诱导对庆大霉素的低水平抗性加强微生物合成抗生素的能力(英文)  

Enhanced Antibiotic Production by Inducing Low Level of Resistance to Gentamicin

作　　者：胡海峰[1] 张琴[1] 朱宝泉[1] 

机构地区：[1]上海医药工业研究院,上海200040

出　　处：《中国天然药物》2008年第2期146-152,共7页

基　　金：日本科学技术厅开放融合核糖体工程项目资助~~

摘　　要：目的:通过考察庆大霉素抗性突变株,发现庆大霉素抗性与加强抗生素合成能力之间关系。方法:通过诱导对庆大霉素的低水平抗性,筛选能够加强抗生素合成的突变株;通过在没加抗生素的琼脂平板系列传代,优化突变株的稳定性,并应用蛋白质印迹分析考察加强抗生素的合成与表达两个抗生素生物合成途径中的调节蛋白ActⅡ-ORF4或RedD之间关系。结果:大约3%-20%的庆大霉素低水平抗性突变株(gen)能够加强抗生素的合成水平。在变铅青链霉菌的庆大抗性突变株中,活化Act和Red的合成与过量表达两个抗生素生物合成途径中的调节蛋白ActⅡ-ORF4或RedD之间密切相关。结论:本研究建立一个新的抗生素生产菌株选育方法,即诱导链霉菌和细菌对庆大霉素的低水平抗性。AIM： To investigate the gentamicin-resistant mutants and find the relationship between resistance to gentamicin and enhanced antibiotic production. METHODS： The mutants with low level of resistance to gentamicin were selected and their antibiotic productivity was detected. Moreover, the stability of mutants was improved by a serial passage in the absence of gentami- cin, and the expression of proteins ActⅡ-ORF4 and RedD （ and RedZ） in the mutants and parent were analysized and compared by Western Blotting. RESULTS： Mutants with enhanced antibiotic production were detected at a high frequency （3% to 20% ） compared to traditional strain improving method. Moreover, Western blot analyses revealed that gentamicin-resistant（gen） mutations could activate/enhance actionorhodin （Act） and undecylprodigosin （Red） biosyntheses in Streptomyces lividans through directly or indirectly upregulating the expression of proteins ActⅡ-ORF4 and RedD （ and RedZ）, the Act and Red biosynthesis pathway-specif- ic positive regulators, respectively. CONCLUSION： A rational approach for improving the production of antibiotics in Streptomyces and other bacteria by inducing low level of resistance to gentamicin was developed.

关 键 词：庆大霉素 突变株 链霉菌 抗生素 

分 类 号：R978.1[医药卫生—药品]