Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-Menthol
Menthol, a high-value commodity monoterpenoid chemical, holds an important market share commercially because of its distinct functions. The menthol on the market mainly originates from plant extraction, which is facing challenges such as the seasonal fluctuations and long growth cycle of plants. The...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/8/9/982 |
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| author | Xueqin Lv Xuan Zhou Jun Ma Mengrui Tao Yanfeng Liu Jianghua Li Guocheng Du Long Liu |
| author_facet | Xueqin Lv Xuan Zhou Jun Ma Mengrui Tao Yanfeng Liu Jianghua Li Guocheng Du Long Liu |
| author_sort | Xueqin Lv |
| collection | DOAJ |
| description | Menthol, a high-value commodity monoterpenoid chemical, holds an important market share commercially because of its distinct functions. The menthol on the market mainly originates from plant extraction, which is facing challenges such as the seasonal fluctuations and long growth cycle of plants. Therefore, this study attempted to realize the <i>de novo</i> synthesis of menthol through microbial fermentation. First, through heterologous expression and subcellular localization observation, a synthetic route from glucose to (−)-menthol was successfully designed and constructed in <i>Saccharomyces cerevisiae</i>. Then, the mevalonate (MVA) pathway was enhanced, and the expression of farnesyl diphosphate synthase (<i>ERG20</i>) was dynamically regulated to improve the synthesis of D-limonene, a key precursor of (−)-menthol. Shake flask fermentation results showed that the D-limonene titer of the recombinant strain reached 459.59 mg/L. Next, the synthesis pathway from D-limonene to (−)-menthol was strengthened, and the fermentation medium was optimized. The (−)-menthol titer of 6.28 mg/L was obtained, implying that the <i>de novo</i> synthesis of menthol was successfully realized for the first time. This study provides a good foundation for the synthesis of menthol through microbial fermentation. |
| first_indexed | 2024-03-09T23:30:40Z |
| format | Article |
| id | doaj.art-db37bdebb52e4a76a7b042927a76a550 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T23:30:40Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-db37bdebb52e4a76a7b042927a76a5502023-11-23T17:10:18ZengMDPI AGJournal of Fungi2309-608X2022-09-018998210.3390/jof8090982Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-MentholXueqin Lv0Xuan Zhou1Jun Ma2Mengrui Tao3Yanfeng Liu4Jianghua Li5Guocheng Du6Long Liu7Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, ChinaKey Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, ChinaScience Center for Future Foods, Jiangnan University, Wuxi 214122, ChinaScience Center for Future Foods, Jiangnan University, Wuxi 214122, ChinaKey Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, ChinaKey Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, ChinaKey Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, ChinaKey Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, ChinaMenthol, a high-value commodity monoterpenoid chemical, holds an important market share commercially because of its distinct functions. The menthol on the market mainly originates from plant extraction, which is facing challenges such as the seasonal fluctuations and long growth cycle of plants. Therefore, this study attempted to realize the <i>de novo</i> synthesis of menthol through microbial fermentation. First, through heterologous expression and subcellular localization observation, a synthetic route from glucose to (−)-menthol was successfully designed and constructed in <i>Saccharomyces cerevisiae</i>. Then, the mevalonate (MVA) pathway was enhanced, and the expression of farnesyl diphosphate synthase (<i>ERG20</i>) was dynamically regulated to improve the synthesis of D-limonene, a key precursor of (−)-menthol. Shake flask fermentation results showed that the D-limonene titer of the recombinant strain reached 459.59 mg/L. Next, the synthesis pathway from D-limonene to (−)-menthol was strengthened, and the fermentation medium was optimized. The (−)-menthol titer of 6.28 mg/L was obtained, implying that the <i>de novo</i> synthesis of menthol was successfully realized for the first time. This study provides a good foundation for the synthesis of menthol through microbial fermentation.https://www.mdpi.com/2309-608X/8/9/982menthol<i>De Novo</i> synthesisD-limonene<i>Saccharomyces cerevisiae</i> |
| spellingShingle | Xueqin Lv Xuan Zhou Jun Ma Mengrui Tao Yanfeng Liu Jianghua Li Guocheng Du Long Liu Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-Menthol Journal of Fungi menthol <i>De Novo</i> synthesis D-limonene <i>Saccharomyces cerevisiae</i> |
| title | Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-Menthol |
| title_full | Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-Menthol |
| title_fullStr | Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-Menthol |
| title_full_unstemmed | Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-Menthol |
| title_short | Engineered <i>Saccharomyces cerevisiae</i> for the <i>De Novo</i> Biosynthesis of (−)-Menthol |
| title_sort | engineered i saccharomyces cerevisiae i for the i de novo i biosynthesis of menthol |
| topic | menthol <i>De Novo</i> synthesis D-limonene <i>Saccharomyces cerevisiae</i> |
| url | https://www.mdpi.com/2309-608X/8/9/982 |
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