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Flaviolin-Like Gene Cluster Deletion Optimized the Butenyl-Spinosyn Biosynthesis Route in Saccharopolyspora pogona.
He, Haocheng; Tang, Jianli; Chen, Jianming; Hu, Jinjuan; Zhu, Zirong; Liu, Yang; Shuai, Ling; Cao, Li; Liu, Zhudong; Xia, Ziyuan; Ding, Xuezhi; Hu, Shengbiao; Zhang, Youming; Rang, Jie; Xia, Liqiu.
Afiliación
  • He H; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Tang J; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Chen J; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Hu J; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Zhu Z; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Liu Y; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Shuai L; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Cao L; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Liu Z; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Xia Z; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Ding X; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Hu S; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Zhang Y; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Rang J; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
  • Xia L; Hunan Provincial Key Laboratory for Microbial Molecular Biology, State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410083, China.
ACS Synth Biol ; 10(10): 2740-2752, 2021 10 15.
Article en En | MEDLINE | ID: mdl-34601869
Reduction and optimization of the microbial genome is an important strategy for constructing synthetic biological chassis cells and overcoming obstacles in natural product discovery and production. However, it is of great challenge to discover target genes that can be deleted and optimized due to the complicated genome of actinomycetes. Saccharopolyspora pogona can produce butenyl-spinosyn during aerobic fermentation, and its genome contains 32 different gene clusters. This suggests that there is a large amount of potential competitive metabolism in S. pogona, which affects the biosynthesis of butenyl-spinosyn. By analyzing the genome of S. pogona, six polyketide gene clusters were identified. From those, the complete deletion of clu13, a flaviolin-like gene cluster, generated a high butenyl-spinosyn-producing strain. Production of this strain was 4.06-fold higher than that of the wildtype strain. Transcriptome profiling revealed that butenyl-spinosyn biosynthesis was not primarily induced by the polyketide synthase RppA-like but was related to hypothetical protein Sp1764. However, the repression of sp1764 was not enough to explain the enormous enhancement of butenyl-spinosyn yields in S. pogona-Δclu13. After the comparative proteomic analysis of S. pogona-Δclu13 and S. pogona, two proteins, biotin carboxyl carrier protein (BccA) and response regulator (Reg), were investigated, whose overexpression led to great advantages of butenyl-spinosyn biosynthesis. In this way, we successfully discovered three key genes that obviously optimize the biosynthesis of butenyl-spinosyn. Gene cluster simplification performed in conjunction with multiomics analysis is of great practical significance for screening dominant chassis strains and optimizing secondary metabolism. This work provided an idea about screening key factors and efficient construction of production strains.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Familia de Multigenes / Naftoquinonas / Saccharopolyspora / Eliminación de Gen Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Synth Biol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Familia de Multigenes / Naftoquinonas / Saccharopolyspora / Eliminación de Gen Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Synth Biol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos