Enhancement of ascomycin production via a combination of atmospheric and room temperature plasma mutagenesis in Streptomyces hygroscopicus and medium optimization

AMB Express

Zhituo Yu¹  Dianwen Ju¹  Yuanjie Wu²  Shaoxin Chen²  Songbai Yang²  Xiaofang Shen² 

[1] Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University;Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry;

关键词: Streptomyces hygroscopicus;    Ascomycin;    Atmospheric and room temperature plasma;    Response surface methodology;    Medium optimization;   

DOI  :  10.1186/s13568-019-0749-x

来源: DOAJ

【 摘 要 】

Abstract Ascomycin, a key intermediate for chemical synthesis of immunosuppressive drug pimecrolimus, is produced by Streptomyces hygroscopicus var. ascomyceticus. In order to improve the strain production, the original S. hygroscopicus ATCC 14891 strain was treated here with atmospheric and room temperature plasma to obtain a stable high-producing S. hygroscopicus SFK-36 strain which produced 495.3 mg/L ascomycin, a 32.5% increase in ascomycin compared to the ATCC 14891. Then, fermentation medium was optimized using response surface methodology to further enhance ascomycin production. In the optimized medium containing 81.0 g/L soluble starch, 57.4 g/L peanut meal, and 15.8 g/L soybean oil, the ascomycin yield reached 1466.3 mg/L in flask culture. Furthermore, the fermentation process was carried out in a 5 L fermenter, and the ascomycin yield reached 1476.9 mg/L, which is the highest ascomycin yield reported so far. Therefore, traditional mutagenesis breeding combined with medium optimization is an effective approach for the enhancement of ascomycin production.

【 授权许可】

Unknown