Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
作者机构：Key Laboratory of Combinatorial Biosynthesis and Drug DiscoveryMinistry of Education and Wuhan University School of Pharmaceutical SciencesWuhan430071PR China CAS Key Laboratory of Quantitative Engineering BiologyShenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518055PR China Hubei Engineering Laboratory for Synthetic MicrobiologyWuhan Institute of BiotechnologyWuhan430075PR China
出 版 物：《Synthetic and Systems Biotechnology》 (合成和系统生物技术（英文）)
年 卷 期：2021年第6卷第4期
页 面：292-301页
核心收录：
学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071005[理学-微生物学] 10[医学]
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
主 题：Spinosyn Spinosad Polyketide Polyketide synthase Heterologous production Streptomyces
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 ***,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 *** 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 *** systematically investigated the result of overexpressing polyketide synthase genes(spnA,B,C,D,E)using a constitutive promoter on the spinosad titer in *** *** supply of polyketide synthase precursors was then increased to further improve spinosad ***,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 *** research provides useful strategies for efficient heterologous production of natural products.
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