Unravelling evolutionary strategies of yeast for improving galactose utilization through integrated systems level analysis
Open accessAbstract
Identification of the underlying molecular mechanisms for a derived phenotype by adaptive evolution is difficult. Here, we performed a systems-level inquiry into the metabolic changes occurring in the yeast Saccharomyces cerevisiae as a result of its adaptive evolution to increase its specific growth rate on galactose and related these changes to the acquired phenotypic properties. Three evolved mutants (62A, 62B, and 62C) with higher specific growth rates and faster specific galactose uptake were isolated. The evolved mutants were compared with a reference strain and two engineered strains, SO16 and PGM2, which also showed higher galactose uptake rate in previous studies. The profile of intermediates in galactose metabolism was similar in evolved and engineered mutants, whereas reserve carbohydrates metabolism was specifically elevated in the evolved mutants and one evolved strain showed changes in ergosterol biosynthesis. Mutations were identified in proteins involved in the global carbon sensing Ras/PKA pathway, which is known to regulate the reserve carbohydrates metabolism. We evaluated one of the identified mutations, RAS2 Tyr112 , and this mutation resulted in an increased specific growth rate on galactose. These results show that adaptive evolution results in the utilization of unpredicted routes to accommodate increased galactose flux in contrast to rationally engineered strains. Our study demonstrates that adaptive evolution represents a valuable alternative to rational design in bioengineering of improved strains and, that through systems biology, it is possible to identify mutations in evolved strain that can serve as unforeseen metabolic engineering targets for improving microbial strains for production of biofuels and chemicals.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Another study reported the emergence of aneuploidy during glucose-limited growth and amplification of the HXT6 gene with significant divergence between co-evolved S. cerevisiae populations.
“another study reported the emergence of aneuploidy during glucose-limited growth and amplification of the HXT6 gene with significant divergence between co-evolved populations [94].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [94]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network
Ideker, T., Thorsson, V., Ranish, J. A., Christmas, R., Buhler, J., Eng, J. K., Bumgarner, R., Goodlett, D. R., Aebersold, R., & Hood, L. (2001) · Science · doi:10.1126/science.292.5518.929 · Cited by 2,050 · see citing works
Genome evolution and adaptation in a long-term experiment with Escherichia coli
Barrick, J. E., Yu, D. S., Yoon, S. H., Jeong, H., Oh, T. K., Schneider, D., Lenski, R. E., & Kim, J. F. (2009) · Nature · doi:10.1038/nature08480 · Cited by 1,184 · see citing works
Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae.
François, J., & Parrou, J. (2001) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2001.tb00574.x · Cited by 631 · see citing works
Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast
Estruch, F. (2000) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2000.tb00551.x · Cited by 616 · see citing works
Herring, C. D., Raghunathan, A., Honisch, C., Patel, T., Applebee, M. K., Joyce, A. R., Albert, T. J., Blattner, F. R., van den Boom, D., Cantor, C. R., et al. (2006) · Nature Genetics · doi:10.1038/ng1906 · Cited by 381 · see citing works
NIELSEN, J. K. (2001) · Applied Microbiology and Biotechnology · doi:10.1007/s002530000511 · Cited by 315 · see citing works
Self-citationGrowth-limiting Intracellular Metabolites in Yeast Growing under Diverse Nutrient Limitations
Boer, V. M., Crutchfield, C. A., Bradley, P. H., Botstein, D., & Rabinowitz, J. D. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-07-0597 · Cited by 260 · see citing works
Wisselink, H. W., Toirkens, M. J., Wu, Q., Pronk, J. T., & van Maris, A. J. A. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.02268-08 · Cited by 247 · see citing works
Østergaard, S., Lisbeth Olsson, A., Johnston, M., & Nielsen, J. (2000) · Nature Biotechnology · doi:10.1038/82400 · Cited by 184 · see citing works
Self-citationIndustrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory
Otero, J. M., Cimini, D., Patil, K. R., Poulsen, S. G., Lisbeth Olsson, A., & Nielsen, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054144 · Cited by 167 · see citing works
Self-citationBro, C., Knudsen, S., Regenberg, B., Lisbeth Olsson, A., & Nielsen, J. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.11.6465-6472.2005 · Cited by 126 · see citing works
Self-citationEngineering Complex Phenotypes in Industrial Strains
Patnaik, R. (2007) · Biotechnology Progress · doi:10.1021/bp0701214 · Cited by 124 · see citing works
Ikeda, M., Ohnishi, J., Hayashi, M., & Mitsuhashi, S. (2006) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-006-0104-5 · Cited by 122 · see citing works
Dual feedback loops in the GAL regulon suppress cellular heterogeneity in yeast
Ramsey, S. A., Smith, J. J., Orrell, D., Marelli, M., Petersen, T. W., de Atauri, P., Bolouri, H., & Aitchison, J. D. (2006) · Nature Genetics · doi:10.1038/ng1869 · Cited by 96 · see citing works
Swan, T. M., & Watson, K. (1999) · Canadian Journal of Microbiology · doi:10.1139/w99-033 · Cited by 91 · see citing works
Otero, J. M., Vongsangnak, W., Asadollahi, M. A., Olivares‐Hernández, R., Maury, J., Farinelli, L., Bærlocher, L., Østerås, M., Schalk, M., Clark, A., et al. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-723 · Cited by 73 · see citing works
Self-citationKelly, S. L., Lamb, D. C., Corran, A. J., et al. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)01342-3 · Cited by 70 · see citing works
de Jongh, W. A., Bro, C., Østergaard, S., Regenberg, B., Lisbeth Olsson, A., & Nielsen, J. (2008) · Biotechnology and Bioengineering · doi:10.1002/bit.21890 · Cited by 67 · see citing works
Self-citationAlbers, E., & Larsson, C. (2009) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-009-0592-1 · Cited by 63 · see citing works
van den Brink, J., Akeroyd, M., van der Hoeven, R., Pronk, J. T., de Winde, J. H., & Daran-Lapujade, P. A. S. (2009) · Microbiology · doi:10.1099/mic.0.025775-0 · Cited by 56 · see citing works
Østergaard, S., Olsson, L., & NIELSEN, J. K. (2001) · Biotechnology and Bioengineering · doi:10.1002/bit.1075 · Cited by 54 · see citing works
Self-citationApplebee, M. K., Herrgård, M. J., & Palsson, B. Ø. (2008) · Journal of Bacteriology · doi:10.1128/jb.01976-07 · Cited by 51 · see citing works
Hazelwood, L., Walsh, M. C., Luttik, M., Daran-Lapujade, P., Pronk, J., & Daran, J. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.01464-09 · Cited by 38 · see citing works
Pierce, A. M., Unrau, A. M., Oehlschlager, A. C., et al. (1979) · Canadian Journal of Biochemistry · doi:10.1139/o79-025 · Cited by 35 · see citing works
Pierce, H. D., Jr., Pierce, A. M., Srinivasan, R., et al. (1978) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(78)90087-5 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adaptive laboratory evolution—Principles and applications for biotechnology
Dragosits, M., & Mattanovich, D. (2013) · Microbial Cell Factories · doi:10.1186/1475-2859-12-64 · Cited by 827 · see citing works
Nielsen, J. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044757 · Cited by 252 · see citing works
Self-citationElsemman, I. E., Rodriguez Prado, A., Grigaitis, P., Garcia Albornoz, M., Harman, V., Holman, S. W., van Heerden, J., Bruggeman, F. J., Bisschops, M. M. M., Sonnenschein, N., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28467-6 · Cited by 120 · see citing works
Self-citationEvolutionary engineering of Saccharomyces cerevisiae for efficient aerobic xylose consumption
Scalcinati, G., Otero, J. M., Vleet, J. R. H., Jeffries, T. W., Olsson, L., & Nielsen, J. (2012) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2012.00808.x · Cited by 89 · see citing works
Self-citationOud, B., Maris, A. J. A., Daran, J.-M., & Pronk, J. T. (2012) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2011.00776.x · Cited by 82 · see citing works
Kok, S., Nijkamp, J. F., Oud, B., Roque, F. C., Ridder, D., Daran, J.-M., Pronk, J. T., & Maris, A. J. A. (2012) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2011.00787.x · Cited by 65 · see citing works
- Authors
- Hong, K.-K., Vongsangnak, W., Vemuri, G. N., & Nielsen, J.
- Affiliations
- CJ CheilJedang (South Korea) (KR)
- Chalmers University of Technology (SE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-06-29
- Volume
- 108
- Issue
- 29
- Pages
- 12179-12184
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3141923
- OpenAlex
- W1987363227
- Cited by
- 161
- References
- 25
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 15 · 2018: 10 · 2017: 9 · 2016: 12 · 2015: 10 · 2014: 18 · 2013: 16 · 2012: 21
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Chalmers Publication Library (Chalmers University of Technology) (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Novo Nordisk Fonden (NNF10CC1016517)
- 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, galactose utilization, adaptive evolution, specific growth rate, galactose uptake, ergosterol biosynthesis, galactose metabolism, metabolic engineering, biofuel production
- MeSH terms
- Base Sequence, Chromatography, High Pressure Liquid, Biological Evolution, Galactose, Gas Chromatography-Mass Spectrometry, Molecular Sequence Data, Phenotype, Saccharomyces cerevisiae, Species Specificity, Mutagenesis, Site-Directed, Sequence Analysis, DNA, DNA Primers, ras Proteins, Gene Expression Profiling, Saccharomyces cerevisiae Proteins, Systems Biology, Metabolic Networks and Pathways, Bioengineering
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
