Daptomycin antibiotic production processes in fed-batch fermentation by Streptomyces roseosporus NRRL11379 with precursor effect and medium optimization

• Published in: Bioprocess and biosystems engineering Vol. 37; no. 3; pp. 415 - 423
• Main Authors: Ng, I-Son, Ye, Chiming, Zhang, Zhixiang, Lu, Yinghua, Jing, Keju
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2014; Springer Nature B.V
• Subjects: Anti-Bacterial Agents - biosynthesis; Antibiotics; Bioreactors; Biotechnology; Chemistry; Chemistry and Materials Science; Chromatography, High Pressure Liquid; Culture Media; Daptomycin - biosynthesis; Electrophoresis, Polyacrylamide Gel; Environmental Engineering/Biotechnology; Fermentation; Flow rates; Food Science; Industrial and Production Engineering; Industrial Chemistry/Chemical Engineering; Microscopy, Electron, Scanning; Optimization techniques; Original Paper; Pharmaceutical industry; Streptococcus infections; Streptomyces - metabolism; Tandem Mass Spectrometry; Yeasts; Sodium decanoate; Daptomycin antibiotic; Optimization; Fed-batch fermentation
• ISSN: 1615-7591; 1615-7605
• DOI: 10.1007/s00449-013-1007-2

Sodium decanoate was first found to be an effective precursor for synthesis of daptomycin from Streptomyces roseosporus NRRL11379 which was increased to 71.55-fold, compared with decanoic acid. The optimal flow rate of precursor was at 600 mg/(L day) after 48 h fermentation. From protein analysis via SDS-PAGE and identification of Tandem MS/MS afterwards, it deciphered that guanosine pentaphosphate synthetase, PNPase, tripeptidylamino peptidase primarily dealing with daptomycin synthesis. By applying Taguchi’s L16 in culture optimization, the best yield was obtained from the medium with 60 g/L dextrin, 10 g/L dextrose, 1.0 g/L molasses, and 8 g/L yeast extract, respectively. The fed-batch fermentation, applied with feedback control of dextrin, stimulated the production up to 812 mg/L at 288 h. To our best knowledge, the daptomycin production in this study is significantly higher than that in previous studies and can make it more widely used in pharmaceutical industry.