ArticleApplied microbiology and biotechnology2018
Upregulating the mevalonate pathway and repressing sterol synthesis in Saccharomyces cerevisiae enhances the production of triterpenes.
Article in Applied microbiology and biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 96 citations in OpenAlex.
- Multi-level metabolic engineering for squalene production: from pathway optimization to systematic regulation.World journal of microbiology & biotechnology · 2026Review
- The Mevalonate Pathway: Innovations, Applications, and Challenges in Biotechnology with Emphasis on Fungal Biology.Journal of fungi (Basel, Switzerland) · 2026Review
- High yield strategies for triterpenoid biosynthesis in cell factories.Journal of microbiology (Seoul, Korea) · 2026Review
- Production of β-carotene from methanol via rDNA-targeted multi-gene integration and selection with increasing antibiotic concentrations in Komagataella phaffii.World journal of microbiology & biotechnology · 2026Article
- Multi-omics-guided discovery of CYP5035 enables heterologous production and engineering of pachymic acid in yeast.Journal of biological engineering · 2026Article
- Hijacking competitor-derived signals: RcsB/C drivesApplied and environmental microbiology · 2026Article
- Complex Kinetic Models Predict β-Carotene Production and Reveal Flux Limitations in RecombinantACS synthetic biology · 2025Article
- Metabolic and genetic analysis links TRITERPENE SYNTHASE 12 to oleanolic acid biosynthesis in grape berry wax.Journal of experimental botany · 2025Article
- Production of borneol, camphor, and bornyl acetate using engineeredMetabolic engineering communications · 2025Article
- Metabolic Response ofMicroorganisms · 2025Article
- Rap1 overexpression boosts triterpenoid saponin production in yeast by enhancing precursor supply and heterologous gene expression.Microbial cell factories · 2025Article
- Overexpression of tRNA mFrontiers in microbiology · 2025Article
- Screening of broad-host expression promoters for shuttle expression vectors in non-conventional yeasts and bacteria.Microbial cell factories · 2024Article
- Genomic and Comparative Transcriptomic Analyses Reveal Key Genes Associated with the Biosynthesis Regulation of Okaramine B inInternational journal of molecular sciences · 2024Article
- The interaction networks of small rubber particle proteins in the latex ofFrontiers in plant science · 2024Article
- Iterative gene integration mediated by 26S rDNA and non-homologous end joining for the efficient production of lycopene in Yarrowia lipolytica.Bioresources and bioprocessing · 2023Article
- 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
- Carotenoids in Drug Discovery and Medicine: Pathways and Molecular Targets Implicated in Human Diseases.Molecules (Basel, Switzerland) · 2022Review
- Role of ROX1, SKN7, and YAP6 Stress Transcription Factors in the Production of Secondary Metabolites inInternational journal of molecular sciences · 2022Article
- CRISPRi-Guided Metabolic Flux Engineering for Enhanced Protopanaxadiol Production inInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pentacyclic triterpenes are diverse plant secondary metabolites derived from the mevalonate (MVA) pathway. Many of these molecules are potentially valuable, particularly as pharmaceuticals, and research has focused on their production in simpler and more amenable heterologous systems such as the yeast Saccharomyces cerevisiae. We have developed a new heterologous platform for the production of pentacyclic triterpenes in S. cerevisiae based on a combinatorial engineering strategy involving the overexpression of MVA pathway genes, the knockout of negative regulators, and the suppression of a competing pathway. Accordingly, we overexpressed S. cerevisiae ERG13, encoding 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase, and a truncated and deregulated variant of the rate-limiting enzyme HMG-CoA reductase 1 (tHMGR). In the same engineering step, we deleted the ROX1 gene, encoding a negative regulator of the MVA pathway and sterol biosynthesis, resulting in a push-and-pull strategy to enhance metabolic flux through the system. In a second step, we redirected this enhanced metabolic flux from late sterol biosynthesis to the production of 2,3-oxidosqualene, the direct precursor of pentacyclic triterpenes. In yeast cells transformed with a newly isolated sequence encoding lupeol synthase from the Russian dandelion (Taraxacum koksaghyz), we increased the yield of pentacyclic triterpenes by 127-fold and detected not only high levels of lupeol but also a second valuable pentacyclic triterpene product, β-amyrin.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.