Biosynthesis of thiamine

Abstract

A review of the reported investigations on the biosynthesis of the two heterocyclic moieties of thiamine, i.e. 4-methyl-5-(β-hydroxyethyl)thiazole (HET) and 2-methyl-4-amino-5-hydroxymethylpyrimidine (pyramine), is presented. The subjects covered by the authors are essentially the discovery of precursor molecules, and the pathways followed by the atoms from the precursors to the final metabolites, which sometimes gave important clues to the mechanisms involved. The biological material included some prokaryotic cells (Escherichia coli, Salmonella typhimurium...) and eukaryotic cells (yeasts). Within these limits, the authors have tried to give a complete coverage of the subject. Many problems were solved by the incubation of cells with labeled metabolites - sometimes specifically prepared to obtain a particular answer - and location of the labeled atoms in the metabolites. However, because of the very low concentration of thiamine in wild cells, the techniques for the preparation of cells derepressed for the synthesis of thiamine were found to be very useful, if not indispensable. Great attention is given to some salient features in the biosynthesis of thiamine: in prokaryotic cells, L-tyrosine and 1-deoxy-D-threo-pentulose are the precursors of HET, while aminoimidazole ribotide is the precursor of pyramine. In yeast cells, pyramine comes from L-histidine. Among other results, these studies have unravelled a unique transformation of aminoimidazole ribotide, the known precursor of purines, into a substituted pyrimidine. Moreover, the three missing carbon atoms necessary to the synthesis of pyramine from imidazole-ribotide are supplied by the ribose, and the transformation occurs without separation of the sugar from the imidazole. © CNRS-Gauthier-Villars.