Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi

Artemisia argyi H. Lév. & Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of A. argyi, including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterp...

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Main Authors: Zhengping Li, Yuhong Gan, Changyu Gou, Qiongyu Ye, Yang Wu, Yuhong Wu, Tingxing Yang, Baolian Fan, Aijia Ji, Qi Shen, Lixin Duan
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-03-01
Series:Synthetic and Systems Biotechnology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405805X24001248
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author Zhengping Li
Yuhong Gan
Changyu Gou
Qiongyu Ye
Yang Wu
Yuhong Wu
Tingxing Yang
Baolian Fan
Aijia Ji
Qi Shen
Lixin Duan
author_facet Zhengping Li
Yuhong Gan
Changyu Gou
Qiongyu Ye
Yang Wu
Yuhong Wu
Tingxing Yang
Baolian Fan
Aijia Ji
Qi Shen
Lixin Duan
author_sort Zhengping Li
collection DOAJ
description Artemisia argyi H. Lév. & Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of A. argyi, including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterpenoids in A. argyi remains underexplored. In this study, we identified four β-caryophyllene synthases from A. argyi. A high-yield β-caryophyllene engineered Saccharomyces cerevisiae cell factory has been built in this study. By fusing ERG20 and AarTPS88 with a flexible linker (GGGS)2 and enhancing metabolic flux in the MVA pathway (HIF-1, tHMGR, and UPC2-1), we achieved a titer of β-caryophyllene reached 15.6 g/L by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this represents the highest reported titer of β-caryophyllene in yeast to date. This study provides a valuable tool for the industrial-scale production of β-caryophyllene.
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issn 2405-805X
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publishDate 2025-03-01
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spelling doaj-art-83745ce9c0b149918841b2c8c9e3d1522025-08-20T03:13:21ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2025-03-0110115816410.1016/j.synbio.2024.09.005Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyiZhengping Li0Yuhong Gan1Changyu Gou2Qiongyu Ye3Yang Wu4Yuhong Wu5Tingxing Yang6Baolian Fan7Aijia Ji8Qi Shen9Lixin Duan10Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaInstitute of Medical Plant Physiology and Ecology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaGuangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China; Corresponding author.Artemisia argyi H. Lév. & Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of A. argyi, including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterpenoids in A. argyi remains underexplored. In this study, we identified four β-caryophyllene synthases from A. argyi. A high-yield β-caryophyllene engineered Saccharomyces cerevisiae cell factory has been built in this study. By fusing ERG20 and AarTPS88 with a flexible linker (GGGS)2 and enhancing metabolic flux in the MVA pathway (HIF-1, tHMGR, and UPC2-1), we achieved a titer of β-caryophyllene reached 15.6 g/L by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this represents the highest reported titer of β-caryophyllene in yeast to date. This study provides a valuable tool for the industrial-scale production of β-caryophyllene.http://www.sciencedirect.com/science/article/pii/S2405805X24001248Artemisia argyiβ-caryophylleneβ-caryophyllene synthaseBiosynthesisSaccharomyces cerevisiae
spellingShingle Zhengping Li
Yuhong Gan
Changyu Gou
Qiongyu Ye
Yang Wu
Yuhong Wu
Tingxing Yang
Baolian Fan
Aijia Ji
Qi Shen
Lixin Duan
Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi
Synthetic and Systems Biotechnology
Artemisia argyi
β-caryophyllene
β-caryophyllene synthase
Biosynthesis
Saccharomyces cerevisiae
title Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi
title_full Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi
title_fullStr Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi
title_full_unstemmed Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi
title_short Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi
title_sort efficient biosynthesis of β caryophyllene in saccharomyces cerevisiae by β caryophyllene synthase from artemisia argyi
topic Artemisia argyi
β-caryophyllene
β-caryophyllene synthase
Biosynthesis
Saccharomyces cerevisiae
url http://www.sciencedirect.com/science/article/pii/S2405805X24001248
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