Article
Metabolic engineering of sesquiterpene metabolism in yeast
Abstract
Terpenes are structurally diverse compounds that are of interest because of their biological activities and industrial value. These compounds consist of chirally rich hydrocarbon backbones derived from terpene synthases, which are subsequently decorated with hydroxyl substituents catalyzed by terpene hydroxylases. Availability of these compounds is, however, limited by intractable synthetic means and because they are produced in low amounts and as complex mixtures by natural sources. We engineered yeast for sesquiterpene accumulation by introducing genetic modifications that enable the yeast to accumulate high levels of the key intermediate farnesyl diphosphate (FPP). Co‐expression of terpene synthase genes diverted the enlarged FPP pool to greater than 80 mg/L of sesquiterpene. Efficient coupling of terpene production with hydroxylation was also demonstrated by coordinate expression of terpene hydroxylase activity, yielding 50 mg/L each of hydrocarbon and hydroxylated products. These yeast now provide a convenient format for investigating catalytic coupling between terpene synthases and hydroxylases, as well as a platform for the industrial production of high value, single‐entity and stereochemically unique terpenes. Biotechnol. Bioeng. 2007;97: 170–181. © 2006 Wiley Periodicals, Inc.
Citing Literature
Number of times cited: 68
- Ammara Khalid, Hiroshi Takagi, Suresh Panthee, Makoto Muroi, Joe Chappell, Hiroyuki Osada and Shunji Takahashi, Development of a Terpenoid-Production Platform in Streptomyces reveromyceticus SN-593, ACS Synthetic Biology, 6, 12, (2339), (2017).
- Francisco Carrau, Eduardo Boido and Eduardo Dellacassa, Yeast Diversity and Flavor Compounds, Fungal Metabolites, 10.1007/978-3-319-25001-4_32, (569-597), (2017).
- Isak S. Pretorius, Synthetic genome engineering forging new frontiers for wine yeast, Critical Reviews in Biotechnology, 10.1080/07388551.2016.1214945, 37, 1, (112-136), (2016).
- Wei Suong Teo, Yu Chyuan Heng, Binbin Chen, Hui Ling Lee, Niying Chua and Matthew Wook Chang, Synthetic Biology for Biofuels in Saccharomyces cerevisiae, Consequences of Microbial Interactions with Hydrocarbons, Oils, and Lipids: Production of Fuels and Chemicals, 10.1007/978-3-319-31421-1_386-2, (1-22), (2017).
- Thuy T. B. Ly, Alexander Schifrin, Bach Duc Nguyen and Rita Bernhardt, Improvement of a P450-Based Recombinant Escherichia coli Whole-Cell System for the Production of Oxygenated Sesquiterpene Derivatives , Journal of Agricultural and Food Chemistry, 10.1021/acs.jafc.7b00792, 65, 19, (3891-3899), (2017).
- E. F. Semenova, A. I. Shpichka and E. V. Presnyakova, Aromatic and monoterpene alcohol accumulation by Eremothecium ashbyi strains differing in riboflavinogenesis, Applied Biochemistry and Microbiology, 53, 3, (374), (2017).
- Wei Suong Teo, Yu Chyuan Heng, Binbin Chen, Hui Ling Lee, Niying Chua and Matthew Wook Chang, Synthetic Biology for Biofuels in Saccharomyces cerevisiae, Consequences of Microbial Interactions with Hydrocarbons, Oils, and Lipids: Production of Fuels and Chemicals, 10.1007/978-3-319-31421-1_386-1, (1-22), (2017).
- Xia Yang, Komi Nambou, Liujing Wei and Qiang Hua, Heterologous production of α-farnesene in metabolically engineered strains of Yarrowia lipolytica, Bioresource Technology, 216, (1040), (2016).
- Yuxia Sun, Liang Sun, Fei Shang and Guoliang Yan, Enhanced production of β-carotene in recombinant Saccharomyces cerevisiae by inverse metabolic engineering with supplementation of unsaturated fatty acids, Process Biochemistry, 10.1016/j.procbio.2016.02.004, 51, 5, (568-577), (2016).
- Arno Hazekamp, Katerina Tejkalová and Stelios Papadimitriou, Cannabis: From Cultivar to Chemovar II—A Metabolomics Approach to Cannabis Classification, Cannabis and Cannabinoid Research, 1, 1, (202), (2016).
- Tian Ma, Zixin Deng and Tiangang Liu, Microbial production strategies and applications of lycopene and other terpenoids, World Journal of Microbiology and Biotechnology, 32, 1, (2016).
- Xiang Chen, Yuwei Wang, Jia Sun, Jin Wang, Hang Xun and Feng Tang, Cloning, expression and functional characterization of two sesquiterpene synthase genes from moso bamboo (Phyllostachys edulis), Protein Expression and Purification, 120, (1), (2016).
- Lidan Ye, Xiaomei Lv and Hongwei Yu, Engineering microbes for isoprene production, Metabolic Engineering, 10.1016/j.ymben.2016.07.005, 38, (125-138), (2016).
- Mohammad Majdi, Morahem Ashengroph and Mohammad Reza Abdollahi, Sesquiterpene lactone engineering in microbial and plant platforms: parthenolide and artemisinin as case studies, Applied Microbiology and Biotechnology, 100, 3, (1041), (2016).
- A. Bergman and V. Siewers, Metabolic Engineering Strategies to Convert Carbohydrates to Aviation Range Hydrocarbons, Biofuels for Aviation, 10.1016/B978-0-12-804568-8.00007-X, (151-190), (2016).
- P. Gupta and S.C. Phulara, Metabolic engineering for isoprenoid‐based biofuel production, Journal of Applied Microbiology, 119, 3, (605-619), (2015).
- Xun Zhuang and Joe Chappell, Building terpene production platforms in yeast, Biotechnology and Bioengineering, 112, 9, (1854-1864), (2015).
- Cheng Hu and Wenyu Lu, Insight into yeast: A study model of lipid metabolism and terpenoid biosynthesis, Biotechnology and Applied Biochemistry, 62, 3, (323-328), (2014).
- Lloyd W. Sumner, Zhentian Lei, Basil J. Nikolau and Kazuki Saito, Modern plant metabolomics: advanced natural product gene discoveries, improved technologies, and future prospects, Natural Product Reports, 10.1039/C4NP00072B, 32, 2, (212-229), (2015).
- N. Kusaira B. K. Ikram, Xin Zhan, Xi-Wu Pan, Brian C. King and Henrik T. Simonsen, Stable heterologous expression of biologically active terpenoids in green plant cells, Frontiers in Plant Science, 6, (2015).
- Rama Raju Baadhe, Ravichandra Potumarthi, Naveen Kumar Mekala and Vijai K. Gupta, New trends in microbial production of natural complex bioactive isoprenoids, Biotechnology of Bioactive Compounds, (269-282), (2015).
- Godson O. Osuji, Aruna Weerasooriya, Peter A. Y. Ampim, Laura Carson, Paul Johnson, Yoonsung Jung, Eustace Duffus, Sela Woldesenbet, Sanique South, Edna Idan, Dewisha Johnson, Diadrian Clarke, Billy Lawton, Alfred Parks, Ali Fares and Alton Johnson, Molecular Regulation of the Metabolic Pathways of the Medicinal Plants: <i>Phyla dulcis</i>, American Journal of Plant Sciences, 06, 11, (1717), (2015).
- Sarah E. O'Connor, Engineering of Secondary Metabolism, Annual Review of Genetics, 49, 1, (71), (2015).
- Jules Beekwilder, Adèle Houwelingen, Katarina Cankar, Aalt D.J. Dijk, René M. Jong, Geert Stoopen, Harro Bouwmeester, Jihane Achkar, Theo Sonke and Dirk Bosch, Valencene synthase from the heartwood of Nootka cypress (allitropsis nootkatensis) for biotechnological production of valencene, Plant Biotechnology Journal, 12, 2, (174-182), (2013).
- Shiro Suzuki, Takao Koeduka, Akifumi Sugiyama, Kazufumi Yazaki and Toshiaki Umezawa, Microbial production of plant specialized metabolites, Plant Biotechnology, 10.5511/plantbiotechnology.14.1003a, 31, 5, (465-482), (2014).
- Tamara Wriessnegger, Peter Augustin, Matthias Engleder, Erich Leitner, Monika Müller, Iwona Kaluzna, Martin Schürmann, Daniel Mink, Günther Zellnig, Helmut Schwab and Harald Pichler, Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris, Metabolic Engineering, 10.1016/j.ymben.2014.04.001, 24, (18-29), (2014).
- Thomas Brück, Robert Kourist and Bernhard Loll, Production of Macrocyclic Sesqui‐ and Diterpenes in Heterologous Microbial Hosts: A Systems Approach to Harness Nature’s Molecular Diversity, ChemCatChem, 6, 5, (1142-1165), (2014).
- Daniel Barajas, Kai Xu, Isabel Fernández de Castro Martín, Zsuzsanna Sasvari, Federica Brandizzi, Cristina Risco, Peter D. Nagy and Aiming Wang, Co-opted Oxysterol-Binding ORP and VAP Proteins Channel Sterols to RNA Virus Replication Sites via Membrane Contact Sites, PLoS Pathogens, 10, 10, (e1004388), (2014).
- CLAUDIA E. VICKERS, MAREIKE BONGERS, QING LIU, THIERRY DELATTE and HARRO BOUWMEESTER, Metabolic engineering of volatile isoprenoids in plants and microbes, Plant, Cell & Environment, 37, 8, (1753-1775), (2014).
- Zhiqiang Sun, Hailin Meng, Jing Li, Jianfeng Wang, Qian Li, Yong Wang, Yansheng Zhang and Alvaro Galli, Identification of Novel Knockout Targets for Improving Terpenoids Biosynthesis in Saccharomyces cerevisiae, PLoS ONE, 9, 11, (e112615), (2014).
- Nicolaas A Buijs, Verena Siewers and Jens Nielsen, Advanced biofuel production by the yeast Saccharomyces cerevisiae, Current Opinion in Chemical Biology, 17, 3, (480), (2013).
- Tamara Wriessnegger and Harald Pichler, Yeast metabolic engineering – Targeting sterol metabolism and terpenoid formation, Progress in Lipid Research, 10.1016/j.plipres.2013.03.001, 52, 3, (277-293), (2013).
- Manhoi Hur, Alexis Ann Campbell, Marcia Almeida-de-Macedo, Ling Li, Nick Ransom, Adarsh Jose, Matt Crispin, Basil J. Nikolau and Eve Syrkin Wurtele, A global approach to analysis and interpretation of metabolic data for plant natural product discovery, Natural Product Reports, 30, 4, (565), (2013).
- Chaoyou Xue, Yuejiao Duan, Fanglong Zhao and Wenyu Lu, Stepwise increase of spinosad production in Saccharopolyspora spinosa by metabolic engineering, Biochemical Engineering Journal, 72, (90), (2013).
- Stefan Tippmann, Yun Chen, Verena Siewers and Jens Nielsen , From flavors and pharmaceuticals to advanced biofuels: Production of isoprenoids in Saccharomyces cerevisiae, Biotechnology Journal, 8, 12, (1435-1444), (2013).
- Christine Bonnet, Céline Rigaud, Emilie Chanteclaire, Claire Blandais, Emilie Tassy-Freches, Christelle Arico and Christophe Javaud, PCR on yeast colonies: an improved method for glyco-engineered Saccharomyces cerevisiae, BMC Research Notes, 10.1186/1756-0500-6-201, 6, 1, (201), (2013).
- Yun-Soo Yeo, S. Eric Nybo, Amar G. Chittiboyina, Aruna D. Weerasooriya, Yan-Hong Wang, Elsa Góngora-Castillo, Brieanne Vaillancourt, C. Robin Buell, Dean DellaPenna, Mary Dawn Celiz, A. Daniel Jones, Eve Syrkin Wurtele, Nick Ransom, Natalia Dudareva, Khaled A. Shaaban, Nidhi Tibrewal, Suman Chandra, Troy Smillie, Ikhlas A. Khan, Robert M. Coates, David S. Watt and Joe Chappell, Functional Identification of Valerena-1,10-diene Synthase, a Terpene Synthase Catalyzing a Unique Chemical Cascade in the Biosynthesis of Biologically Active Sesquiterpenes in Valeriana officinalis , Journal of Biological Chemistry, 10.1074/jbc.M112.415836, 288, 5, (3163-3173), (2012).
- Bryan W. Pyle, Hue T. Tran, Benjamin Pickel, Tegan M. Haslam, Zhizeng Gao, Gillian MacNevin, John C. Vederas, Soo‐Un Kim and Dae‐Kyun Ro, Enzymatic synthesis of valerena‐4,7(11)‐diene by a unique sesquiterpene synthase from the valerian plant (Valeriana officinalis), The FEBS Journal, 279, 17, (3136-3146), (2012).
- S.‐Y. Hong, A.S. Zurbriggen and A. Melis, Isoprene hydrocarbons production upon heterologous transformation of Saccharomyces cerevisiae, Journal of Applied Microbiology, 113, 1, (52-65), (2012).
- Tom D. Niehaus, Scott Kinison, Shigeru Okada, Yun-soo Yeo, Stephen A. Bell, Ping Cui, Timothy P. Devarenne and Joe Chappell, Functional Identification of Triterpene Methyltransferases fromBotryococcus brauniiRace B, Journal of Biological Chemistry, 287, 11, (8163), (2012).
- Trinh-Don Nguyen, Gillian MacNevin and Dae-Kyun Ro, De Novo Synthesis of High-Value Plant Sesquiterpenoids in Yeast, Natural Product Biosynthesis by Microorganisms and Plants, Part C, 10.1016/B978-0-12-404634-4.00013-9, (261-278), (2012).
- Shuiqin Wu, Zuodong Jiang, Chase Kempinski, S. Eric Nybo, Satrio Husodo, Robert Williams and Joe Chappell, Engineering triterpene metabolism in tobacco, Planta, 236, 3, (867), (2012).
- Sotirios C. Kampranis and Antonios M. Makris, DEVELOPING A YEAST CELL FACTORY FOR THE PRODUCTION OF TERPENOIDS, Computational and Structural Biotechnology Journal, 3, 4, (e201210006), (2012).
- Thuy T. B. Ly, Yogan Khatri, Josef Zapp, Michael C. Hutter and Rita Bernhardt, CYP264B1 from Sorangium cellulosum So ce56: a fascinating norisoprenoid and sesquiterpene hydroxylase, Applied Microbiology and Biotechnology, 10.1007/s00253-011-3727-z, 95, 1, (123-133), (2012).
- Gionata Scalcinati, Christoph Knuf, Siavash Partow, Yun Chen, Jérôme Maury, Michel Schalk, Laurent Daviet, Jens Nielsen and Verena Siewers, Dynamic control of gene expression in Saccharomyces cerevisiae engineered for the production of plant sesquitepene α-santalene in a fed-batch mode, Metabolic Engineering, 10.1016/j.ymben.2012.01.007, 14, 2, (91-103), (2012).
- Marc J. C. Fischer, Sophie Meyer, Patricia Claudel, Marc Bergdoll and Francis Karst, Metabolic engineering of monoterpene synthesis in yeast, Biotechnology and Bioengineering, 108, 8, (1883-1892), (2011).
- Moran Farhi, Elena Marhevka, Tania Masci, Evgeniya Marcos, Yoram Eyal, Mariana Ovadis, Hagai Abeliovich and Alexander Vainstein, Harnessing yeast subcellular compartments for the production of plant terpenoids, Metabolic Engineering, 10.1016/j.ymben.2011.05.001, 13, 5, (474-481), (2011).
- Dae‐Kyun Ro, Terpenoid Biosynthesis, Plant Metabolism and Biotechnology, (217-240), (2011).
- , References, The Yeasts, 10.1016/B978-0-444-52149-1.00187-7, (r1-r178), (2011).
- T. D. Niehaus, S. Okada, T. P. Devarenne, D. S. Watt, V. Sviripa and J. Chappell, Identification of unique mechanisms for triterpene biosynthesis in Botryococcus braunii, Proceedings of the National Academy of Sciences, 10.1073/pnas.1106222108, 108, 30, (12260-12265), (2011).
- Chonglong Wang, Jae-Yean Kim, Eui-Sung Choi and Seon-Won Kim, Microbial production of farnesol (FOH): Current states and beyond, Process Biochemistry, 10.1016/j.procbio.2011.02.020, 46, 6, (1221-1229), (2011).
- Arul M Varman, Yi Xiao, Effendi Leonard and Yinjie J Tang, Statistics-based model for prediction of chemical biosynthesis yield from Saccharomyces cerevisiae, Microbial Cell Factories, 10.1186/1475-2859-10-45, 10, 1, (45), (2011).
- Mohammad A. Asadollahi, Jérôme Maury, Michel Schalk, Anthony Clark and Jens Nielsen, Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae, Biotechnology and Bioengineering, 106, 1, (86-96), (2010).
- Chonglong Wang, Sang‐Hwal Yoon, Asad Ali Shah, Young‐Ryun Chung, Jae‐Yean Kim, Eui‐Sung Choi, Jay D. Keasling and Seon‐Won Kim, Farnesol production from Escherichia coli by harnessing the exogenous mevalonate pathway, Biotechnology and Bioengineering, 107, 3, (421-429), (2010).
- Moran Farhi, Orly Lavie, Tania Masci, Keren Hendel-Rahmanim, David Weiss, Hagai Abeliovich and Alexander Vainstein, Identification of rose phenylacetaldehyde synthase by functional complementation in yeast, Plant Molecular Biology, 72, 3, (235), (2010).
- S. Lee, S. Badieyan, D. R. Bevan, M. Herde, C. Gatz and D. Tholl, Herbivore-induced and floral homoterpene volatiles are biosynthesized by a single P450 enzyme (CYP82G1) in Arabidopsis, Proceedings of the National Academy of Sciences, 107, 49, (21205), (2010).
- L. Daviet and M. Schalk, Biotechnology in plant essential oil production: progress and perspective in metabolic engineering of the terpene pathway, Flavour and Fragrance Journal, 25, 3, (123-127), (2010).
- Joe Chappell and Robert M. Coates, Sesquiterpenes, Comprehensive Natural Products II, 10.1016/B978-008045382-8.00005-8, (609-641), (2010).
- Braulio M. Fraga, Natural sesquiterpenoids, Natural Product Reports, 10.1039/b908720f, 26, 9, (1125), (2009).
- Makoto Hashimoto, Yusuke Higuchi, Shunji Takahashi, Hiroyuki Osada, Toshiyuki Sakaki, Tomonobu Toyomasu, Takeshi Sassa, Nobuo Kato and Tohru Dairi, Functional analyses of cytochrome P450 genes responsible for the early steps of brassicicene C biosynthesis, Bioorganic & Medicinal Chemistry Letters, 19, 19, (5640), (2009).
- Djuro Josic and Spomenka Kovač, Application of proteomics in biotechnology – Microbial proteomics, Biotechnology Journal, 3, 4, (496-509), (2008).
- J. Chappell, Production platforms for the molecular pharming of alkaloid diversity, Proceedings of the National Academy of Sciences, 105, 23, (7897), (2008).
- Shuiqin Wu and Joe Chappell, Metabolic engineering of natural products in plants; tools of the trade and challenges for the future, Current Opinion in Biotechnology, 19, 2, (145), (2008).
- Beibei Huang, Jing Guo, Bo Yi, Xiaojing Yu, Lianna Sun and Wansheng Chen, Heterologous production of secondary metabolites as pharmaceuticals in Saccharomyces cerevisiae, Biotechnology Letters, 30, 7, (1121), (2008).
- , Current awareness on yeast, Yeast, 24, 12, (1085-1092), (2007).
- Juan A. Faraldos, Shuiqin Wu, Joe Chappell and Robert M. Coates, Conformational analysis of (+)-germacrene A by variable-temperature NMR and NOE spectroscopy, Tetrahedron, 63, 32, (7733), (2007).
- Shuiqin Wu, Michel Schalk, Anthony Clark, R Brandon Miles, Robert Coates and Joe Chappell, Redirection of cytosolic or plastidic isoprenoid precursors elevates terpene production in plants, Nature Biotechnology, 24, 11, (1441), (2006).
- Ming-zhu Ding, Hui-fang Yan, Lin-feng Li, Fang Zhai, Lu-qing Shang, Zheng Yin, Ying-jin Yuan and Feng Ling, Biosynthesis of Taxadiene in Saccharomyces cerevisiae : Selection of Geranylgeranyl Diphosphate Synthase Directed by a Computer-Aided Docking Strategy, PLoS ONE, 10.1371/journal.pone.0109348, 9, 10, (e109348), (2014).
