Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process.
Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process.
复制标题
土霉素生物合成基因簇在委内瑞拉链霉菌 WVR2006 中的异源表达，以提高生产水平并改变发酵过程。
DOI：
10.1007/s00253-016-7873-1
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Yang Keqian
中科院分区：
文献类型：
--
作者：
Yin Shouliang;Li Zilong;Wang Xuefeng;Wang Huizhuan;Jia Xiaole;Ai Guomin;Bai Zishang;Shi Mingxin;Yuan Fang;Liu Tiejun;Wang Weishan;Yang Keqian
异源表达是激活次生代谢产物生物合成基因簇的重要策略。在这里，它被用来激活和操纵土霉素（OTC）基因簇，并改变土霉素发酵过程。为了实现这些目标，从几种潜在的宿主中合理地选择了快速生长的异源宿主委内瑞拉链霉菌WVR 2006。它表现出快速而分散的生长和对OTC的内在高耐药性。通过操纵两个集群定位调节器（CSR）OtcR和OtrR的表达和前体供应，OTC生产水平显着增加，在这个异源宿主从75至431 mg/l，仅在48 h，相当于本地生产者Streptomycesrimosus M4018在8天的水平。这项工作表明S. VenezuelaeWVR 2006是一种很有前途的次级代谢产物生产菌，工程化的异源OTC生产菌有可能完全改变OTC生产的发酵过程。
Heterologous expression is an important strategy to activate biosynthetic gene clusters of secondary metabolites. Here, it is employed to activate and manipulate the oxytetracycline (OTC) gene cluster and to alter OTC fermentation process. To achieve these goals, a fast-growing heterologous hostStreptomyces venezuelaeWVR2006 was rationally selected among several potential hosts. It shows rapid and dispersed growth and intrinsic high resistance to OTC. By manipulating the expression of two cluster-situated regulators (CSR) OtcR and OtrR and precursor supply, the OTC production level was significantly increased in this heterologous host from 75 to 431 mg/l only in 48 h, a level comparable to the native producerStreptomyces rimosusM4018 in 8 days. This work shows thatS. venezuelaeWVR2006 is a promising chassis for the production of secondary metabolites, and the engineered heterologous OTC producer has the potential to completely alter the fermentation process of OTC production.