Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiae
Lavandulol, the primary chemical constituent of lavender essential oil, is an irregular monoterpene present in Lavandula angustifolia. It has been employed in the spice and cosmetic industries owing to its pleasing aromatic properties. In addition, its efficacy as an inhibitor of insect mating behav...
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KeAi Communications Co., Ltd.
2025-12-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X25000869 |
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| author | Shengxin Nie Ruiqi Chen Mingyue Ge Yue Qu Xiaofeng Liu Chaofeng Ruan Xiaoguang Yan Jianjun Qiao |
| author_facet | Shengxin Nie Ruiqi Chen Mingyue Ge Yue Qu Xiaofeng Liu Chaofeng Ruan Xiaoguang Yan Jianjun Qiao |
| author_sort | Shengxin Nie |
| collection | DOAJ |
| description | Lavandulol, the primary chemical constituent of lavender essential oil, is an irregular monoterpene present in Lavandula angustifolia. It has been employed in the spice and cosmetic industries owing to its pleasing aromatic properties. In addition, its efficacy as an inhibitor of insect mating behaviour has led to incorporation within synthetic pheromone formulations. With the development of synthetic biology, more terpenoids are synthesized utilizing microorganisms. In this study, lavandulol was biosynthesized in Saccharomyces cerevisiae for the first time. An initial screening of lavandulyl diphosphate candidates was performed to identify enzymes compatible with heterologous expression in yeast. To increase the supply of DMAPP, the key enzymes of the MVA pathway, IDI1 and tHMG, as well as IDI1, ERG12, and ERG8 were overexpressed. Furthermore, the metabolic flow loss of acetyl-CoA and DMAPP was also reduced by deleting the genes of MLS1 and CIT2, as well as replacing the ERG20 promoter. Through the modification of lavandulyl diphosphate synthase, the flask titer was increased to 136.68 mg/L. Finally, the highest reported level of lavandulol production (308.92 mg/L) in S. cerevisiae was achieved by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this is the first report of heterologous biosynthesis of lavandulol in S. cerevisiae. |
| format | Article |
| id | doaj-art-ce2ed2dd3825402db97d7bc47d351f45 |
| institution | DOAJ |
| issn | 2405-805X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Synthetic and Systems Biotechnology |
| spelling | doaj-art-ce2ed2dd3825402db97d7bc47d351f452025-08-20T03:16:02ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2025-12-011041267127410.1016/j.synbio.2025.06.001Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiaeShengxin Nie0Ruiqi Chen1Mingyue Ge2Yue Qu3Xiaofeng Liu4Chaofeng Ruan5Xiaoguang Yan6Jianjun Qiao7State Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, ChinaState Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, ChinaState Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, ChinaState Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, ChinaState Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, China; Zhejiang Institute of Tianjin University (Shaoxing), Shaoxing, 312300, ChinaState Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, China; Zhejiang Institute of Tianjin University (Shaoxing), Shaoxing, 312300, ChinaState Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, China; Corresponding author. School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, China.State Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, 300072, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, 300072, China; Corresponding author. School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, China.Lavandulol, the primary chemical constituent of lavender essential oil, is an irregular monoterpene present in Lavandula angustifolia. It has been employed in the spice and cosmetic industries owing to its pleasing aromatic properties. In addition, its efficacy as an inhibitor of insect mating behaviour has led to incorporation within synthetic pheromone formulations. With the development of synthetic biology, more terpenoids are synthesized utilizing microorganisms. In this study, lavandulol was biosynthesized in Saccharomyces cerevisiae for the first time. An initial screening of lavandulyl diphosphate candidates was performed to identify enzymes compatible with heterologous expression in yeast. To increase the supply of DMAPP, the key enzymes of the MVA pathway, IDI1 and tHMG, as well as IDI1, ERG12, and ERG8 were overexpressed. Furthermore, the metabolic flow loss of acetyl-CoA and DMAPP was also reduced by deleting the genes of MLS1 and CIT2, as well as replacing the ERG20 promoter. Through the modification of lavandulyl diphosphate synthase, the flask titer was increased to 136.68 mg/L. Finally, the highest reported level of lavandulol production (308.92 mg/L) in S. cerevisiae was achieved by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this is the first report of heterologous biosynthesis of lavandulol in S. cerevisiae.http://www.sciencedirect.com/science/article/pii/S2405805X25000869LavandulolIrregular monoterpeneHeterologous biosynthesisSaccharomyces cerevisiae |
| spellingShingle | Shengxin Nie Ruiqi Chen Mingyue Ge Yue Qu Xiaofeng Liu Chaofeng Ruan Xiaoguang Yan Jianjun Qiao Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiae Synthetic and Systems Biotechnology Lavandulol Irregular monoterpene Heterologous biosynthesis Saccharomyces cerevisiae |
| title | Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiae |
| title_full | Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiae |
| title_fullStr | Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiae |
| title_full_unstemmed | Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiae |
| title_short | Biosynthesis of irregular monoterpene lavandulol in Saccharomyces cerevisiae |
| title_sort | biosynthesis of irregular monoterpene lavandulol in saccharomyces cerevisiae |
| topic | Lavandulol Irregular monoterpene Heterologous biosynthesis Saccharomyces cerevisiae |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X25000869 |
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