Intermediates in the folic acid biosynthetic pathway are incorporated into molybdopterin the yeast, Pichia canadensis

Biosynthesis of molybdopterin was followed in the yeast, Pichia canadensis, using labeled precursors. High performance liquid chromatography analysis of extracts from cells labeled with [U-¹⁴C]guanosine showed that the label was incorporated into the molybdopterin oxidation product, dephospho Form A. Dephospho Form A isolated from cells labeled with [U- ¹⁴C,5'-³H]guanosine was devoid of tritium, indicating partial loss of the ribose moiety of guanosine during the synthesis of molybdopterin. In vivo labeling of P. canadensis using [7-¹⁴C]neopterin and [6,7,1- ¹⁴C]hydroxymethylpterin led to label from both compounds appearing in dephospho Form A as well as in folic acid in wild type cells. When these labeled precursors were incubated with P. canadensis mutants blocked in molybdopterin synthesis, only folic acid was labeled. These results suggest a shared pathway in the biosyntheses of molybdopterin and folic acid. [6- ¹⁴C]Glucose labeling experiments led to exclusive incorporation into the 4'-position of dephospho Form A but not in folic acid. It is proposed that molybdopterin synthesis branches from the folic acid biosynthetic pathway at dihydrohydroxymethylpterin and that a 3-carbon phosphorylated compound such as glyceraldehyde 3-phosphate may condense with dihydrohydroxymethylpterin to form the 4-carbon side chain precursor to molybdopterin.