新型抗真菌抗生素尼可霉素Z高产菌株的育种

发布时间：2018-04-30 05:29

本文选题：几丁质合成酶抑制剂 + 抗真菌药物　；参考：《中国抗生素杂志》2015年09期

【摘要】：目的以唐德链霉菌Streptomyces tendae ATCC 31160为原始菌株,通过选育获得高产突变株,并研究高产菌株的工业化发酵工艺。方法根据尼可霉素Z的生物合成途径,通过离子束注入方法,选育对关键中间产物2-吡啶-甲醛(PA)和3-甲基天冬氨酸的结构类似物S-(2-氨基乙基)-L-半胱氨酸(AEC)具有耐受性的突变菌株,使突变菌株的代谢能够朝着产物NIK合成的方向。结果最终筛选到一支高产突变菌株,其抗生素产量达到3000mg/L,较出发菌株提高150倍以上。在此基础上,建立了小试发酵工艺路线。结论高产突变株的筛选和发酵工艺的确定为该项目产业化奠定了基础。
[Abstract]:Objective to obtain high yield mutant from Streptomyces Streptomyces tendae ATCC 31160, and to study the industrial fermentation process of high yield strain. Methods according to the biosynthesis pathway of Nikomycin Z, ion beam implantation was used. The mutant strains with tolerance to the key intermediates 2-pyridine-formaldehyde) and the structural analogues of 3-methylaspartic acid (S-Pa-2-aminoethyl-L-cysteine) were selected. The metabolism of the mutant strains could be directed towards the direction of NIK synthesis. Results A mutant strain with high yield was screened, and the antibiotic yield reached 3000 mg / L, which was more than 150 times higher than that of the original strain. On the basis of this, the technological route of small scale fermentation was established. Conclusion the screening of high-yield mutant and the determination of fermentation technology laid a foundation for industrialization of the project.
【作者单位】：浙江省抗真菌药物重点实验室浙江海正药业股份有限公司;
【基金】：十二五“重大新药创制”科技重大专项(2012ZX09201101-004),(2012ZX09103101-075) 浙江省科技计划项目(2009C33019) 台州市-浙江大学科技合作专项(08ZJU007) 浙江省抗真菌药物重点实验室建设项目(2007E10005);浙江省抗真菌药物重点实验室开放课题
【分类号】：R978.5

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