Metabolic Characterization of Escherichia coli Strains Adapted to Growth on Lactate
Open accessAbstract
In comparison with intensive studies of genetic mechanisms related to biological evolutionary systems, much less analysis has been conducted on metabolic network responses to adaptive evolution that are directly associated with evolved metabolic phenotypes. Metabolic mechanisms involved in laboratory evolution of Escherichia coli on gluconeogenic carbon sources, such as lactate, were studied based on intracellular flux states determined from 13 C tracer experiments and 13 C-constrained flux analysis. At the end point of laboratory evolution, strains exhibited a more than doubling of the average growth rate and a 50% increase in the average biomass yield. Despite different evolutionary trajectories among parallel evolved populations, most improvements were obtained within the first 250 generations of evolution and were generally characterized by a significant increase in pathway capacity. Partitioning between gluconeogenic and pyruvate catabolic flux at the pyruvate node remained almost unchanged, while flux distributions around the key metabolites phosphoenolpyruvate, oxaloacetate, and acetyl-coenzyme A were relatively flexible over the course of evolution on lactate to meet energetic and anabolic demands during rapid growth on this gluconeogenic carbon substrate. There were no clear qualitative correlations between most transcriptional expression and metabolic flux changes, suggesting complex regulatory mechanisms at multiple levels of genetics and molecular biology. Moreover, higher fitness gains for cell growth on both evolutionary and alternative carbon sources were found for strains that adaptively evolved on gluconeogenic carbon sources compared to those that evolved on glucose. These results provide a novel systematic view of the mechanisms underlying microbial adaptation to growth on a gluconeogenic substrate.
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With suitable neutral genetic markers, fitness differences can be easily monitored during laboratory evolution of microbial cells.
“With suitable neutral genetic markers, this fitness difference can be easily monitored during laboratory evolution of microbial cells [34,59].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [59]
Certain environments can lead to fast selection of improved phenotypes, whereas others, including long-term adaptation to environmental pH, represent complex environments where microbial cells show low adaptive potential in terms of absolute fitness gain.
“Whereas certain environments can lead to fast selection of improved phenotypes, others, including the long-term adaptation to environmental pH [59,63], represent complex environments where microbial cells show low adaptive potential in terms of absolute fitness gain.”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [59]
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- Authors
- Hua, Q., Joyce, A. R., Palsson, B. Ø., & Fong, S. S.
- Affiliations
- University of California San Diego (US)
- University of San Diego (US)
- Corresponding author
- Palsson, Bernhard Ø.
- Venue
- Applied and Environmental Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2007-07-15
- Volume
- 73
- Issue
- 14
- Pages
- 4639-4647
- ISSN
- 0099-2240 (ISSN-L)
- 1098-5336
- PMC
- PMC1932837
- OpenAlex
- W2152452381
- Cited by
- 67
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Applied and Environmental Microbiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Diego
- National Institute of General Medical Sciences (R01GM057089, GM057089)
- 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, lactate metabolism, experimental evolution, metabolic adaptation, metabolic flux distribution, phosphoenolpyruvate, oxaloacetate, acetyl-CoA, growth rate, biomass yield, parallel evolution, transcriptional regulation
- MeSH terms
- Acetyl Coenzyme A, Carbon, Carbon Isotopes, Escherichia coli, Gluconeogenesis, Phosphoenolpyruvate, Transcription, Genetic, Gene Expression Regulation, Bacterial, Biomass, Pyruvic Acid, Lactic Acid, Metabolic Networks and Pathways, Oxaloacetic Acid
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