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在模式链霉菌(如天蓝色链霉菌和变铅青链霉菌)中导入许多抗生素生物合成的调控基因可以大幅度提高抗生素的含量。本文报道利用链霉菌的整合质粒克隆几种已知的调控基因,并通过接合转移从大肠埃希菌中导入产生avermectin和多拉菌素的除虫链霉菌工业生产菌株中。发现3种调控基因afsR、aveR和orfX对菌株MMR630中avermectin的含量均可以提高约1倍。但是,以上的3种,加上另外3种调控基因分别导入菌株G11后,发现除afsB提高约13%外,其余调控基因使菌株产生多拉菌素的含量反而有不同程度的降低。将调控基因afsB置于链霉菌强启动子PermE下表达降低了菌株G11中多拉菌素的含量。上述结果表明,调控基因对不同链霉菌的抗生素生物合成具有不同的影响,反映了抗生素生物合成确实受到了复杂网络的调控。
Introduction of many antibiotic biosynthetic genes into Streptomyces patternus (such as Streptomyces coelicolor and Streptomyces lividans) can dramatically increase antibiotic content. Here we report the cloning of several known regulatory genes using an integrated plasmid of Streptomyces and introduction into the industrial strain of S. avermitilis that produces avermectin and doramectin from E. coli via conjugative transfer. It was found that the three regulatory genes afsR, aveR and orfX could increase the avermectin content in strain MMR630 by about 1 time. However, the three above-mentioned genes, together with the other three regulatory genes, were introduced into strain G11, respectively, except that afsB increased by about 13%, the rest of the genes that make the strain to produce doramectin content but with varying degrees of reduction. The expression of the regulatory gene afsB in the Streptomyces strong promoter PermE reduced the content of doramectin in strain G11. The above results indicate that the regulatory genes have different effects on the antibiotic biosynthesis of different Streptomyces and reflect that antibiotic biosynthesis is indeed regulated by a complex network.