基于核糖体工程技术的泰乐菌素高产菌株的选育研究

Study on the Breeding of High-yield Strain of Tylosin Based on Ribosome Engineering Technology

为进一步提高泰乐菌素的产量满足生产需求,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,泰乐菌素产量达到16507μg/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菌素产量。

In order to further improve the yield of tylosin,we pick out one good strains T19-805 from production practice.Four from seven antibiotics were identified 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 16507μg/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,the method of ribosome engineering may be effective as one of the strategies to enhance productionof tylosin.