Optimization of critical medium components for enhancing antibacterial thiopeptide nocathiacin I production with significantly improved quality

Chinese Journal of Natural Medicines
Mao-Yu YangYijun Chen

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-1at 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.

References

Sep 25, 2004·Antimicrobial Agents and Chemotherapy·Michael J PucciYasutsugu Ueda
Oct 16, 2004·Bioorganic & Medicinal Chemistry Letters·B Narasimhulu NaiduYasutsugu Ueda
Apr 20, 2006·Bioorganic & Medicinal Chemistry Letters·B Narasimhulu NaiduYasutsugu Ueda
Feb 11, 2009·Biotechnology Progress·Beth JunkerNeal Connors
Jan 29, 2010·Bioresource Technology·Maochen WeiYijun Chen
Mar 23, 2010·Journal of Chromatography. a·Maochen WeiYijun Chen
Dec 12, 2012·The Journal of Pharmacy and Pharmacology·Kun FengYijun Chen

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Citations

Aug 20, 2019·PloS One·M Mofizul Islam, Dennis Wollersheim

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