Regulative influence of o ‐aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b II. Regulation of glutamine synthetase and the role of the glutamine synthetase/glutamate synthase pathway

In S. noursei JA 3890b which produces nourseothricin, a streptothricin‐type antibiotic, the participation of the glutamine synthetase/glutamate synthase pathway in the regeneration of glutamic acid was established. Glutamate synthase of this organism requires 2‐ketoglutarate, glutamine, and NADH for glutamate production. The glutamine synthetase/glutamate synthase pathway is considered to operate both in the assimilation of low levels of ammonia and in the nitrogen catabolism of amino acids, e. g. of alanine. Thus, the activity of glutamine synthetase increased in cultures grown on a soluble medium after the pool of NH + 4 was exhausted. The synthesis of this ‘assimilative’ type of enzyme was found to be repressed by increased amounts of ammonium ions in the medium. High intramycelial levels of glutamine synthetase even in the presence of high concentrations of ammonium ions were found if the strain was cultivated on a medium containing an additional source of nitrogen, e. g. alanine or some other amino acids. Simultaneously, in these cultures the activity of alanine dehydrogenase was enhanced, suggesting that this enzyme cooperates with the ‘amphibolic’ type of glutamine synthetase in the catabolism of amino acids. o‐Aminobenzoic acid (OAB, anthranilic acid) a known stimulator of the biosynthesis of nourseothricin by S. noursei JA 3890b was shown to exert a repressory effect on the formation of both the ‘amphibolic’ type of glutamine synthetase and the alanine dehydrogenase. The capacity of o ‐aminobenzoic acid to regulate diverging pathways of amino acid metabolism was further demonstrated by its stimulatory effect on the production of NADP‐specific glutamate dehydrogenase.