of the active site of ThiL with bound thiamin monophosphate (TMP) and ATP analog AMP-PCP
Figure 12
Figure 12
(a) Thiaminase I crystal structure. (b) Active-site residues with the inhibitor 4-amino-2,5-dimethylpyrimidine (ADP). (c) The reaction mechanism for thiaminase I.
Figure 13
Figure 13
(a) X-ray structure of TenA. (b) Stereoview of the active site of TenA with 4-amino-5-hydroxymethyl-2-methylpyrimidme (HMP) bound.
Figure 14
Figure 14
Salvage pathways for thiazole, thiamin, and pyrimidine.
Figure 15
Figure 15
(a) X-ray structure of thiazole kinase (ThiM). (b) Active site of ThiM with thiazole phosphate (THZ-P) and ATP bound.
Figure 16
Figure 16
(a) Thiamin pyrophosphokinase (THI80) crystal structure. (b) Active-site residues shown with their chain identifications.
Figure 17
Figure 17
(a) X-ray structure of the thiamin-binding protein TbpA. (b) Thiamin-binding residues are shown with bound thiamin phosphate (TP).
Figure 18
Figure 18
(a) X-ray structure of the YkoF dimer. (b) High-affinity binding site for thiamin alcohol (ThOH). (c) Low-affinity binding site for thiamin alcohol.
Figure 19
Figure 19
(a) X-ray structure of the THI-box. (b) Stereoview of the ThDP-binding site of the THI-box.
Figure 20
Figure 20
Thiamin biosynthetic pathway in yeast.
Figure 21
Figure 21
(a) X-ray structure of the Thi4 octamer. (b) Active-site residues that bind adenylated thiazole (ADT). (c) Overall Thi4 reaction with carbon atoms from NAD common to ADT colored red. (d) The mechanism of Thi4.
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