Optimization of Streptomyces peucetius var. caesius N47 cultivation and epsilon-rhodomycinone production using experimental designs and response surface methods.

Streptomyces peucetius var. caesius is an aerobic bacterium that produces doxorubicin as a secondary metabolite. A mixture design was applied for the screening of suitable complex medium components in the cultivation of S. peucetius var. caesius N47, which is an epsilon-rhodomycinone-accumulating mutant strain. epsilon-Rhodomycinone is a non-glycosylated precursor of doxorubicin. Best growth results were obtained with soy peptone and beef extract. A central composite face-centered (CCF) experimental design was constructed for the investigation of pH, temperature and dissolved oxygen (DO) effects on the cultivation growth phase. Another CCF was applied to the production phase to investigate the effects of aeration, pH, temperature and stirring rate on epsilon-rhodomycinone production. An increase in cultivation temperature increased both cell growth and glucose consumption rate. Best epsilon-rhodomycinone productivities were obtained in temperatures around 30 degrees C. DO control increased all growth phase responses, but aeration in the production phase coupled with pH decrease resulted in rapid epsilon-rhodomycinone decay in the medium. In non-aerated production phases a pH change resulted in better productivity than in experiments without pH change. A pH increase with a temperature decrease seemed most beneficial for productivity. This implies that dynamic control strategies in batch production of epsilon-rhodomycinone could increase the overall process productivity.