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Elimination of enzymes catalysis compartmentalization enhancing taxadiene production in Saccharomyces cerevisiae
Open accessAbstract
Taxadiene is an important precursor in taxol biosynthesis pathway, but its biosynthesis in eukaryotic cell factories is limited, which seriously hinders the biosynthesis of taxol. In this study, it is found that there was the catalysis compartmentalization between two key exogenous enzymes of geranylgeranyl pyrophosphate synthase and taxadiene synthase (TS) for taxadiene synthesis progress, due to their different subcellular localization. Firstly, the enzyme-catalysis compartmentalization was overcome by means of the intracellular relocation strategies of taxadiene synthase, including N-terminal truncation of taxadiene synthase and enzyme fusion of GGPPS-TS. With the help of two strategies for enzyme relocation, the taxadiene yield was increased by 21% and 54% respectively, among them the GGPPS-TS fusion enzyme is more effective. Further, the expression of GGPPS-TS fusion enzyme was improved via the multi-copy plasmid, resulting that the taxadiene titer was increased by 38% to 21.8 mg/L at shake-flask level. Finally, the maximum taxadiene titer of 184.2 mg/L was achieved by optimization of the fed-batch fermentation conditions in 3 L bioreactor, which is the highest reported titer of taxadiene biosynthesis accomplished in eukaryotic microbes. This study provides a successful example for improving biosynthesis of complex natural products by solving the critical problem of multistep enzymes catalysis compartmentalization.
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Engineered Saccharomyces cerevisiae has achieved taxadiene titres of up to 184 mg/L in fed-batch bioreactor cultivation, approximately 10-fold higher on a volumetric basis than the cyanobacterial oxygenated taxane titres reported by Zhong et al.
“For comparison, engineered Saccharomyces cerevisiae has achieved taxadiene titres of up to 184 mg/L in fed-batch bioreactor cultivation [181], approximately 10-fold higher on a volumetric basis than the cyanobacterial oxygenated taxane titres reported by Zhong et al.”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [181]
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Metadata
- Authors
- Zhang, C., Chen, W., Dong, T., Wang, Y., Yao, M., Xiao, W., & Li, B.
- Affiliations
- Tianjin University (CN)
- Georgia Institute of Technology (US)
- Corresponding author
- Yao, Mingdong
- Venue
- Frontiers in Bioengineering and Biotechnology
- Publisher
- Frontiers Media SA
- Published
- 2023-02-20
- Volume
- 11
- Pages
- 1141272-1141272
- ISSN
- 2296-4185 (ISSN-L)
- PMC
- PMC9986319
- OpenAlex
- W4321376802
- Cited by
- 16
- References
- 51
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Bioengineering and Biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (, 21621004, 2018YFA0900702, 21676192)
- National Key Research and Development Program of China (21621004, 2018YFA0900702)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant tissue culture and regeneration
- Keywords
- taxol biosynthesis, Saccharomyces cerevisiae, enzyme compartmentalization, taxadiene synthase, geranylgeranyl pyrophosphate synthase, enzyme fusion, subcellular localization, N-terminal truncation, fed-batch fermentation, natural product biosynthesis
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