Construction and Analysis of an Enzyme-Constrained Metabolic Model of Corynebacterium glutamicum
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Abstract
The genome-scale metabolic model (GEM) is a powerful tool for interpreting and predicting cellular phenotypes under various environmental and genetic perturbations. However, GEM only considers stoichiometric constraints, and the simulated growth and product yield values will show a monotonic linear increase with increasing substrate uptake rate, which deviates from the experimentally measured values. Recently, the integration of enzymatic constraints into stoichiometry-based GEMs was proven to be effective in making novel discoveries and predicting new engineering targets. Here, we present the first genome-scale enzyme-constrained model (ecCGL1) for Corynebacterium glutamicum reconstructed by integrating enzyme kinetic data from various sources using a ECMpy workflow based on the high-quality GEM of C. glutamicum (obtained by modifying the iCW773 model). The enzyme-constrained model improved the prediction of phenotypes and simulated overflow metabolism, while also recapitulating the trade-off between biomass yield and enzyme usage efficiency. Finally, we used the ecCGL1 to identify several gene modification targets for l-lysine production, most of which agree with previously reported genes. This study shows that incorporating enzyme kinetic information into the GEM enhances the cellular phenotypes prediction of C. glutamicum, which can help identify key enzymes and thus provide reliable guidance for metabolic engineering.
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- Authors
- Niu, J., Mao, Z., Mao, Y., Wu, K., Shi, Z., Yuan, Q., Cai, J., & Ma, H.
- Affiliations
- University of Science and Technology of China (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Mao, Zhitao
- Ma, Hongwu
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2022-10-17
- Volume
- 12
- Issue
- 10
- Pages
- 1499
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC9599660
- OpenAlex
- W4306651296
- Cited by
- 32
- References
- 63
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 12 · 2023: 4 · 2022: 1
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (2018YFA0900300, NSFC-32101186, 21908239, TSBICIP-PTJS-001, 153D31KYSB20170121)
- National Natural Science Foundation of China (2018YFA0900300, NSFC-32101186, 21908239, TSBICIP-PTJS-001, 153D31KYSB20170121)
- Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (2018YFA0900300, NSFC-32101186, 21908239, TSBICIP-PTJS-001, 153D31KYSB20170121)
- International Partnership Program of Chinese Academy of Sciences (2018YFA0900300, NSFC-32101186, 21908239, TSBICIP-PTJS-001, 153D31KYSB20170121)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- Corynebacterium glutamicum, genome-scale metabolic models, enzyme kinetics, overflow metabolism, biomass yield, L-lysine production, metabolic engineering targets
- MeSH terms
- Lysine, Corynebacterium glutamicum, Metabolic Engineering
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 ›
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