Optimization of critical medium components for enhancing antibacterial thiopeptide nocathiacin I production with significantly improved quality.
10.1016/S1875-5364(17)30047-X
- Author:
Mao-Yu YANG
1
;
Jia-Wei ZHANG
1
;
Xu-Ri WU
2
;
Yi-Jun CHEN
3
Author Information
1. State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing 210009, China.
2. State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xuriwu@cpu.edu.cn.
3. State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: yjchen@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Central composite design;
Nocathiacin I;
Placket-Burman design;
Response surface methodology
- MeSH:
Actinobacteria;
growth & development;
metabolism;
Anti-Bacterial Agents;
biosynthesis;
chemistry;
Bioreactors;
Culture Media;
Fermentation;
Intercellular Signaling Peptides and Proteins;
Peptides;
chemistry;
metabolism;
Quality Improvement
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(4):292-300
- CountryChina
- Language:English
-
Abstract:
Nocathiacin I, a glycosylated thiopeptide antibiotic, displays excellent antibacterial activities against multidrug resistant bacterial pathogens. Previously, a novel nocathiacin I formulation for intravenous administration has been successfully developed and its aqueous solubility is greatly enhanced for clinical application. The purpose of the present study was to increase the fermentation titer of nocathiacin I and reduce or eliminate analogous impurities by screening the medium ingredients using response surface methodology. After a sysmatic optimization, a water-soluble medium containing quality-controllable components was developed and validated, resulting in an increase in the production of nocathiacin I from 150 to 405.8 mg·L at 150-L scale. Meanwhile, the analogous impurities existed in reported processes were greatly reduced or eliminated. Using optimized medium for fermentation, nocathiacin I with pharmaceutically acceptable quality was easily obtained with a recovery of 67%. In conclusion, the results from the present study offer a practical and efficient fermentation process for the production of nocathiacin I as a therapeutic agent.
