首页|他克莫司高产菌株选育及发酵配方优化

他克莫司高产菌株选育及发酵配方优化

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目的 选育他克莫司高产菌株,优化培养基配方,提高发酵产量.方法 采用原生质体融合技术对2株筑波链霉菌进行基因组重排,并经响应面设计对发酵培养基配方进行优化.结果 以紫外灭活作为遗传标记经过4轮基因组重排育种后,摇瓶筛选获得3株高产菌株,其中菌株FK22-71菌丝球松散、椭圆状,发酵浸泡液颗粒状.该菌株稳定高产,采用响应面设计优化后的配方在50 L罐发酵产量平均达1684 mg/L.结论 基因组重排技术应用于他克莫司高产菌株选育,可大幅提高发酵产量,为其工业化发酵生产奠定了基础.
Breeding of tacrolimus high-yield strain and optimization of fermentation conditions
Objective Breeding high-yield strains of tacrolimus and optimizing the culture medium formula to improve the fermentation unit.Methods The protoplast fusion technique was used to rearrange the genome of two Streptomyces tsuknbaenis strains,and the fermentation medium was optimized by response surface design.Results After four rounds of genome shuffling breeding with UV inactivation as genetic marker,three high-yield strains were obtained by shaking flask screening.Among them,the mycelium ball of strain FK22-71 was loose and oval,and the fermentation soaking liquid was granular.In 50 L fermentor,the average production of tacrolimus reached 1684 mg/L under the response surface optimization by the strain FK22-71,which was steady and high-yielding.Conclusion The application of genome shuffling technology in the breeding of high-yielding tacrolimus producing strains can significantly increase production and lay the foundation for industrial fermentation production.

Genome shufflingTacrolimusResponse surface designMedium optimization

王会会、赵建辉、孙术超、刘雨、任风芝、赵建强

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微生物药物国家工程研究中心,石家庄市微生物药物技术创新中心,华北制药集团新药研究开发有限责任公司,石家庄 052165

华北制药华胜有限公司,石家庄 052160

基因组重排 他克莫司 响应面设计 培养基优化

河北省科技研发平台建设专项石家庄市技术创新中心绩效后补助

22567651H237790659A

2024

中国抗生素杂志
中国医药集团总公司四川抗菌素工业研究所,中国医学科学院医药生物技术研究所

中国抗生素杂志

CSTPCD北大核心
影响因子:1.08
ISSN:1001-8689
年,卷(期):2024.49(2)
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