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Engineering Yeast Transcription Machinery for Improved Ethanol Tolerance and Production
Abstract
Global transcription machinery engineering (gTME) is an approach for reprogramming gene transcription to elicit cellular phenotypes important for technological applications. Here we show the application of gTME to Saccharomyces cerevisiae for improved glucose/ethanol tolerance, a key trait for many biofuels programs. Mutagenesis of the transcription factor Spt15p and selection led to dominant mutations that conferred increased tolerance and more efficient glucose conversion to ethanol. The desired phenotype results from the combined effect of three separate mutations in the SPT15 gene [serine substituted for phenylalanine (Phe 177 Ser) and, similarly, Tyr 195 His, and Lys 218 Arg]. Thus, gTME can provide a route to complex phenotypes that are not readily accessible by traditional methods.
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“For example, laboratory selection can lead to large-scale rewiring of gene regulatory networks, but an approach, that the authors called gTME, global transcription machinery engineering, can also yield similar results [2].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [2]
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Research works printed but not linked: 2
- H. Alper thesis Massachusetts Institute of Technology (2006).
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MethodCRISPR Gene Perturbations Provide Insights for Improving Bacterial Biofuel Tolerance
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InfluentialCOMBINATORIAL APPROACHES FOR INVERSE METABOLIC ENGINEERING APPLICATIONS
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“…polygenic basis of alcohol tolerance for improving ethanologenic yeasts, several studies have been conducted using various approaches, such as transcriptomics [3, 59], screening of genome-wide knockout collections [59], global transcriptional machinery engineering [60], and QTL mapping [8, 10, 14].”
MethodConstruction of Escherichia Coli Cell Factories for Production of Organic Acids and Alcohols
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“From the point of view of applied microbiology and biotechnology, whose ultimate goal is strain improvement, we believe that these and other method (Widianto et al. 1997) to generate genetic diversity along with recently developed whole cell engineering approaches, e.g., global transcriptional machinery engineering (…”
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“Classically, dominant mutations have been widely used to probe gene function, [21] improve tolerances and drug resistances, [22,23,24] characterize disease states, [25,26,27,28] and map protein functional domains [29].”
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“RpoD ( σ 70 ) (Alper et al. 2006 ) and cyclic AMP receptor protein (CRP) are the most studied and reported global transcription factors.”
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Method
Metadata
- Authors
- Alper, H., Moxley, J., Nevoigt, E., Fink, G. R., & Stephanopoulos, G.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Stephanopoulos, Gregory
- Venue
- Science
- Published
- 2006-12-08
- Volume
- 314
- Issue
- 5805
- Pages
- 1565-1568
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2080537888
- Cited by
- 823
- References
- 26
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 31 · 2023: 18 · 2022: 28 · 2021: 39 · 2020: 43 · 2019: 37 · 2018: 39 · 2017: 44 · 2016: 49 · 2015: 61 · 2014: 55 · 2013: 57 · 2012: 68
- FWCI
- 14.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM035010)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Physical Sciences › Engineering › Biomedical Engineering › Biofuel production and bioconversion
- Keywords
- Saccharomyces cerevisiae, ethanol tolerance, glucose fermentation, transcription factor mutations, dominant mutations, biofuel production, yeast strain engineering
- MeSH terms
- Ethanol, Fermentation, Genetic Engineering, Glucose, Phenotype, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Transformation, Genetic, Up-Regulation, Gene Expression Regulation, Fungal, Mutagenesis, Cell Cycle Proteins, Amino Acid Substitution, Gene Expression Profiling, Saccharomyces cerevisiae Proteins, TATA-Box Binding Protein, Transcription Factor TFIID, TATA-Binding Protein Associated Factors
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