[Inducible accumulation of alpha-ketoglutaric acid in cultures of Streptomyces hygroscopicus JA 6599 producing a macrolide antibiotic].

The excessive production of pyruvic and 2-oxoglutaric acid by S. hygroscopicus JA 6599 grown on a medium rich in complex carbon and nitrogen sources was studied. Towards the end of the first day of batch cultivation a maximum level of both keto acids in the medium was observed. By diluting the complete culture with water at 22nd hour, however, a further increase in 2-oxoglutarate concentration was induced and the antibiotic production was slightly stimulated. In diluted cultures the oxygen saturation was found to be distinctly higher than in non-diluted ones and, on the other hand, the mycelial activities of both pyruvate and 2-oxoglutarate decarboxylases were decreased. Since the 2-oxoglutarate level was strongly influenced by inhibitors of glycolysis and of citric acid cycle, it is suggested that the metabolite accumulation in diluted cultures is mainly caused by modifications of the metabolic control of carbohydrate catabolism due to an improved aeration. Furthermore, the macrolide antibiotic A 6599 produced by S. hygroscopicus JA 6599 itself was shown to interfere with the accumulation of 2-oxoglutaric acid.