The utilization of purines in the biosynthesis of folic acid.

There is little information on the origin of the pteridine ring of folic acid (1). The possibility that purines contribute to the biosynthesis of this part of the vitamin has been investigated earlier but could not be demonstrated in a number of microorganisms (2). In fact, attempts to demonstrate the conversion of purines to other naturally occurring pteridines have resulted in an impressive number of failures, suggesting that this was not a metabolic pathway (3). On the other hand, in the biosynthesis of riboflavin it has been demonstrated by McNutt (4) that adenine is an effective precursor and from riboflavin-producing molds there have been isolated two pteridines which have been shown to be labeled by radioactive purines. These are 6-methyl-g(1-n-ribityl)-2,4,7-trioxohexahydropteridine obtained by McNutt and Forrest (5,6) and 6,7-dimethyl-8-(n-ribityl) lumazine obtained by Maley and Plaut (7). The latter may be an intermediate in the biosynthesis of riboflavin (7). In view of the failures to obtain evidence for the purine to pteridine conversion in the case of folic acid and other pteridines, it has been suggested that the riboflavin pathway is unique for that vitamin and not of general significance for pteridines (3). In the present work, growing cultures of Corynebacterium sp. from which pteroyltriglutamic acid (teropterin) was first isolated (8) were supplied with labeled adenine. The vitamin was partially purified and degraded chemically through 2-amino4-hydroxypteridine-6-carboxylic acid to 2-amino-bhydroxypteridine (Fig. 1). The latter was examined for radioactivity and gave evidence for an efficient utilization of adenine for the biosynthesis of this part of the vitamin.