Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
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...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2021-12-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X2100051X |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ziheng An |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T08:33:44Z |
| format | Article |
| id | doaj.art-a906b9e35a424e13a348659c38ce7244 |
| institution | Directory Open Access Journal |
| issn | 2405-805X |
| language | English |
| last_indexed | 2024-04-24T08:33:44Z |
| publishDate | 2021-12-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-a906b9e35a424e13a348659c38ce72442024-04-16T18:15:41ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2021-12-0164292301Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeletonZiheng An0Hui Tao1Yong Wang2Bingqing Xia3Yang Zou4Shuai Fu5Fang Fang6Xiao Sun7Renqiong Huang8Yao Xia9Zixin Deng10Ran Liu11Tiangang Liu12Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR China; 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; Corresponding author. 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; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan, 430075, PR China; Corresponding author. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR China.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.http://www.sciencedirect.com/science/article/pii/S2405805X2100051XSpinosynSpinosadPolyketidePolyketide synthaseHeterologous productionStreptomyces |
| spellingShingle | 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 Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton Synthetic and Systems Biotechnology Spinosyn Spinosad Polyketide Polyketide synthase Heterologous production Streptomyces |
| title | Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton |
| title_full | Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton |
| title_fullStr | Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton |
| title_full_unstemmed | Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton |
| title_short | Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton |
| title_sort | increasing the heterologous production of spinosad in streptomyces albus j1074 by regulating biosynthesis of its polyketide skeleton |
| topic | Spinosyn Spinosad Polyketide Polyketide synthase Heterologous production Streptomyces |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X2100051X |
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