The DOI matches its Crossref record; 22 of the 23 references it cites were found in a registry or an index.
Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth
Abstract
Annotated genome sequences can be used to reconstruct whole-cell metabolic networks. These metabolic networks can be modelled and analysed (computed) to study complex biological functions. In particular, constraints-based in silico models have been used to calculate optimal growth rates on common carbon substrates, and the results were found to be consistent with experimental data under many but not all conditions. Optimal biological functions are acquired through an evolutionary process. Thus, incorrect predictions of in silico models based on optimal performance criteria may be due to incomplete adaptive evolution under the conditions examined. Escherichia coli K-12 MG1655 grows sub-optimally on glycerol as the sole carbon source. Here we show that when placed under growth selection pressure, the growth rate of E. coli on glycerol reproducibly evolved over 40 days, or about 700 generations, from a sub-optimal value to the optimal growth rate predicted from a whole-cell in silico model. These results open the possibility of using adaptive evolution of entire metabolic networks to realize metabolic states that have been determined a priori based on in silico analysis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Whereas small-scale cultivations and initial engineering steps are often performed in complex media in batch culture, during the scale-up of the process, cells are exposed to altered environmental conditions and environmental stress regimes [57,58].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [57]
Citations
Cites
The complete genome sequence of Escherichia coli K-12.
Blattner, F., Plunkett, G., Bloch, C., Perna, N., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C., Mayhew, G., et al. (1997) · Science · doi:10.1126/science.277.5331.1453 · Cited by 7,996
Understanding the control of metabolism
(1997) · Choice Reviews Online · doi:10.5860/choice.34-6252 · Cited by 1,230
Varma, A., & Palsson, B. Ø. (1994) · Applied and Environmental Microbiology · doi:10.1128/aem.60.10.3724-3731.1994 · Cited by 1,058
Self-citationSchuster, S., Fell, D. A., & Dandekar, T. (2000) · Nature Biotechnology · doi:10.1038/73786 · Cited by 947
Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use
Varma, A., & Palsson, B. Ø. (1994) · Nature Biotechnology · doi:10.1038/nbt1094-994 · Cited by 945
Self-citationEdwards, J. S., Ibarra, R. U., & Palsson, B. Ø. (2001) · Nature Biotechnology · doi:10.1038/84379 · Cited by 941
Self-citationEdwards, J. S., & Palsson, B. O. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5528 · Cited by 875
Self-citationE-CELL: software environment for whole-cell simulation
Tomita, M., Hashimoto, K., Takahashi, K., Shimizu, T. S., Matsuzaki, Y., Miyoshi, F., Saito, K., Tanida, S., Yugi, K., Venter, J. C., et al. (1999) · Bioinformatics · doi:10.1093/bioinformatics/15.1.72 · Cited by 764
Karp, P. D. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.56 · Cited by 453
WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction
Overbeek, R. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.123 · Cited by 386
Flux analysis of underdetermined metabolic networks: the quest for the missing constraints
Bonarius, H. P. J., Schmid, G., & TRAMPER, J. (1997) · Trends in biotechnology · doi:10.1016/s0167-7799(97)01067-6 · Cited by 332
Genome-Scale Metabolic Model of Helicobacter pylori 26695
Schilling, C. H., Covert, M. W., Famili, I., Church, G. M., Edwards, J. S., & Palsson, B. Ø. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.16.4582-4593.2002 · Cited by 326
Self-citationMetabolic modeling of microbial strains in silico
Covert, M. W., Schilling, C. H., Famili, I., Edwards, J. S., Goryanin, I., Selkov, E., & Palsson, B. Ø. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01754-0 · Cited by 312
Self-citationThe challenges of in silico biology
Palsson, B. Ø. (2000) · Nature Biotechnology · doi:10.1038/81125 · Cited by 306
Self-citationSchilling, C. H., Edwards, J. S., Letscher, D., & Palsson, B. Ø. (2000) · Biotechnology and Bioengineering · doi:10.1002/1097-0290(2000)71:4 · Cited by 216
Self-citationModeling and simulation: tools for metabolic engineering
Wiechert, W. (2002) · Journal of Biotechnology · doi:10.1016/s0168-1656(01)00418-7 · Cited by 206
Metabolic engineering of bacteria for ethanol production
Ingram, L. O., Gomez, P. F., Lai, X., Moniruzzaman, M., Wood, B. E., Yomano, L. P., & York, S. W. (1998) · Biotechnology and Bioengineering · doi:10.1002/(sici)1097-0290(19980420)58:2/3 · Cited by 197
Mathematical modelling of metabolism
Gombert, A. K., & Nielsen, J. (2000) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(00)00079-3 · Cited by 187
Characterizing the metabolic phenotype: A phenotype phase plane analysis
Edwards, J. S., Ramakrishna, R., & Palsson, B. Ø. (2001) · Biotechnology and Bioengineering · doi:10.1002/bit.10047 · Cited by 173
Self-citationA reconstruction of the metabolism of Methanococcus jannaschii from sequence data
Selkov, E., Maltsev, N., Olsen, G. J., Overbeek, R., & Whitman, W. B. (1997) · Gene · doi:10.1016/s0378-1119(97)00307-7 · Cited by 117
Weikert, C., Sauer, U., & Bailey, J. E. (1997) · Microbiology · doi:10.1099/00221287-143-5-1567 · Cited by 63
The Department of Energy Microbial Cell Project: A 180° Paradigm Shift for Biology
Drell, D. W. (2002) · OMICS A Journal of Integrative Biology · doi:10.1089/15362310252780799 · Cited by 12
Flagged first, then by citations
1 of the 23 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Edwards, J. S., Ramakrishna, R., Schilling, C. H. & Palsson, B. O. Metabolic Engineering (eds Lee, S. Y. and Papoutsakis, E. T.) (Marcel Dekker, New York, 1999)
Cited by
Sorted by citations
Network biology: understanding the cell's functional organization
Barabási, A.-L., & Oltvai, Z. N. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1272 · Cited by 7,903
“, which allow the flux for each reaction to be calculated, have recently significantly improved our ability to make quantifiable predictions on the relative importance of various reactions, giving rise to experimentally testable hypothese”
BackgroundAbsolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli
Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., & Rabinowitz, J. D. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.186 · Cited by 1,830
“These include glutamate and αketoglutarate (23) competing for the active site of aspartate aminotransferase (with Km of 0.”
BackgroundGlobal reconstruction of the human metabolic network based on genomic and bibliomic data
Duarte, N. C., Becker, S. A., Jamshidi, N., Thiele, I., Mo, M. L., Vo, T. D., Srivas, R., & Palsson, B. Ø. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610772104 · Cited by 1,374
Self-citationEvolution Experiments with Microorganisms: The Dynamics and Genetic Bases of Adaptation
Elena, S. F., & Lenski, R. E. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1088 · Cited by 1,386
Engineering Cellular Metabolism
Nielsen, J., & Keasling, J. D. (2016) · Cell · doi:10.1016/j.cell.2016.02.004 · Cited by 1,400
Metadata
- Authors
- Ibarra, R. U., Edwards, J. S., & Palsson, B. O.
- Affiliations
- University of California San Diego (US)
- University of Delaware (US)
- ORCID
- Edwards, Jeremy S.
- Venue
- Nature
- Published
- 2002-11
- Volume
- 420
- Issue
- 6912
- Pages
- 186-189
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2025663053
- Cited by
- 857
- References
- 23
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 22 · 2023: 21 · 2022: 17 · 2021: 27 · 2020: 23 · 2019: 29 · 2018: 34 · 2017: 42 · 2016: 44 · 2015: 34 · 2014: 46 · 2013: 41 · 2012: 51
- FWCI
- 12.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- U.S. Department of Energy
- Istituto Superiore di Sanità
- National Institutes of Health
- Biological and Environmental Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- Escherichia coli K-12, adaptive evolution, optimal growth rate, glycerol metabolism, constraint-based metabolic modeling, in silico prediction, metabolic network evolution, carbon source utilization
- MeSH terms
- Adaptation, Physiological, Carbon, Computer Simulation, Escherichia coli, Biological Evolution, Glucose, Glycerol, Kinetics, Malates, Models, Biological, Phenotype, Selection, Genetic, Genome, Bacterial, Computational Biology, Acetic Acid, Succinic Acid, Genomics
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
