Dataset Information

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

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.

SUBMITTER: Yu Z

PROVIDER: S-EPMC6379505 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Yu Zhituo Z Shen Xiaofang X Wu Yuanjie Y Yang Songbai S Ju Dianwen D Chen Shaoxin S

AMB Express 20190218 1

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 op ...[more]

PMID: 30778695

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Project description:Malaria is one of the life-threatening diseases in the world. The spread of resistance to antimalarial drugs is a major challenge, and resistance to artemisinin has been reported in the Southeast Asian region. In the previous study, the active compound of Streptomyces hygroscopicus subsp. Hygroscopicus (S. hygroscopicus), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the Plasmodium parasite, identifying and analyzing the effectiveness of compounds contained in S. hygroscopicus through instrumentation of liquid chromatography/mass spectrometry (LC/MS) and in silico studies were very useful. This study aimed at identifying other derivative compounds from S. hygroscopicus and screening the antimalarial activity of the compound by assessing the binding affinity, pharmacokinetic profile, and bond interaction. The derivative compounds were identified using LC/MS. Protein targets for derivative compounds were found through literature studies, and the results of identification of compounds and protein targets were reconstructed into three-dimensional models. Prediction of pharmacokinetic profiles was carried out using Swiss ADME. Screening of protein targets for the derivative compound was carried out using the reverse molecular docking method. Analyzing bond interaction was done by LigPlot. One compound from S. hygroscopicus, i.e., 6,7-dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione, was successfully identified using LC/MS. This compound was an isoquinoline derivative compound. Through literature studies with inclusion criteria, thirteen protein targets were obtained for reverse molecular docking. This isoquinoline derivative had the potential to bind to each protein target. The pharmacokinetic profile showed that this compound had the drug-likeness criteria. Conclusion. 6,7-Dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione has antimalarial activity as shown by reverse molecular docking studies and pharmacokinetic profiles. The best inhibitory ability of compounds based on bond affinity is with adenylosuccinate synthetase.

Dataset Information

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

Publications

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

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