ArticleMicrobial cell factories2021
Improved production of germacrene A, a direct precursor of ß-elemene, in engineered Saccharomyces cerevisiae by expressing a cyanobacterial germacrene A synthase.
Article in Microbial cell factories, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 52 citations in OpenAlex.
- EngineeringSynthetic and systems biotechnology · 2025Article
- Advances in semi-rational design of terpene synthases and their modifying enzymes.AMB Express · 2025Review
- Exploration and mutagenesis of the germacrene A synthase fromSynthetic and systems biotechnology · 2025Article
- Characterization and functional reconstruction of a highly productive germacrene A synthase from Liriodendron chinense.Plant biotechnology journal · 2025Article
- Biosynthesis of Edible Terpenoids: Hosts and Applications.Foods (Basel, Switzerland) · 2025Review
- Engineering terpene synthases and their substrates for the biocatalytic production of terpene natural products and analogues.Chemical communications (Cambridge, England) · 2025Review
- Efficient biosynthesis ofSynthetic and systems biotechnology · 2025Article
- High-level biosynthesis of enantiopure germacrene D in yeast.Applied microbiology and biotechnology · 2024Article
- Recent advances in lycopene and germacrene a biosynthesis and their role as antineoplastic drugs.World journal of microbiology & biotechnology · 2024Review
- Biosynthesis Progress of High-Energy-Density Liquid Fuels Derived from Terpenes.Microorganisms · 2024Review
- An Investigation of the JAZ Family and the CwMYC2-like Protein to Reveal Their Regulation Roles in the MeJA-Induced Biosynthesis of β-Elemene inInternational journal of molecular sciences · 2023Article
- Switching carbon metabolic flux for enhancing the production of sesquiterpene-based high-density biofuel precursor in Saccharomyces cerevisiae.Biotechnology for biofuels and bioproducts · 2023Article
- Development of a Pichia pastoris cell factory for efficient production of germacrene A: a precursor of β-elemene.Bioresources and bioprocessing · 2023Article
- Protein Engineering of a Germacrene A Synthase FromFrontiers in plant science · 2022Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe sesquiterpene germacrene A is a direct precursor of ß-elemene that is a major component of the Chinese medicinal herb Curcuma wenyujin with prominent antitumor activity. The microbial platform for germacrene A production was previously established in Saccharomyces cerevisiae using the germacrene A synthase (LTC2) of Lactuca sativa.
resultsWe evaluated the performance of LTC2 (LsGAS) as well as nine other identified or putative germacrene A synthases from different sources for the production of germacrene A. AvGAS, a synthase of Anabaena variabilis, was found to be the most efficient in germacrene A production in yeast. AvGAS expression alone in S. cerevisiae CEN.PK2-1D already resulted in a substantial production of germacrene A while LTC2 expression did not. Further metabolic engineering the yeast using known strategies including overexpression of tHMGR1 and repression of squalene synthesis pathway led to an 11-fold increase in germacrene A production. Site-directed mutagenesis of AvGAS revealed that while changes of several residues located within the active site cavity severely compromised germacrene A production, substitution of Phe23 located on the lateral surface with tryptophan or valine led to a 35.2% and 21.8% increase in germacrene A production, respectively. Finally, the highest production titer of germacrene A reached 309.8 mg/L in shake-flask batch culture.
conclusionsOur study highlights the potential of applying bacterial sesquiterpene synthases with improved performance by mutagenesis engineering in producing germacrene A.
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