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ARTP诱变及高通量筛选选育米尔贝霉素高产菌株
张莉,米贯东,戴梦,谢新宇,安兰兰,马婕,任风芝
0
(华北制药集团新药研究开发有限责任公司)
摘要:
为选育米尔贝霉素(milbemycin)优良菌株,提高发酵产量,以吸水链霉菌(Streptomyces hygroscopicus)MB230906作为出发菌株,通过常压室温等离子体(ARTP),结合自身代谢产物抗性,以及高通量筛选技术,获得了1株遗传性状稳定的高产突变菌株AM2405-228,50 L罐发酵产量平均达到3494 μg/mL,较出发菌株提升28.31%,A3:A4达到了1:3.98。结果表明,运用ARTP诱变结合抗性和高通量筛选,可以高效、快速获得发酵产量显著提高的米尔贝霉素突变株,为进一步推进米尔贝霉素的工业化生产奠定坚实的研究基础。
关键词:  米尔贝霉素  吸水链霉菌  ARTP  高通量筛选
DOI:
投稿时间:2024-11-27修订日期:2025-03-05
基金项目:河北省生物合成高能级技术创新中心补助经费
Breeding of Milbemycin High-yield Strain by ARTP Mutagenesis and High-throughput Screening
(New Drug Research & Development Company of NCPC)
Abstract:
In order to breed an excellent strain of milbemycin and improve the fermentation yield, the Streptomyces hygroscopicus MB230906 was used as the starting strain.Through the atmospheric pressure room temperature plasma (ARTP) combined with self-metabolite resistance and high-throughput screening technology, a high-yield mutant strain AM2405-228 with stable heredity was obtained. The average fermentation yield of 50 L tank reached 3494 μg/mL, which was 28.31% higher than that of the original strain, and the ratio of A3:A4 reached 1:3.98. The result showed that ARTP mutagenesis combined with resistance and high-throughput screening could efficiently and rapidly obtain milbemycin mutants with significantly increased fermentation yield, which laid a solid research foundation for further promoting the industrial production of milbemycin.
Key words:  milbemycin  Streptomyces hygroscopicus  ARTP  high-throughput screening

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