High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering
4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Zhang, Chenglin [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018transfer abstract |
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| Schlagwörter: |
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| Umfang: |
12 |
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| Übergeordnetes Werk: |
Enthalten in: Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery - Gao, Mengyao ELSEVIER, 2014transfer abstract, Orlando, Fla |
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| Übergeordnetes Werk: |
volume:49 ; year:2018 ; pages:287-298 ; extent:12 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.ymben.2018.09.008 |
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ELV044437609 |
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| 520 | |a 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. | ||
| 520 | |a 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. | ||
| 650 | 7 | |a Corynebacterium glutamicum |2 Elsevier | |
| 650 | 7 | |a 4-Hydroxyisoleucine fermentation |2 Elsevier | |
| 650 | 7 | |a Dynamic modulation |2 Elsevier | |
| 650 | 7 | |a Metabolic engineering |2 Elsevier | |
| 700 | 1 | |a Li, Yanjun |4 oth | |
| 700 | 1 | |a Ma, Jie |4 oth | |
| 700 | 1 | |a Liu, Yuan |4 oth | |
| 700 | 1 | |a He, Jilong |4 oth | |
| 700 | 1 | |a Li, Yingzi |4 oth | |
| 700 | 1 | |a Zhu, Fuzhou |4 oth | |
| 700 | 1 | |a Meng, Jing |4 oth | |
| 700 | 1 | |a Zhan, Junjie |4 oth | |
| 700 | 1 | |a Li, Zhixiang |4 oth | |
| 700 | 1 | |a Zhao, Lei |4 oth | |
| 700 | 1 | |a Ma, Qian |4 oth | |
| 700 | 1 | |a Fan, Xiaoguang |4 oth | |
| 700 | 1 | |a Xu, Qingyang |4 oth | |
| 700 | 1 | |a Xie, Xixian |4 oth | |
| 700 | 1 | |a Chen, Ning |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Academic Press |a Gao, Mengyao ELSEVIER |t Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery |d 2014transfer abstract |g Orlando, Fla |w (DE-627)ELV012555568 |
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10.1016/j.ymben.2018.09.008 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001327.pica (DE-627)ELV044437609 (ELSEVIER)S1096-7176(18)30239-8 DE-627 ger DE-627 rakwb eng 540 VZ 610 VZ 44.00 bkl Zhang, Chenglin verfasserin aut High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering 2018transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. Corynebacterium glutamicum Elsevier 4-Hydroxyisoleucine fermentation Elsevier Dynamic modulation Elsevier Metabolic engineering Elsevier Li, Yanjun oth Ma, Jie oth Liu, Yuan oth He, Jilong oth Li, Yingzi oth Zhu, Fuzhou oth Meng, Jing oth Zhan, Junjie oth Li, Zhixiang oth Zhao, Lei oth Ma, Qian oth Fan, Xiaoguang oth Xu, Qingyang oth Xie, Xixian oth Chen, Ning oth Enthalten in Academic Press Gao, Mengyao ELSEVIER Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery 2014transfer abstract Orlando, Fla (DE-627)ELV012555568 volume:49 year:2018 pages:287-298 extent:12 https://doi.org/10.1016/j.ymben.2018.09.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_40 GBV_ILN_70 44.00 Medizin: Allgemeines VZ AR 49 2018 287-298 12 |
| spelling |
10.1016/j.ymben.2018.09.008 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001327.pica (DE-627)ELV044437609 (ELSEVIER)S1096-7176(18)30239-8 DE-627 ger DE-627 rakwb eng 540 VZ 610 VZ 44.00 bkl Zhang, Chenglin verfasserin aut High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering 2018transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. Corynebacterium glutamicum Elsevier 4-Hydroxyisoleucine fermentation Elsevier Dynamic modulation Elsevier Metabolic engineering Elsevier Li, Yanjun oth Ma, Jie oth Liu, Yuan oth He, Jilong oth Li, Yingzi oth Zhu, Fuzhou oth Meng, Jing oth Zhan, Junjie oth Li, Zhixiang oth Zhao, Lei oth Ma, Qian oth Fan, Xiaoguang oth Xu, Qingyang oth Xie, Xixian oth Chen, Ning oth Enthalten in Academic Press Gao, Mengyao ELSEVIER Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery 2014transfer abstract Orlando, Fla (DE-627)ELV012555568 volume:49 year:2018 pages:287-298 extent:12 https://doi.org/10.1016/j.ymben.2018.09.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_40 GBV_ILN_70 44.00 Medizin: Allgemeines VZ AR 49 2018 287-298 12 |
| allfields_unstemmed |
10.1016/j.ymben.2018.09.008 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001327.pica (DE-627)ELV044437609 (ELSEVIER)S1096-7176(18)30239-8 DE-627 ger DE-627 rakwb eng 540 VZ 610 VZ 44.00 bkl Zhang, Chenglin verfasserin aut High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering 2018transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. Corynebacterium glutamicum Elsevier 4-Hydroxyisoleucine fermentation Elsevier Dynamic modulation Elsevier Metabolic engineering Elsevier Li, Yanjun oth Ma, Jie oth Liu, Yuan oth He, Jilong oth Li, Yingzi oth Zhu, Fuzhou oth Meng, Jing oth Zhan, Junjie oth Li, Zhixiang oth Zhao, Lei oth Ma, Qian oth Fan, Xiaoguang oth Xu, Qingyang oth Xie, Xixian oth Chen, Ning oth Enthalten in Academic Press Gao, Mengyao ELSEVIER Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery 2014transfer abstract Orlando, Fla (DE-627)ELV012555568 volume:49 year:2018 pages:287-298 extent:12 https://doi.org/10.1016/j.ymben.2018.09.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_40 GBV_ILN_70 44.00 Medizin: Allgemeines VZ AR 49 2018 287-298 12 |
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10.1016/j.ymben.2018.09.008 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001327.pica (DE-627)ELV044437609 (ELSEVIER)S1096-7176(18)30239-8 DE-627 ger DE-627 rakwb eng 540 VZ 610 VZ 44.00 bkl Zhang, Chenglin verfasserin aut High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering 2018transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. Corynebacterium glutamicum Elsevier 4-Hydroxyisoleucine fermentation Elsevier Dynamic modulation Elsevier Metabolic engineering Elsevier Li, Yanjun oth Ma, Jie oth Liu, Yuan oth He, Jilong oth Li, Yingzi oth Zhu, Fuzhou oth Meng, Jing oth Zhan, Junjie oth Li, Zhixiang oth Zhao, Lei oth Ma, Qian oth Fan, Xiaoguang oth Xu, Qingyang oth Xie, Xixian oth Chen, Ning oth Enthalten in Academic Press Gao, Mengyao ELSEVIER Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery 2014transfer abstract Orlando, Fla (DE-627)ELV012555568 volume:49 year:2018 pages:287-298 extent:12 https://doi.org/10.1016/j.ymben.2018.09.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_40 GBV_ILN_70 44.00 Medizin: Allgemeines VZ AR 49 2018 287-298 12 |
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10.1016/j.ymben.2018.09.008 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001327.pica (DE-627)ELV044437609 (ELSEVIER)S1096-7176(18)30239-8 DE-627 ger DE-627 rakwb eng 540 VZ 610 VZ 44.00 bkl Zhang, Chenglin verfasserin aut High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering 2018transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. Corynebacterium glutamicum Elsevier 4-Hydroxyisoleucine fermentation Elsevier Dynamic modulation Elsevier Metabolic engineering Elsevier Li, Yanjun oth Ma, Jie oth Liu, Yuan oth He, Jilong oth Li, Yingzi oth Zhu, Fuzhou oth Meng, Jing oth Zhan, Junjie oth Li, Zhixiang oth Zhao, Lei oth Ma, Qian oth Fan, Xiaoguang oth Xu, Qingyang oth Xie, Xixian oth Chen, Ning oth Enthalten in Academic Press Gao, Mengyao ELSEVIER Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery 2014transfer abstract Orlando, Fla (DE-627)ELV012555568 volume:49 year:2018 pages:287-298 extent:12 https://doi.org/10.1016/j.ymben.2018.09.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_40 GBV_ILN_70 44.00 Medizin: Allgemeines VZ AR 49 2018 287-298 12 |
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High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering |
| abstract |
4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. |
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4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. |
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4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. |
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High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering |
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This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Corynebacterium glutamicum</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">4-Hydroxyisoleucine fermentation</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Dynamic modulation</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Metabolic engineering</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Li, Yanjun</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ma, Jie</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liu, Yuan</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">He, Jilong</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Li, Yingzi</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhu, Fuzhou</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Meng, Jing</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhan, Junjie</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Li, Zhixiang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhao, Lei</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ma, Qian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fan, Xiaoguang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xu, Qingyang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xie, Xixian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Ning</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Academic Press</subfield><subfield code="a">Gao, Mengyao ELSEVIER</subfield><subfield code="t">Inhibition on polysulfides dissolve during the discharge-charge by using fish-scale-based porous carbon for lithium-sulfur battery</subfield><subfield code="d">2014transfer abstract</subfield><subfield code="g">Orlando, Fla</subfield><subfield code="w">(DE-627)ELV012555568</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:49</subfield><subfield code="g">year:2018</subfield><subfield code="g">pages:287-298</subfield><subfield code="g">extent:12</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ymben.2018.09.008</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.00</subfield><subfield code="j">Medizin: Allgemeines</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">49</subfield><subfield code="j">2018</subfield><subfield code="h">287-298</subfield><subfield code="g">12</subfield></datafield></record></collection>
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