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

作　　者：Ziheng An Hui Tao Yong Wang Bingqing Xia Yang Zou Shuai Fu Fang Fang Xiao Sun Renqiong Huang Yao Xia Zixin Deng Ran Liu Tiangang Liu 

机构地区：[1]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery,Ministry of Education and Wuhan University School of Pharmaceutical Sciences,Wuhan,430071,PR China [2]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 [3]Hubei Engineering Laboratory for Synthetic Microbiology,Wuhan Institute of Biotechnology,Wuhan,430075,PR China

出　　处：《Synthetic and Systems Biotechnology》2021年第4期292-301,共10页合成和系统生物技术（英文）

基　　金：This work was supported by the National Key R&D Program of China[grant number 2018YFA0900400];the National Natural Science Foundation of China[grant number 31670090],and J1 Biotech Co.,Ltd.

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.

关 键 词：Spinosyn SPINOSAD POLYKETIDE Polyketide synthase Heterologous production STREPTOMYCES 

分 类 号：Q93[生物学—微生物学]