基于基因功能分析的乳酶生与表飞鸣生产用菌株质量比对研究  

Quality comparison research of Lactasin strain and Biofermin strain based on gene function analysis

作　　者：丁勃 沈振 任丽宏 徐晓洁 邢晟 刘新泳[5] DING Bo;SHEN Zhenn;REN Li-hongg;XU Xiao-jie;XING Sheng;LIU Xin-yong(Shan Dong Institute for Food and Drug Control,Jinan 250101,China;Shandong Food and Drug Safety Testing Engineering Technology Research Center,Jinan 250101,China;NMPA Key Laboratory for Research and Evaluation of Generic Drugs,Jinan 250101,China;Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs,Jinan 250101,China;School of Pharmaceutical Sciences Shandong University,Jinan 250012,China)

机构地区：[1]山东省食品药品检验研究院,济南250101 [2]山东省食品药品安全检测工程技术研究中心,济南250101 [3]国家药品监督管理局仿制药研究与评价重点实验室,济南250101 [4]山东省仿制药一致性评价工程技术研究中心,济南250101 [5]山东大学药学院,济南250012

出　　处：《中国新药杂志》2023年第6期643-656,共14页Chinese Journal of New Drugs

基　　金：国家药典委员会药品标准制修订研究课题:微生态活菌制品分类及标准建立(2020S10)。

摘　　要：目的:利用高通量测序和生物信息学技术,从基因组水平上评价、比较微生态活菌制品乳酶生(乳酶生株)和表飞鸣(表飞鸣株)生产用菌株的安全性和有效性,为微生态活菌制品生产用菌株的质量研究、一致性评价等提供依据。方法:以DIAMOND技术为核心,结合个性化数据库构建检索技术,通过序列比对寻找目标基因并分析其功能。结果:乳酶生和表飞鸣生产用菌株均为屎肠球菌,两株菌的基因组间共线性关系较好,存在少量的插入、缺失、倒位和易位等基因重排事件。表飞鸣株在毒力基因、耐药性基因、细菌素基因、生物胺基因、原噬菌体以及移动遗传元件等6个方面的安全性与乳酶生株相似,但是在包括应激反应基因、抗菌/拮抗活性基因、抗氧化活性基因以及附着力基因等益生性功能等方面,表飞鸣株优于乳酶生株。结论:本文初步建立了基于特定基因功能分析的微生态活菌制品生产用菌株质量评价方法,进一步完善了微生态活菌制品的质量研究和质量评价体系。Objective:To evaluate and compare the safety and efficacy of microecological live bacteria preparations Lactasin(Lactasin strain)and Biofermin(Biofermin strain)production strains at the genome level using high-throughput sequencing and bioinformatics technology,thus to provide basis for the quality research and consistency evaluation of strains used in the production of ecological live bacteria products.Methods:Combined with a personalized database,DIAMOND retrieval strategy was used to find target genes and analyze their functions through sequence comparison.Results:The strains used for Lactasin and Biofermin production were both Enterococcus faecium.The genomes of the 2 strains had good collinearity,but a few of genes had rearrangements such as insertions,deletions,inversions,and translocations.The safety of the Biofermin strain was similar to the Lactasin strain in 6 aspects,including virulence genes,drug resistance genes,bacteriocin genes,biogenic amine genes,prophages and mobile genetic elements.In the evaluation of probiotic function of stress response genes,antimicrobial/antagonistic activity,antioxidant activity genes and adhesion genes,Biofermin strain was better than Lactasin strains.Conclusion:In this paper,a quality evaluation method of strains for the production of microecological live bacteria products was initially established based on specific gene function analysis,and the quality research and quality evaluation system were also improved and perfected for microecological live bacteria products.

关 键 词：乳酶生 表飞鸣 屎肠球菌 生物信息学 功能基因 益生菌筛选 药物一致性评价 

分 类 号：R975[医药卫生—药品]