Symbiotic biosynthesis of folic acid-like growth factors.

Although the postulate that p-aminobenzoic acid (PABA) functions as a precursor of a folic acid-like compound in the metabolism of microorganisms is widely accepted, there is little or no information on the possible intermediates which may be involved in this pathway of synthesis. There still may be some question as to the exact nature of the active end product but the more recent data concerned with the activities of N'0formyltetrahydrofolic acid have been very suggestive (Greenberg, 1954; Jaenicke, 1955). Knowledge of many metabolic systems has been greatly advanced by the studies on mutants of Neurospora crassa which received much impetus from the work of Beadle (1945), and Tatum and Bonner (1944). This study of mutants in relation to the biosynthesis of various metabolites was further extended to Escherichia coli by many investigators. From such studies on E. coli mutants Davis and co-workers have presented some rather interesting data dealing with the synthesis of aromatic compounds, including PABA, and demonstrated the accumulation of intermediates by certain mutants (Davis, 1951). The accumulation of these as well as other intermediates may be demonstrated by the phenomenon of syntrophism (Davis, 1950). Attempts to extend this type of study to the biosynthesis of folic acid (FA) have not met with much success, because the attempts to develop mutants which require FA have not been successful. This failure may be explained by considering FA merely as a side reaction of the main metabolic pathway, and the utilization of FA would therefore depend on the presence of a special enzyme not common to most microorganisms. The response of numerous stock strains of microorganisms to compounds related to FA is a well-documented phenomenon. The organism 1 This investigation was supported in part by a grant-in-aid from the National Science Foundation.