Modular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiae
Abstract The tightly regulated central carbon metabolism in Saccharomyces cerevisiae, intricately linked to carbon sources utilized, poses a significant challenge to engineering efforts aimed at increasing the flux through its different pathways. Here, we present a modular deregulation strategy that...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59966-x |
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| author | Xiaowei Li Yanyan Wang Xin Chen Leon Eisentraut Chunjun Zhan Jens Nielsen Yun Chen |
| author_facet | Xiaowei Li Yanyan Wang Xin Chen Leon Eisentraut Chunjun Zhan Jens Nielsen Yun Chen |
| author_sort | Xiaowei Li |
| collection | DOAJ |
| description | Abstract The tightly regulated central carbon metabolism in Saccharomyces cerevisiae, intricately linked to carbon sources utilized, poses a significant challenge to engineering efforts aimed at increasing the flux through its different pathways. Here, we present a modular deregulation strategy that enables high conversion rates of xylose through the central carbon metabolism. Specifically, employing a multifaceted approach encompassing five different engineering strategies—promoter engineering, transcription factor manipulation, biosensor construction, introduction of heterologous enzymes, and expression of mutant enzymes we engineer different modules of the central carbon metabolism at both the genetic and enzymatic levels. This leads to an enhanced conversion rate of xylose into acetyl-CoA-derived products, with 3-hydroxypropionic acid (3–HP) serving as a representative case in this study. By implementing a combination of these approaches, the developed yeast strain demonstrates a remarkable enhancement in 3–HP productivity, achieving a 4.7–fold increase when compared to our initially optimized 3–HP producing strain grown on xylose as carbon source. These results illustrate that the rational engineering of yeast central metabolism is a viable approach for boosting the metabolic flux towards acetyl–CoA–derived products on a non-glucose carbon source. |
| format | Article |
| id | doaj-art-7a6ecec72e534940bc6424f8927265dd |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7a6ecec72e534940bc6424f8927265dd2025-08-20T02:25:08ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59966-xModular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiaeXiaowei Li0Yanyan Wang1Xin Chen2Leon Eisentraut3Chunjun Zhan4Jens Nielsen5Yun Chen6Tianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesDepartment of Life Sciences, Chalmers University of TechnologyDepartment of Life Sciences, Chalmers University of TechnologyDepartment of Life Sciences, Chalmers University of TechnologyDepartment of Life Sciences, Chalmers University of TechnologyDepartment of Life Sciences, Chalmers University of TechnologyAbstract The tightly regulated central carbon metabolism in Saccharomyces cerevisiae, intricately linked to carbon sources utilized, poses a significant challenge to engineering efforts aimed at increasing the flux through its different pathways. Here, we present a modular deregulation strategy that enables high conversion rates of xylose through the central carbon metabolism. Specifically, employing a multifaceted approach encompassing five different engineering strategies—promoter engineering, transcription factor manipulation, biosensor construction, introduction of heterologous enzymes, and expression of mutant enzymes we engineer different modules of the central carbon metabolism at both the genetic and enzymatic levels. This leads to an enhanced conversion rate of xylose into acetyl-CoA-derived products, with 3-hydroxypropionic acid (3–HP) serving as a representative case in this study. By implementing a combination of these approaches, the developed yeast strain demonstrates a remarkable enhancement in 3–HP productivity, achieving a 4.7–fold increase when compared to our initially optimized 3–HP producing strain grown on xylose as carbon source. These results illustrate that the rational engineering of yeast central metabolism is a viable approach for boosting the metabolic flux towards acetyl–CoA–derived products on a non-glucose carbon source.https://doi.org/10.1038/s41467-025-59966-x |
| spellingShingle | Xiaowei Li Yanyan Wang Xin Chen Leon Eisentraut Chunjun Zhan Jens Nielsen Yun Chen Modular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiae Nature Communications |
| title | Modular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiae |
| title_full | Modular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiae |
| title_fullStr | Modular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiae |
| title_full_unstemmed | Modular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiae |
| title_short | Modular deregulation of central carbon metabolism for efficient xylose utilization in Saccharomyces cerevisiae |
| title_sort | modular deregulation of central carbon metabolism for efficient xylose utilization in saccharomyces cerevisiae |
| url | https://doi.org/10.1038/s41467-025-59966-x |
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