Medium optimization with the response surface methodology to improve daptomycin production

Abstract:

[Background] Daptomycin is an important antibiotic isolated from Streptomyces roseospoous NRRL 11379 and is clinically used to treat infections. The long fermentation period of the daptomycin producer restricts its productivity. Hence, a daptomycin heterologous expression strain Streptomyces coelicolor K10 that can significantly shorten the fermentation period, was constructed in our previous work. Unfortunately, the very low titer of daptomycin in S. coelicolor K10 hampers its use in further studies. [Objective] The fermentation medium of S. coelicolor K10 was optimized by response surface methodology to improve daptomycin production. [Methods] Plackett-Burman experiment, the steepest ascent method, and response surface methodology were used to optimize the fermentation medium of S. coelicolor K10; and the experiment data were analyzed using Design Expert 8.0. [Results] The main influential factors were dextrin, yeast extract, and casein; and their optimal concentrations were 25.11, 2.20, and 2.00 g/L, respectively. Under the optimal condition, the production of daptomycin could reach 15.30 mg/L, about 2.17 times higher than that in the original medium. [Conclusion] This study increases the daptomycin titer of S. coelicolor K10 considerably and provides a reliable basis for the follow-up studies of daptomycin.