Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction

The conversion of 5-aminoimidazole ribonucleotide (AIR) into 4-amino-2-methyl-5-hydroxymethylpyrimidine (HMP) is a fascinating reaction on the thiamin biosynthetic pathway in bacteria and is probably the most complex unresolved rearrangement in primary metabolism. We have successfully reconstituted...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2004-09, Vol.2 (17), p.2538-2546
Main Authors: Lawhorn, Brian G, Mehl, Ryan A, Begley, Tadhg P
Format: Article
Language:English
Subjects:
Cell-Free System - chemistry
Mass Spectrometry - methods
Molecular Conformation
Pyrimidines - biosynthesis
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Ribonucleotides - chemical synthesis
Ribonucleotides - chemistry
Ribonucleotides - metabolism
Saccharomyces cerevisiae - metabolism
Thiamine - biosynthesis
Thiamine - chemistry
Time Factors
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Summary:The conversion of 5-aminoimidazole ribonucleotide (AIR) into 4-amino-2-methyl-5-hydroxymethylpyrimidine (HMP) is a fascinating reaction on the thiamin biosynthetic pathway in bacteria and is probably the most complex unresolved rearrangement in primary metabolism. We have successfully reconstituted this reaction in a cell-free system. The E. coli thiC gene product and an additional unidentified E. coli protein are required for the reaction. In addition, SAM and nicotinamide cofactors are required for full activity. Labeling studies to determine the origin of most of the atoms in the pyrimidine are described. Based on these studies, a new mechanism for HMP formation is proposed.
ISSN:1477-0520
1477-0539
DOI:10.1039/B405429F