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基于核糖体工程技术的泰乐菌素高产菌株选育研究
牛春,丁亚莲,张萍
0
(宁夏泰瑞制药股份有限公司)
摘要:
为了进一步提高泰乐菌素的产量满足生产需求。我们从生产实践中选出一株优良菌株T19-805,利用多次引入抗生素的核糖体工程育种技术,选用的7种抗生素中有4种抗生素(林可霉素、硫链丝菌素、链霉素与遗传霉素)对泰乐菌素产量有了大幅度提高。经过三轮抗性筛选获得一株含4重抗生素的高产突变株Tltsg-69,产量达到16507 μg/mL,将原始出发菌株T19-805(12000μg/mL)提高了37.6%,该菌株连续培养5代,其化学效价基本稳定,具有较好的遗传稳定性。结果表明,利用核糖体工程育种方法能有效地提高泰乐素产量。
关键词:  核糖体工程  泰乐菌素  高产菌株
DOI:
投稿时间:2022-04-25修订日期:2022-10-17
基金项目:
Study on the Breeding of High-yield Strain of Tylosin Based on Ribosome Engineering Technology
(Ningxia Tairui Pharmactlal Co.,Ltd)
Abstract:
In order to further improving the yield of tylosin. We pick out one good strains T19-805 from production practice. Four effective antibiotics were identified from seven antibiotics with high mutation to the original strain T19-805 with ribosome engineering. So, lincomycin, thiostrepton, streptomycin and geneticin were selected as the resistance marker of mutagenesis. The highest-yield mutant Tltsg-69 was generated after three rounds of screening, the tylosin chemical titer reached 16507 μg/mL, increased 37.6 % than the original strain T19-805. After continuously cultured for 5 generations the strain had basically stable chemical titer and better hereditary stability. In conclusion, Ribosome engineering requires less cost than other methods and may be widely utilized for bacterial strain improvement. In conclusion, the method of ribosome engineering may be effective as one of the strategies to enhance productionof tylosin.
Key words:  ribosome engineering  tylosin  high-yield strain

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