NITROGEN CATABOLITE REGULATION OF STREPTOTHRICIN BIOSYNTHESIS BY STREPTOMYCESNOURSEI JA 3890 b

ABSTRACT The production of nourseothricin, a streptothricin-type antibiotic, by Streptomyces noursei JA 3890b is subject to control by nitrogen catabolites. Due to the peculiarities of the respiratory system and the regulation of the anabolic glutamate dehydrogenase disclosing the repression of enzyme synthesis by NH 3 , there is a high rate of oxidative deamination of amino acids during the growth phase, giving rise to the accumulation of nitrogen catabolites (NH3) within the mycelium and the medium. As was demonstrated by elucidation of the ‘bistability’ phenomenon, anthranilic acid (OABA) and some other effectors are capable of switching over the metabolic flux by virtue of their interaction with the respiratory chain and the amino acid transport. These effects are coupled with considerable stimulation of nourseothricin production, suggesting that repressive interactions of nitrogen catabolites are abolished from the secondary metabolism and that there is a highly improved supply of the biogenetic precursors of nourseothricin. KEYWORDS Streptothricin biosynthesis; Streptomyces noursei JA 3890b; nitrogen catabolite regulation of secondary metabolism; repression by NH 3 of glutamate dehydrogenase formation; stimulation of streptothricin production by effectors; bistability of metabolism; switch over of metabolic flux.