Continuous production of a hybrid antibiotic by Streptomyces lividans TK21 pellets in a three-phase fluidized-bed bioreactor.

The continuous production of a hybrid antibiotic by a transformed strain of Streptomyces lividans TK21 in a three-phase fluidized bed is studied. Cell aggregates, known as pellets, are used as immobilized cell particles in the bioreactor. A methodology to prepare pellets of a suitable size and morphology is developed. The continuous production of the antibiotic is studied on the basis of decoupling cell growth and antibiotic production, by means of phosphate limitation in the growth medium. The best results are achieved at D = 0.021 h(1), with alternate feeding of 0 and 0.05 m M phosphate media. Continuous production of the antibiotic can be maintained at satisfactory levels for periods of 60 days, and stable operation of the bioreactor is achieved during 85 days. Finally, the evolution of the internal structure of the pellets during continuous fermentation is studied.