Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast
Abstract CO2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate tha...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45557-9 |
| _version_ | 1827326964789149696 |
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| author | Ning Qin Lingyun Li Xiaozhen Wan Xu Ji Yu Chen Chaokun Li Ping Liu Yijie Zhang Weijie Yang Junfeng Jiang Jianye Xia Shuobo Shi Tianwei Tan Jens Nielsen Yun Chen Zihe Liu |
| author_facet | Ning Qin Lingyun Li Xiaozhen Wan Xu Ji Yu Chen Chaokun Li Ping Liu Yijie Zhang Weijie Yang Junfeng Jiang Jianye Xia Shuobo Shi Tianwei Tan Jens Nielsen Yun Chen Zihe Liu |
| author_sort | Ning Qin |
| collection | DOAJ |
| description | Abstract CO2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate that the provision of bicarbonate, formed from CO2, restricts previous attempts for high yield production of 3-HP. We thus develop multiple strategies for bicarbonate uptake, including the identification of Sul1 as a potential bicarbonate transporter, domain swapping of malonyl-CoA reductase, identification of Esbp6 as a potential 3-HP exporter, and deletion of Uga1 to prevent 3-HP degradation. The combined rational engineering increases 3-HP production from 0.14 g/L to 11.25 g/L in shake flask using 20 g/L glucose, approaching the maximum theoretical yield with concurrent biomass formation. The engineered yeast forms the basis for commercialization of bio-acrylic acid, while our CO2 fixation strategies pave the way for CO2 being used as the sole carbon source. |
| first_indexed | 2024-03-07T14:53:06Z |
| format | Article |
| id | doaj.art-fea355dc51f14720b2ca021b978cd4d4 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:53:06Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-fea355dc51f14720b2ca021b978cd4d42024-03-05T19:35:25ZengNature PortfolioNature Communications2041-17232024-02-0115111510.1038/s41467-024-45557-9Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeastNing Qin0Lingyun Li1Xiaozhen Wan2Xu Ji3Yu Chen4Chaokun Li5Ping Liu6Yijie Zhang7Weijie Yang8Junfeng Jiang9Jianye Xia10Shuobo Shi11Tianwei Tan12Jens Nielsen13Yun Chen14Zihe Liu15College of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyKey Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesStem Cells and Metabolism Research Program, Faculty of Medicine, University of HelsinkiThe State Key Laboratory of Chemical Resource Engineering, College of Chemical Engineering, Beijing University of Chemical TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyDepartment of Life Sciences, Chalmers University of TechnologyCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical TechnologyAbstract CO2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate that the provision of bicarbonate, formed from CO2, restricts previous attempts for high yield production of 3-HP. We thus develop multiple strategies for bicarbonate uptake, including the identification of Sul1 as a potential bicarbonate transporter, domain swapping of malonyl-CoA reductase, identification of Esbp6 as a potential 3-HP exporter, and deletion of Uga1 to prevent 3-HP degradation. The combined rational engineering increases 3-HP production from 0.14 g/L to 11.25 g/L in shake flask using 20 g/L glucose, approaching the maximum theoretical yield with concurrent biomass formation. The engineered yeast forms the basis for commercialization of bio-acrylic acid, while our CO2 fixation strategies pave the way for CO2 being used as the sole carbon source.https://doi.org/10.1038/s41467-024-45557-9 |
| spellingShingle | Ning Qin Lingyun Li Xiaozhen Wan Xu Ji Yu Chen Chaokun Li Ping Liu Yijie Zhang Weijie Yang Junfeng Jiang Jianye Xia Shuobo Shi Tianwei Tan Jens Nielsen Yun Chen Zihe Liu Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast Nature Communications |
| title | Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast |
| title_full | Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast |
| title_fullStr | Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast |
| title_full_unstemmed | Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast |
| title_short | Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast |
| title_sort | increased co2 fixation enables high carbon yield production of 3 hydroxypropionic acid in yeast |
| url | https://doi.org/10.1038/s41467-024-45557-9 |
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