ArticlePloS one2014
Biosynthesis of Taxadiene in Saccharomyces cerevisiae : selection of geranylgeranyl diphosphate synthase directed by a computer-aided docking strategy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 89 citations in OpenAlex.
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- Multiplex metabolic engineering of yeast for high-efficiency all-trans-retinoic acid production.Microbial cell factories · 2025Article
- Engineering Saccharomyces cerevisiae for medical applications.Microbial cell factories · 2025Review
- Different transcriptomic and metabolomic analysis of Saccharomyces cerevisiae BY4742 and CEN.PK2-1C strains.Archives of microbiology · 2024Article
- Metabolic engineering of Saccharomyces cerevisiae for enhanced taxadiene production.Microbial cell factories · 2024Article
- Enhancing the biosynthesis of taxadien-5α-yl-acetate in Escherichia coli by combinatorial metabolic engineering approaches.Bioresources and bioprocessing · 2024Article
- Research Advances in Clinical Applications, Anticancer Mechanism, Total Chemical Synthesis, Semi-Synthesis and Biosynthesis of Paclitaxel.Molecules (Basel, Switzerland) · 2023Review
- Identification and Functional Analysis of Two Novel Genes-Geranylgeranyl Pyrophosphate Synthase Gene (Marine drugs · 2023Article
- Genetic approaches in improving biotechnological production of taxanes: An update.Frontiers in plant science · 2023Review
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- EnhancingMicroorganisms · 2022Article
- Synthetic Biology in Plants, a Boon for Coming Decades.Molecular biotechnology · 2021Review
- Biosynthesis and regulation of terpenoids from basidiomycetes: exploration of new research.AMB Express · 2021Review
- Evolution-aided engineering of plant specialized metabolism.aBIOTECH · 2021Review
- Heterologous production of cyanobacterial compounds.Journal of industrial microbiology & biotechnology · 2021Review
- Recent Advances in Metabolic Engineering, Protein Engineering, and Transcriptome-Guided Insights Toward Synthetic Production of Taxol.Frontiers in bioengineering and biotechnology · 2021Review
- Artificial Transcription Factors for Tuneable Gene Expression inFrontiers in bioengineering and biotechnology · 2021Article
- A Compressive Review about TaxolMolecules (Basel, Switzerland) · 2020Review
- Application of combinatorial optimization strategies in synthetic biology.Nature communications · 2020Review
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Authors and funding
7 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Identification of efficient key enzymes in biosynthesis pathway and optimization of the fitness between functional modules and chassis are important for improving the production of target compounds. In this study, the taxadiene biosynthesis pathway was firstly constructed in yeast by transforming ts gene and overexpressing erg20 and thmgr. Then, the catalytic capabilities of six different geranylgeranyl diphosphate synthases (GGPPS), the key enzyme in mevalonic acid (MVA) pathway catalyzing famesyl diphosphate (FPP) to geranylgeranyl diphosphate (GGPP), were predicted using enzyme-substrate docking strategy. GGPPSs from Taxus baccata x Taxus cuspidate (GGPPSbc), Erwinia herbicola (GGPPSeh), and S. cerevisiae (GGPPSsc) which ranked 1st, 4th and 6th in docking with FPP were selected for construction. The experimental results were consistent with the computer prediction that the engineered yeast with GGPPSbc exhibited the highest production. In addition, two chassis YSG50 and W303-1A were chosen, and the titer of taxadiene reached 72.8 mg/L in chassis YSG50 with GGPPSbc. Metabolomic study revealed that the contents of tricarboxylic acid cycle (TCA) intermediates and their precursor amino acids in chassis YSG50 was lower than those in W303-1A, indicating less carbon flux was divided into TCA cycle. Furthermore, the levels of TCA intermediates in the taxadiene producing yeasts were lower than those in chassis YSG50. Thus, it may result in more carbon flux in MVA pathway in chassis YSG50, which suggested that YSG50 was more suitable for engineering the taxadiene producing yeast. These results indicated that computer-aided protein modeling directed isoenzyme selection strategy and metabolomic study could guide the rational design of terpenes biosynthetic cells.
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