The Direct Precursor of the Pyrimidine Moiety of Thiamin Is Not Urocanic Acid but Histidine in Saccharomyces cerevisiae

Abstract

The biosynthetic route of the pyrimidine moiety of thiamin is different in prokaryotes and eukaryotes. In prokaryotes, the pyrimidine moiety is synthesized from aminoimidazole ribonucleotide, an intermediate of purine biosynthesis, while in eukaryotes, we have reported that the N-1, C-2, and N-3 atoms of the imidazole ring of histidine are incorporated into N-3, C-4, and the amino group attached to the C-4 atoms of the pyrimidine moiety, respectively, as a unit; the rest of the atoms of the pyrimidine moiety originate from pyridoxine as a unit. It has been reported that urocanic acid, the deaminated compound of histidine, is the direct precursor of the pyrimidine moiety. In the present report, we have investigated whether histidine or urocanic acid is the direct precursor of the pyrimidine moiety in Saccharomyces cerevisiae , using tracer experiments with 1) 13 C-formate and urocanic acid, 2) 15 N-NH 4 Cl and urocanic acid, 3) 15 N-NH 4 Cl and histidine, and 4) 13 C-histidine and urocanic acid. The GC-MS analysis revealed that the incorporation of the 15 N atom of 15 NH 4 Cl was not affected by the presence of urocanic acid, although it was affected by histidine, and the incorporation of 13 C-histidine was not affected by the presence of urocanic acid. These results confirm that histidine is the direct precursor of the pyrimidine moiety of thiamin in S. cerevisiae .

Discovery of a SAR11 growth requirement for thiamin’s pyrimidine precursor and its distribution in the Sargasso Sea

“…P. ubique was 0.29±0.03 per day (mean±s.d., n ¼ 123) and did not vary with vitamin or precursor treatments (for example, see Supplementary Figure S6). To rule out NMT1 activity as a potential source of HMP, thiamin was replaced with histidine and vitamin B 6 (NMT1's substrates; Ishida et al, 2008). Consistent with the prediction that Ca.…”

The Structural and Biochemical Foundations of Thiamin Biosynthesis

“…Thi5 generates the HMP moiety using pyridoxine and histidine (112, 113). HMP is subsequently pyrophosphorylated by Thi20 (114).…”

Plasticity in the Purine–Thiamine Metabolic Network of Salmonella

“…In some organisms such as yeast, the synthesis of the HMP moiety does not involve an intermediate metabolite in purine biosynthesis and depends on histidine as an HMP precursor (Tazuya et al 1989(Tazuya et al , 1993Maundrell 1990;Ishida et al 2008). However, to our knowledge, this is the first demonstration that the early purine enzymes can be bypassed for thiamine synthesis in bacteria.…”