The accumulation of orotic acid by a pyrimidineless mutant of Neurospora

The discovery of orotic acid (1,2-carboxyuracil) in cow's milk by Biscaro and Belloni (1), followed by its identification and synthesis (2-4), led to a number of speculations as to its biological origin and significance (,3,5,6). A definite connection of orotic acid with the biosynthesis of nucleic acid pyrimidines is provided by the finding that orotic acid (7) as well as thymine (8,9) can supplement or replace the folic acid required by certain microorganisms. As suggested by Chattaway (7), it would appear that folic acid has a function in the biosynthesis of pyrimidines. Furthermore, this function is probably concerned in some step prior to the appearance of orotic acid in the biosynthetic series. More recently it was shown by Loring and Pierce (10) that orotic acid could be substituted for uracil in satisfying the growth requirements of some pyrimidineless mutants of the mold Neurospora. Investigations of orotic acid in this laboratory have led to a new method of synthesis of the compound (11) and to some suggestions concerning its relation to the biosynthesis of nucleic acids in Neurospora (12). The results of the present work are in accord with the previous suggestions and provide further evidence on the biological origin and function of orotic acid