Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism
Abstract Microbial synthesis of chemicals using renewable feedstocks has gained interest due to its sustainability. The class of β,γ-diols has unique chemical and physical properties, making them valuable for diverse applications. Here, we report a biosynthetic platform in Escherichia coli for the s...
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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/s41467-025-59753-8 |
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| _version_ | 1849309770623746048 |
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| author | Peiling Wu Haofeng Chen Yueyang Chen Yang Zhang Jifeng Yuan |
| author_facet | Peiling Wu Haofeng Chen Yueyang Chen Yang Zhang Jifeng Yuan |
| author_sort | Peiling Wu |
| collection | DOAJ |
| description | Abstract Microbial synthesis of chemicals using renewable feedstocks has gained interest due to its sustainability. The class of β,γ-diols has unique chemical and physical properties, making them valuable for diverse applications. Here, we report a biosynthetic platform in Escherichia coli for the synthesis of branched-chain β,γ-diols from renewable feedstocks. Firstly, we identify an acetohydroxyacid synthase from Saccharomyces cerevisiae to catalyze the condensation of branched-chain aldehydes with pyruvate, forming α-hydroxyketones. Next, de novo production of branched-chain β,γ-diols (4-methylpentane-2,3-diol, 5-methylhexane-2,3-diol and 4-methylhexane-2,3-diol) is realized from branched-chain amino acids (BCAA) metabolism. After systematic optimization of the BCAA pathway, we have achieved high-specificity production of 4-methylpentane-2,3-diol from glucose, achieving 129.8 mM (15.3 g/L) 4-methylpentane-2,3-diol with 72% of the theoretical yield. In summary, our work demonstrates the synthesis of structurally diverse branched-chain β,γ-diols, highlighting its potential as a versatile carbon elongation system for other β,γ-diol productions. |
| format | Article |
| id | doaj-art-f033a28cee0a431fbcbf629e9c8d58f5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f033a28cee0a431fbcbf629e9c8d58f52025-08-20T03:53:58ZengNature PortfolioNature Communications2041-17232025-05-0116111210.1038/s41467-025-59753-8Microbial synthesis of branched-chain β,γ-diols from amino acid metabolismPeiling Wu0Haofeng Chen1Yueyang Chen2Yang Zhang3Jifeng Yuan4State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityAbstract Microbial synthesis of chemicals using renewable feedstocks has gained interest due to its sustainability. The class of β,γ-diols has unique chemical and physical properties, making them valuable for diverse applications. Here, we report a biosynthetic platform in Escherichia coli for the synthesis of branched-chain β,γ-diols from renewable feedstocks. Firstly, we identify an acetohydroxyacid synthase from Saccharomyces cerevisiae to catalyze the condensation of branched-chain aldehydes with pyruvate, forming α-hydroxyketones. Next, de novo production of branched-chain β,γ-diols (4-methylpentane-2,3-diol, 5-methylhexane-2,3-diol and 4-methylhexane-2,3-diol) is realized from branched-chain amino acids (BCAA) metabolism. After systematic optimization of the BCAA pathway, we have achieved high-specificity production of 4-methylpentane-2,3-diol from glucose, achieving 129.8 mM (15.3 g/L) 4-methylpentane-2,3-diol with 72% of the theoretical yield. In summary, our work demonstrates the synthesis of structurally diverse branched-chain β,γ-diols, highlighting its potential as a versatile carbon elongation system for other β,γ-diol productions.https://doi.org/10.1038/s41467-025-59753-8 |
| spellingShingle | Peiling Wu Haofeng Chen Yueyang Chen Yang Zhang Jifeng Yuan Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism Nature Communications |
| title | Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism |
| title_full | Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism |
| title_fullStr | Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism |
| title_full_unstemmed | Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism |
| title_short | Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism |
| title_sort | microbial synthesis of branched chain β γ diols from amino acid metabolism |
| url | https://doi.org/10.1038/s41467-025-59753-8 |
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