几种调控基因对除虫链霉菌工业生产株的抗生素效价的影响

The effects of several regulatory genes on antibiotic productivity of the industrial strains of Streptomyces avermitilis

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。

In the model Streptomyces strains such as Streptomyces ceolicolor and Streptomyces lividans, the antibiotics productivity could be greatly increased by introducing many antibiotic biosynthetic regulatory genes. In this paper, several known regulatory genes were cloned into an integrative vector and were introduced by conjugal transfer from E. coli to the Streptomyces avermitilis industrial stains that produced avermectin or doramectin. The avermectin yield in strain MMR630 increased by about one fold after introducing individually the regulatory genes aveR, afsR or orfX. But in the case of strain G11 by independently introducing with six genes, including the former three genes, the yield of doramectin decreased except the afsB gene increased by 13%. Expression of afsB gene under the constitutive promoter P ermE^＊ decreased the productivity of doramectin of strain Gll. These results indicated that the regulatory genes have differential effects on the antibiotic production of different industrial strains, and suggested that regulatory of antibiotic biosynthesis was indeed involved in a complicated regulation network in Streptomyces.