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抗性突变他克莫司高产菌株的选育
引用本文:袁晖,张新宜,王欣荣.抗性突变他克莫司高产菌株的选育[J].微生物学杂志,2014(5):81-86.
作者姓名:袁晖  张新宜  王欣荣
作者单位:[1]四川抗菌素工业研究所抗生素研究与再评价四川省重点实验室,四川成都610052; [2]上海新亚药业有限公司,上海200252
基金项目:“重大新药创制”科技重大专项“国药集团技术创新产学研联盟建设”(2011ZX09401-403)
摘    要:研究利用核糖体工程育种方法结合紫外诱变处理产他克莫司链霉菌SIIA-9818,以期筛选得到发酵水平有较大提高的新菌株。首轮采用链霉素抗性筛选,第二轮组合链霉素和利福平抗性结合紫外诱变育种,进一步巩固育种成效。采用链霉素抗性诱变得到突变株T-122,其气生菌丝丰满程度明显好于原对照株,发酵效价提高22.8%;采用组合链霉素和利福平抗性结合紫外诱变T-122,得到多株高产菌株,其中H-493发酵水平较原出发菌株提高82.6%;在50 L发酵罐通过增大搅拌转速,使菌种H-493发酵单位进一步提高31.0%。本方法简单经济,得到的突变株发酵单位显著提高,组分无明显变化,传代稳定。

关 键 词:他克莫司  核糖体工程  发酵  抗性突变

Breeding of Resistant Mutant Tacrolimus-High-Producing Streptomyces Strain SIIA-9818
YUAN Hui,ZHANG Xin-yi and WANG Xin-rong.Breeding of Resistant Mutant Tacrolimus-High-Producing Streptomyces Strain SIIA-9818[J].Journal of Microbiology,2014(5):81-86.
Authors:YUAN Hui  ZHANG Xin-yi and WANG Xin-rong
Institution:YUAN Hui, ZHANG Xin-yi, WANG Xin-rong(1. Antibiotics Res. & Re-Profil. Key Lab of Sichuan Proe. ,Sichuan lndust. Inst. of Antibiotics Chengdu 610052; 2. Shanghai Xinya Pharm. Co. , Ltd, Shanghai 200252)
Abstract:Breeding using ribosome engineering method combined with UV mutation treatment was studied so as to screen and obtain a new tacmlimus producing strain of Streptomyces qianfoensis SIIA-9818 with a promoted production.The first round adopted streptomycin resistance screening; the second round adopted streptomycin resistance and rifampicin resistance combined with UV mutation breeding,to strengthen further the breeding effects.The mutant strain T-122 was obtained adopting streptomycin resistance mutation,the well-growth of its aerial hyphal was significantly far better than the original control strain,and the fermentation titer was increased by 22.8% ; while the one adopting combination of streptomycin resistance and rifampicin resistance and UV mutation,obtained many high producing strains,among them the fermentation level of H-493 increased by 82.6% ; the fermentation titer was improved by 31.0% in 50 L-fermentor by increasing stir rpm.This method is simple and economic,and the obtained mutant strain' s fermentation unit was noticeably improved,with no apparent changes of its components,and stable generations conveyance.
Keywords:tacrolimus  antibiotic-resistance mutation  ribosome engineering  fermentation
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