Discovery of a new nosiheptide-producing strain and its fermentation optimization for nosiheptide production
10.11665/j.issn.1000-5048.20220612
- VernacularTitle:一株诺西肽产生菌的发掘及发酵条件优化
- Author:
Qihang SUN
1
;
Yuncong XU
;
Lingrui WU
;
Jiale RONG
;
Yanwen WANG
;
Yudan CAO
;
Chen LUO
;
Xuri WU
Author Information
1. 中国药科大学生命科学与技术学院生物化学教研室
- Publication Type:Journal Article
- Keywords:
nosiheptide;
genome mining;
fermentation;
biosynthetic gene cluster;
glycosyltransferase
- From:
Journal of China Pharmaceutical University
2022;53(6):725-733
- CountryChina
- Language:Chinese
-
Abstract:
Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.
