Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton

Synthetic and Systems Biotechnology

Tiangang Liu¹  Hui Tao²  Fang Fang²  Yao Xia²  Xiao Sun²  Ziheng An²  Shuai Fu²  Bingqing Xia²  Ran Liu²  Yang Zou²  Yong Wang²  Renqiong Huang²  Zixin Deng² 

[1] CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China;Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR China;

关键词: Spinosyn;    Spinosad;    Polyketide;    Polyketide synthase;    Heterologous production;    Streptomyces;   

DOI  :  

来源: DOAJ

【 摘 要 】

Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete, Saccharopolyspora spinosa. However, their large-scale overproduction is hindered by poorly understood bottlenecks in optimizing the original strain, and poor adaptability of the heterologous strain to the production of spinosyn. In this study, we genetically engineered heterologous spinosyn-producer Streptomyces albus J1074 and optimized the fermentation to improve the production of spinosad (spinosyn A and spinosyn D) based on our previous work. We systematically investigated the result of overexpressing polyketide synthase genes (spnA, B, C, D, E) using a constitutive promoter on the spinosad titer in S. albus J1074. The supply of polyketide synthase precursors was then increased to further improve spinosad production. Finally, increasing or replacing the carbon source of the culture medium resulted in a final spinosad titer of ∼70 mg/L, which is the highest titer of spinosad achieved in heterologous Streptomyces species. This research provides useful strategies for efficient heterologous production of natural products.

【 授权许可】

Unknown