Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae
Abstract To achieve high efficiency in microbial cell factories, it is crucial to redesign central carbon fluxes to ensure an adequate supply of precursors for producing high-value compounds. In this study, we employed a multi-omics approach to rearrange the central carbon flux of the pyruvate dehyd...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-10-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07103-7 |
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| author | Cairong Lei Xiaopeng Guo Miaomiao Zhang Xiang Zhou Nan Ding Junle Ren Meihan Liu Chenglin Jia Yajuan Wang Jingru Zhao Ziyi Dong Dong Lu |
| author_facet | Cairong Lei Xiaopeng Guo Miaomiao Zhang Xiang Zhou Nan Ding Junle Ren Meihan Liu Chenglin Jia Yajuan Wang Jingru Zhao Ziyi Dong Dong Lu |
| author_sort | Cairong Lei |
| collection | DOAJ |
| description | Abstract To achieve high efficiency in microbial cell factories, it is crucial to redesign central carbon fluxes to ensure an adequate supply of precursors for producing high-value compounds. In this study, we employed a multi-omics approach to rearrange the central carbon flux of the pyruvate dehydrogenase (PDH) bypass, thereby enhancing the supply of intermediate precursors, specifically acetyl-CoA. This enhancement aimed to improve the biosynthesis of acetyl-CoA-derived compounds, such as terpenoids and fatty acid-derived molecules, in Saccharomyces cerevisiae. Through transcriptomic and lipidomic analyses, we identified ALD4 as a key regulatory gene influencing lipid metabolism. Genetic validation demonstrated that overexpression of the mitochondrial acetaldehyde dehydrogenase (ALDH) gene ALD4 resulted in a 20.1% increase in lipid production. This study provides theoretical support for optimising the performance of S. cerevisiae as a “cell factory” for the production of commercial compounds. |
| format | Article |
| id | doaj-art-fb0b0403461743e59ea57321560519cb |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-fb0b0403461743e59ea57321560519cb2025-08-20T02:11:54ZengNature PortfolioCommunications Biology2399-36422024-10-017111310.1038/s42003-024-07103-7Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiaeCairong Lei0Xiaopeng Guo1Miaomiao Zhang2Xiang Zhou3Nan Ding4Junle Ren5Meihan Liu6Chenglin Jia7Yajuan Wang8Jingru Zhao9Ziyi Dong10Dong Lu11Institute of Modern Physics, Chinese Academy of SciencesSchool of Life Science and Engineering, Lanzhou University of TechnologyInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesInstitute of Modern Physics, Chinese Academy of SciencesAbstract To achieve high efficiency in microbial cell factories, it is crucial to redesign central carbon fluxes to ensure an adequate supply of precursors for producing high-value compounds. In this study, we employed a multi-omics approach to rearrange the central carbon flux of the pyruvate dehydrogenase (PDH) bypass, thereby enhancing the supply of intermediate precursors, specifically acetyl-CoA. This enhancement aimed to improve the biosynthesis of acetyl-CoA-derived compounds, such as terpenoids and fatty acid-derived molecules, in Saccharomyces cerevisiae. Through transcriptomic and lipidomic analyses, we identified ALD4 as a key regulatory gene influencing lipid metabolism. Genetic validation demonstrated that overexpression of the mitochondrial acetaldehyde dehydrogenase (ALDH) gene ALD4 resulted in a 20.1% increase in lipid production. This study provides theoretical support for optimising the performance of S. cerevisiae as a “cell factory” for the production of commercial compounds.https://doi.org/10.1038/s42003-024-07103-7 |
| spellingShingle | Cairong Lei Xiaopeng Guo Miaomiao Zhang Xiang Zhou Nan Ding Junle Ren Meihan Liu Chenglin Jia Yajuan Wang Jingru Zhao Ziyi Dong Dong Lu Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae Communications Biology |
| title | Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae |
| title_full | Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae |
| title_fullStr | Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae |
| title_full_unstemmed | Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae |
| title_short | Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae |
| title_sort | regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in saccharomyces cerevisiae |
| url | https://doi.org/10.1038/s42003-024-07103-7 |
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