Biosynthesis of Vitamin B1 (Thiamin): An Instance of Biochemical Diversity

Abstract

AbstractThe elucidation of the biosynthetic pathway to thiamin (Vitamin B1) and its pyrophosphate ester, the important coenzyme “cocarboxylase”, has challenged researchers for many years and continues to do so. The problem of the origin of thiamin can be separated into three parts: the independent pathways to the pyrimidine moiety 4‐amino‐5‐hy‐droxymethyl‐2‐methylpyrimidine and to the thiazole moiety 5‐(2‐hydroxyethyl)‐4‐methylthiazole, and the route from these subunits to the vitamin. The steps in the latter process were fully established some twenty years ago, and it was shown that the route in aerobic bacteria and yeast differs to some extent from that in enteric bacteria. The pathways to the subunits, on the other hand, are still not clarified. Significant differences exist in the routes whereby each of the two subunits, the pyrimidine moiety and the thiazole moiety, originate in bacteria and yeast. One difficulty that delayed progress was that the incorporation patterns of labeled precursors, which were observed by different research groups in different microorganisms, could not be reconciled on the basis of a single pathway to each of the two subunits. It is now accepted that in each case different pathways exist in enteric bacteria and yeast, and that the biosynthesis of Vitamin B1 represents an instance of biochemical diversity. A second factor that added to the difficulties is the minute amount of thiamin synthesized in microbiological cultures (about 15 μg per L culture). This limited the investigations until very recently either to the use of radioactive tracers or to the use of stable isotopes in conjunction with mass spectrometric analysis. It is widely recognized that both methods are associated with pitfalls in the interpretation of results. High‐field 13C NMR, the most powerful modern method available for the determination of incorporation patterns, has only very recently been successfully employed in investigations of thiamin biosynthesis. As a result of the conceptual and experimental problems, even the primary precursors of each of the two relatively simple heterocyclic subunits of thiamin are still not completely established. A search for committed intermediates, the study of the enzymes, and identification of the genes that are involved are the matter of current research.