Kinetics of the repression of tylosin biosynthesis by ammonium ion in Streptomyces fradiae.

Nitrogen regulation of tylosin synthesis in Streptomyces fradiae NRRL 2702 was studied in batch and chemostat cultures using a soluble synthetic medium. In batch cultures, valine dehydrogenase (VDH; EC 1.4.1.8), threonine dehydratase (TDT; EC 4.2.1.16) and aspartate aminotransferase (ASAT; EC 2.6.1.1) reached their highest specific activities at 120 h. The specific activities of the three enzymes showed close correlation with the value of specific tylosin formation rate (qTYL). In chemostat cultures, the maximum value of qTYL was 1.14 tylosin per mycelial mass per h (mg g-1 h-1) at the specific growth rate of 0.05 h-1, and after reaching a rate of 0.1 h-1, qTYL decreased with increasing levels of the specific growth rate. This value of qTYL was 3.5-times as large as that of maximum qTYL observed in the batch culture. The specific formation rates of VDH, TDT, ASAT and tylosin were repressed by high levels of specific ammonium ion uptake rate.