Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction
Growth is a fundamental process of life. Growth requirements are well‐characterized experimentally for many microbes; however, we lack a unified model for cellular growth. Such a model must be predictive of events at the molecular scale and capable of explaining the high‐level behavior of the cell a...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
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Springer Nature
2013-01-01
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Series: | Molecular Systems Biology |
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Online Access: | https://doi.org/10.1038/msb.2013.52 |
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author | Edward J O'Brien Joshua A Lerman Roger L Chang Daniel R Hyduke Bernhard Ø Palsson |
author_facet | Edward J O'Brien Joshua A Lerman Roger L Chang Daniel R Hyduke Bernhard Ø Palsson |
author_sort | Edward J O'Brien |
collection | DOAJ |
description | Growth is a fundamental process of life. Growth requirements are well‐characterized experimentally for many microbes; however, we lack a unified model for cellular growth. Such a model must be predictive of events at the molecular scale and capable of explaining the high‐level behavior of the cell as a whole. Here, we construct an ME‐Model for Escherichia coli—a genome‐scale model that seamlessly integrates metabolic and gene product expression pathways. The model computes ∼80% of the functional proteome (by mass), which is used by the cell to support growth under a given condition. Metabolism and gene expression are interdependent processes that affect and constrain each other. We formalize these constraints and apply the principle of growth optimization to enable the accurate prediction of multi‐scale phenotypes, ranging from coarse‐grained (growth rate, nutrient uptake, by‐product secretion) to fine‐grained (metabolic fluxes, gene expression levels). Our results unify many existing principles developed to describe bacterial growth. |
first_indexed | 2024-03-07T16:44:43Z |
format | Article |
id | doaj.art-d2339f0bc6e74f0e9897c0a874ad4033 |
institution | Directory Open Access Journal |
issn | 1744-4292 |
language | English |
last_indexed | 2024-03-07T16:44:43Z |
publishDate | 2013-01-01 |
publisher | Springer Nature |
record_format | Article |
series | Molecular Systems Biology |
spelling | doaj.art-d2339f0bc6e74f0e9897c0a874ad40332024-03-03T07:10:49ZengSpringer NatureMolecular Systems Biology1744-42922013-01-0191n/an/a10.1038/msb.2013.52Genome‐scale models of metabolism and gene expression extend and refine growth phenotype predictionEdward J O'Brien0Joshua A Lerman1Roger L Chang2Daniel R Hyduke3Bernhard Ø Palsson4Department of Bioengineering, University of California San Diego La Jolla CA USADepartment of Bioengineering, University of California San Diego La Jolla CA USADepartment of Bioengineering, University of California San Diego La Jolla CA USADepartment of Bioengineering, University of California San Diego La Jolla CA USADepartment of Bioengineering, University of California San Diego La Jolla CA USAGrowth is a fundamental process of life. Growth requirements are well‐characterized experimentally for many microbes; however, we lack a unified model for cellular growth. Such a model must be predictive of events at the molecular scale and capable of explaining the high‐level behavior of the cell as a whole. Here, we construct an ME‐Model for Escherichia coli—a genome‐scale model that seamlessly integrates metabolic and gene product expression pathways. The model computes ∼80% of the functional proteome (by mass), which is used by the cell to support growth under a given condition. Metabolism and gene expression are interdependent processes that affect and constrain each other. We formalize these constraints and apply the principle of growth optimization to enable the accurate prediction of multi‐scale phenotypes, ranging from coarse‐grained (growth rate, nutrient uptake, by‐product secretion) to fine‐grained (metabolic fluxes, gene expression levels). Our results unify many existing principles developed to describe bacterial growth.https://doi.org/10.1038/msb.2013.52gene expressiongenome‐scalemetabolismmolecular efficiencyoptimality |
spellingShingle | Edward J O'Brien Joshua A Lerman Roger L Chang Daniel R Hyduke Bernhard Ø Palsson Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction Molecular Systems Biology gene expression genome‐scale metabolism molecular efficiency optimality |
title | Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction |
title_full | Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction |
title_fullStr | Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction |
title_full_unstemmed | Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction |
title_short | Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction |
title_sort | genome scale models of metabolism and gene expression extend and refine growth phenotype prediction |
topic | gene expression genome‐scale metabolism molecular efficiency optimality |
url | https://doi.org/10.1038/msb.2013.52 |
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