Hydroxyanthranilic Acid as a Precursor of Nicotinic Acid in Neurospora

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Abstract
Kynurenine is an intermediate product in the synthesis of nicotinic acid from tryptophane in Neurospora. From its structural formula it can be seen that the pyridine ring of nicotinic acid might arise by ring closure of the a keto acid corresponding to kynurenine to give kynurenic acid, which does occur in nature, or, if preceded by oxidation, xanthurenic acid. These compounds plus nicotinic acid derivatives such as the carboxy, hydroxy, amino, methyl, and chloro- pyridines have been found to have no growth-promoting activity on Neurospora cultures with the exception of 3-carboxy 4-amino pyridine, which shows slight activity. Therefore the pyridine ring does not arise from kynurenine through kynurenic acid or xanthurenic acid followed by oxidation. Also evident is that oxidation in position 8 of xanthurenic acid precedes formation of the pyridine ring, a possible intermediate being 3-hydroxy kynurenine; which might undergo biological oxidation to 3 hydroxyanthranilic acid (2-amino 3-hydroxy benzoic acid). Hydroxy-anthranilic acid possesses growth-promoting activity comparable to nicotinamide as shown by the fact that Neurospora (mutant strain #65001) gave almost identical growth curves with nicotinamide and hydroxyanthranilic acid. Hydroxyanthranilic acid activity on several other mutant strains was detd. In an excess of hydroxyanthranilic acid in a Neurospora culture, nicotinamide activity was noted in the culture fluid, and detd. by testing with a strain of Neurospora not responsive to hydroxy anthranilic acid but to either nicotinic acid or nicotinamide. This phenomenon is well known with kynurenine.