发酵科技通讯2024,Vol.53Issue(4) :237-242.

达托霉素高产菌株选育及补料工艺研究

Study on the breeding of high-yield strain of daptomycin and its feeding technology

张莉 赵建强 郄丽萍 李晓露 刘雨 赵鹏鹏 张雪霞
发酵科技通讯2024,Vol.53Issue(4) :237-242.

达托霉素高产菌株选育及补料工艺研究

Study on the breeding of high-yield strain of daptomycin and its feeding technology

张莉 1赵建强 2郄丽萍 1李晓露 1刘雨 2赵鹏鹏 1张雪霞1
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作者信息

  • 1. 华北制药集团新药研究开发有限责任公司,河北石家庄 052165
  • 2. 华北制药华胜有限公司,河北石家庄 052160
  • 折叠

摘要

通过选育达托霉素高产菌株以及优化前体物质的补料工艺来提高发酵产量.采用常压室温等离子体(Atmospheric room temperature plasma,ARTP)诱变,结合链霉素和利福平抗性育种方法,在低溶氧发酵体系下对达托霉素突变株进行筛选,获得了高产菌株DT-SR-18,其摇瓶发酵水平较出发菌株提高了 36.2%.以癸酸钠作为达托霉素合成的前体物质,在50 L罐优化了癸酸钠的补料工艺.研究结果表明:在发酵培养24 h后,以0.5 mL/(h·L)恒定速度流加25%的癸酸钠溶液,其500 L罐发酵产量平均达到2 351 μg/mL,达托霉素的发酵水平大幅提高.

Abstract

The fermentation production was enhanced by breeding a high-yield strain of daptomycin and optimizing the feeding process of the precursor substance.Experiments demonstrated that the high-yield strain DT-SR-18 was obtained via the atmospheric pressure room temperature plasma(ARTP)mutagenesis combined with streptomycin and rifampicin resistance breeding under a low-oxygen solution fermentation system.Compared to the original strain,the shaking flask fermentation production of DT-SR-18 increased by 36.2%.In a 50 L tank,the feeding process of sodium caprate as a precursor for daptomycin synthesis was optimized.Results showed that adding 25%sodium caprate solution at a constant rate of 0.5 mL/(h·L)over 24 hours led to a fermentation production of 2 351 μg/mL in a 500 L tank,significantly improving the yield of daptomycin.

关键词

达托霉素/玫瑰孢链霉菌/ARTP/抗性/癸酸钠

Key words

daptomycin/Streptomyces roseosporus/ARTP/resistance/sodium caprate

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出版年

2024
发酵科技通讯
中国发酵工业协会,杭州西湖味精集团有限公司

发酵科技通讯

影响因子:0.311
ISSN:1674-2214
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