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...

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Main Authors: Edward J O'Brien, Joshua A Lerman, Roger L Chang, Daniel R Hyduke, Bernhard Ø Palsson
Format: Article
Language:English
Published: Springer Nature 2013-01-01
Series:Molecular Systems Biology
Subjects:
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.
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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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AT rogerlchang genomescalemodelsofmetabolismandgeneexpressionextendandrefinegrowthphenotypeprediction
AT danielrhyduke genomescalemodelsofmetabolismandgeneexpressionextendandrefinegrowthphenotypeprediction
AT bernhardøpalsson genomescalemodelsofmetabolismandgeneexpressionextendandrefinegrowthphenotypeprediction