PRODUCTION OF THE MACROLIDE ANTIBIOTIC TYLOSIN IN CYCLIC FED-BATCH CULTURE

Tylosin-producing Streptomyces fradiae was cultured on a synthetic medium with a high glutamate-glucose ratio. Tylosin batch fermentations with this medium were characterized by a high initial specific production rate of tylosin (q//t//y//l//o//s//i//n, mg/g h) that decreased as the fermentation progressed. Continuous feeding of glutamate, glucose, and methyloleate at a constant feed rate initiated during the period of high q//t//y//l//o//s//i//n had been shown to produce some increase in tylosin productivity. By using a cyclic feeding strategy, it was possible to increase tylosin productivity further. Under optimum cyclic conditions it was possible to maintain linear tylosin accretion and a constant value of q//t//y//l//o//s//i//n up to 240 h.