ArticleMicrobial cell factories2015
Iterative carotenogenic screens identify combinations of yeast gene deletions that enhance sclareol production.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 74 citations in OpenAlex.
- Metabolic engineering strategies: utilizing different microbial strains and advanced technologies for the synthesis of high-valued terpenoids.Antonie van Leeuwenhoek · 2026Review
- Synthetic Biology of Sclareol: From the Plant Biosynthetic Pathway to Engineered Microbial and Photosynthetic Chassis.Biotechnology journal · 2026Review
- Diterpenoids in medicinal plants: structure, distribution, biological activities, biosynthesis, and bioengineering prospects.Frontiers in plant science · 2026Review
- A new tool for engineering Phaeodactylum tricornutum: the METE promoter drives both high expression and BThe Plant journal : for cell and molecular biology · 2025Article
- Chemical and transcriptomic analyses of leaf trichomes from Cistus creticus subsp. creticus reveal the biosynthetic pathways of certain labdane-type diterpenoids and their acetylated forms.Journal of experimental botany · 2024Article
- Development of a metabolic engineering technology to simultaneously suppress the expression of multiple genes in yeast and application in carotenoid production.World journal of microbiology & biotechnology · 2024Article
- De novo production of bioactive sesterterpenoid ophiobolins in Saccharomyces cerevisiae cell factories.Microbial cell factories · 2024Article
- Efforts toward Ambergris Biosynthesis.Chem & bio engineering · 2024Review
- Sustainable biosynthesis of valuable diterpenes in microbes.Engineering microbiology · 2023Review
- On the remarkable nonlinear optical properties of natural tomato lycopene.Scientific reports · 2022Article
- Effectiveness of recombinant Escherichia coli on the production of (R)-(+)-perillyl alcohol.BMC biotechnology · 2021Article
- Artificial Transcription Factors for Tuneable Gene Expression inFrontiers in bioengineering and biotechnology · 2021Article
- Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Integrating pathway elucidation with yeast engineering to produce polpunonic acid the precursor of the anti-obesity agent celastrol.Microbial cell factories · 2020Article
- Current Challenges and Opportunities in Non-native Chemical Production by Engineered Yeasts.Frontiers in bioengineering and biotechnology · 2020Review
- Article
- Identifying and engineering the ideal microbial terpenoid production host.Applied microbiology and biotechnology · 2019Review
- Primary and Secondary Metabolic Effects of a Key Gene Deletion (ΔApplied and environmental microbiology · 2019Article
- Comparative proteomic analyses of Hyphozyma roseonigra ATCC 20624 in response to sclareol.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2019Article
- Engineering of CYP76AH15 can improve activity and specificity towards forskolin biosynthesis in yeast.Microbial cell factories · 2018Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTerpenoids (isoprenoids) have numerous applications in flavors, fragrances, drugs and biofuels. The number of microbially produced terpenoids is increasing as new biosynthetic pathways are being elucidated. However, efforts to improve terpenoid production in yeast have mostly taken advantage of existing knowledge of the sterol biosynthetic pathway, while many additional factors may affect the output of the engineered system.
resultsAiming to develop a yeast strain that can support high titers of sclareol, a diterpene of great importance for the perfume industry, we sought to identify gene deletions that improved carotenoid, and thus potentially sclareol, production. Using a carotenogenic screen, the best 100 deletion mutants, out of 4,700 mutant strains, were selected to create a subset for further analysis. To identify combinations of deletions that cooperate to further boost production, iterative carotenogenic screens were applied, and each time the top performing gene deletions were further ranked according to the number of genetic and physical interactions known for each specific gene. The gene selected in each round was deleted and the resulting strain was employed in a new round of selection. This approach led to the development of an EG60 derived haploid strain combining six deletions (rox1, dos2, yer134c, vba5, ynr063w and ygr259c) and exhibiting a 40-fold increase in carotenoid and 12-fold increase in sclareol titers, reaching 750 mg/L sclareol in shake flask cultivation.
conclusionUsing an iterative approach, we identified novel combinations of yeast gene deletions that improve carotenoid and sclareol production titers without compromising strain growth and viability. Most of the identified deletions have not previously been implicated in sterol pathway control. Applying the same approach using a different starting point could yield alternative sets of deletions with similar or improved outcome.
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