Characterization of a sesquiterpene synthase and a short-chain dehydrogenase in zerumbone biosynthesis and the applications in engineered Saccharomyces cerevisiae
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| Publicat a: | Frontiers in Plant Science vol. 16 (Oct 2025), p. 1635141-1635153 |
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| Autor principal: | |
| Altres autors: | , , , , , , , , , , |
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Frontiers Media SA
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| Accés en línia: | Citation/Abstract Full Text Full Text - PDF |
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| 001 | 3273797852 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 1664-462X | ||
| 024 | 7 | |a 10.3389/fpls.2025.1635141 |2 doi | |
| 035 | |a 3273797852 | ||
| 045 | 2 | |b d20251001 |b d20251031 | |
| 100 | 1 | |a Xu, Mengdie |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China | |
| 245 | 1 | |a Characterization of a sesquiterpene synthase and a short-chain dehydrogenase in zerumbone biosynthesis and the applications in engineered Saccharomyces cerevisiae | |
| 260 | |b Frontiers Media SA |c Oct 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a IntroductionZerumbone is a pharmacologically active sesquiterpenoid with limited availability. This study aims to elucidate its biosynthetic pathway in Curcuma wenyujin by identifying and characterizing the key enzymes responsible for its production.MethodsCandidate genes were selected via transcriptome analysis and phylogenetics. CwTPS8 and CwSDR1 were cloned and functionally characterized using in vitro enzyme assays and heterologous expression in engineered Saccharomyces cerevisiae . Molecular docking and site-directed mutagenesis were applied to investigate the catalytic mechanism of CwTPS8.ResultsCwTPS8 was identified as a multifunctional sesquiterpene synthase that catalyzes the formation of α-humulene (a key zerumbone precursor) and β-caryophyllene as main products, along with several minor sesquiterpenes. Mutagenesis studies identified critical residues (e.g., Thr437, Cys436) that significantly shift product specificity toward α-humulene. CwSDR1 was characterized as a short-chain dehydrogenase that efficiently oxidizes 8-hydroxy-α-humulene to zerumbone. A de novo biosynthetic pathway was reconstructed in yeast, resulting in zerumbone production at 0.50 μg/L.DiscussionThis study expands the genetic toolkit for zerumbone biosynthesis and provides insights into enzyme engineering and metabolic engineering strategies to enhance production. Limitations in precursor supply and catalytic efficiency highlight areas for future optimization. | |
| 653 | |a Transcriptomes | ||
| 653 | |a Biosynthesis | ||
| 653 | |a Software | ||
| 653 | |a Caryophyllene | ||
| 653 | |a Metabolic engineering | ||
| 653 | |a E coli | ||
| 653 | |a Metabolism | ||
| 653 | |a Yeast | ||
| 653 | |a Genes | ||
| 653 | |a Dehydrogenases | ||
| 653 | |a Factories | ||
| 653 | |a Physicochemical properties | ||
| 653 | |a Sesquiterpenes | ||
| 653 | |a Dehydrogenase | ||
| 653 | |a Oxidation | ||
| 653 | |a Molecular docking | ||
| 653 | |a Site-directed mutagenesis | ||
| 653 | |a Cloning | ||
| 653 | |a Zerumbone | ||
| 653 | |a DNA polymerase | ||
| 653 | |a Precursors | ||
| 653 | |a Humulene | ||
| 653 | |a Sesquiterpene synthase | ||
| 653 | |a Enzymes | ||
| 653 | |a Saccharomyces cerevisiae | ||
| 653 | |a Environmental | ||
| 700 | 1 | |a Xia, Yimeng |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China | |
| 700 | 1 | |a Fang, Gaowei |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China | |
| 700 | 1 | |a Li, Tangli |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China | |
| 700 | 1 | |a Ma, Jing |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China | |
| 700 | 1 | |a Li, Dengyu |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China | |
| 700 | 1 | |a Qiuhui Wei |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China, Xinchang Pharmaceutical Factory, Zhejiang Medicine Co., Ltd., Shaoxing, Zhejiang, China | |
| 700 | 1 | |a Tu, Lichan |u Department of Pharmacy, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China | |
| 700 | 1 | |a Yin, Xiaopu |u Xiaopu Yin [AFFILIATION="School of Pharmacy, Hangzhou Normal University, Hangzhou, China, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines | |
| 700 | 1 | |a Engineering Laboratory of Development and Application of Traditional Chinese Medicines | |
| 700 | 1 | |a Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China"] | |
| 700 | 1 | |a Hu, Tianyuan |u School of Pharmacy, Hangzhou Normal University, Hangzhou, China, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China, Xinchang Pharmaceutical Factory, Zhejiang Medicine Co., Ltd., Shaoxing, Zhejiang, China, State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijing, China | |
| 773 | 0 | |t Frontiers in Plant Science |g vol. 16 (Oct 2025), p. 1635141-1635153 | |
| 786 | 0 | |d ProQuest |t Agriculture Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3273797852/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/3273797852/fulltext/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3273797852/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |