Biosynthese des Makrolid‐Antibioticums A 6599 durch Streptomyces hygroscopicus JA 6599 und Aktivität des NADP‐abhängigen Stoffwechsels

The activities of some NADP‐specific enzymes and of corresponding metabolic pathways were studied in mycelium extracts of Streptomyces hygroscopicus JA 6599 strains producing different yields of the macrolide antibiotic A 6599. Isocitrate dehydrogenase (EC 1.1.1.40) was the most active NADP‐specific enzyme in a higher producing (B) and in a low producing strain (A) grown on complex or synthetic media. Glucose catabolism via hexosomonophosphate pathway as also NADP‐specific decarboxylation of malic acid may contribute to NADPH‐regeneration less than isocitrate oxidation. In strain B increased activities of glucose‐6‐phosphate dehydrogenase (EC 1.1.1.49) and of some tricarboxylic acid cycle enzymes were found but in the low producing strain A NADP‐specific glutamate dehydrogenase (EC 1.4.1.4) was more active. The results point to the importance of NADPH‐production in the biosynthesis of secondary metabolite A 6599 and may indicate also a competition for this coenzyme between antibiotic biosynthesis and formation of glutamic acid. The discussions regarding the connection of tricarboxylic acid cycle activity and NADPH‐regeneration are supported from studies of effector influence on metabolism and antibiotic production.