Metabolic regulation in tylosin-producing Streptomyces fradiae: phosphate control of tylosin biosynthesis.

The effects of increased concentration of inorganic phosphate on the biosynthesis of tylosin, the level of the intracellular adenylates, the energy charge, and the activities of enzymes involved in the synthesis of tylonolide precursors were studied in Streptomyces fradiae NRRL 2702. No metabolic response was observed when elevated levels of inorganic phosphate were added in idiophase. Increased initial levels of inorganic phosphate suppressed tylosin production and markedly increased the levels of the adenylates, although the adenylate energy charge was unchanged. Higher growth and glucose uptake rates were also observed. The activities of methylmalonyl-coenzyme A carboxyltransferase (EC 2.1.3.1) and propionyl-coenzyme A carboxylase (EC 6.4.1.3) were suppressed by the increased concentration of inorganic phosphate. The results indicated that the rate of tylosin synthesis was inversely related to the absolute level of the adenylates rather than to the energy charge.