Clostridium butyricum maximizes growth while minimizing enzyme usage and ATP production: Metabolic flux distribution of a strain cultured in glycerol

Luis Miguel Serrano-Bermúdez, Andrés Fernando González Barrios, Costas D. Maranas, Dolly Montoya

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: The increase in glycerol obtained as a byproduct of biodiesel has encouraged the production of new industrial products, such as 1,3-propanediol (PDO), using biotechnological transformation via bacteria like Clostridium butyricum. However, despite the increasing role of Clostridium butyricum as a bio-production platform, its metabolism remains poorly modeled. Results: We reconstructed iCbu641, the first genome-scale metabolic (GSM) model of a PDO producer Clostridium strain, which included 641 genes, 365 enzymes, 891 reactions, and 701 metabolites. We found an enzyme expression prediction of nearly 84% after comparison of proteomic data with flux distribution estimation using flux balance analysis (FBA). The remaining 16% corresponded to enzymes directionally coupled to growth, according to flux coupling findings (FCF). The fermentation data validation also revealed different phenotype states that depended on culture media conditions; for example, Clostridium maximizes its biomass yield per enzyme usage under glycerol limitation. By contrast, under glycerol excess conditions, Clostridium grows sub-optimally, maximizing biomass yield while minimizing both enzyme usage and ATP production. We further evaluated perturbations in the GSM model through enzyme deletions and variations in biomass composition. The GSM predictions showed no significant increase in PDO production, suggesting a robustness to perturbations in the GSM model. We used the experimental results to predict that co-fermentation was a better alternative than iCbu641 perturbations for improving PDO yields. Conclusions: The agreement between the predicted and experimental values allows the use of the GSM model constructed for the PDO-producing Clostridium strain to propose new scenarios for PDO production, such as dynamic simulations, thereby reducing the time and costs associated with experimentation.

Original languageEnglish (US)
Article number58
JournalBMC systems biology
Volume11
Issue number1
DOIs
StatePublished - Jun 1 2017

Fingerprint

Clostridium butyricum
Clostridium
Propylene Glycols
Adenosinetriphosphate
Glycerol
Enzymes
Genes
Adenosine Triphosphate
Maximise
Fluxes
Genome
Biomass
Growth
Fermentation
Perturbation
Production platforms
Biofuels
Prediction
Proteomics
Metabolites

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Modeling and Simulation
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

Cite this

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title = "Clostridium butyricum maximizes growth while minimizing enzyme usage and ATP production: Metabolic flux distribution of a strain cultured in glycerol",
abstract = "Background: The increase in glycerol obtained as a byproduct of biodiesel has encouraged the production of new industrial products, such as 1,3-propanediol (PDO), using biotechnological transformation via bacteria like Clostridium butyricum. However, despite the increasing role of Clostridium butyricum as a bio-production platform, its metabolism remains poorly modeled. Results: We reconstructed iCbu641, the first genome-scale metabolic (GSM) model of a PDO producer Clostridium strain, which included 641 genes, 365 enzymes, 891 reactions, and 701 metabolites. We found an enzyme expression prediction of nearly 84{\%} after comparison of proteomic data with flux distribution estimation using flux balance analysis (FBA). The remaining 16{\%} corresponded to enzymes directionally coupled to growth, according to flux coupling findings (FCF). The fermentation data validation also revealed different phenotype states that depended on culture media conditions; for example, Clostridium maximizes its biomass yield per enzyme usage under glycerol limitation. By contrast, under glycerol excess conditions, Clostridium grows sub-optimally, maximizing biomass yield while minimizing both enzyme usage and ATP production. We further evaluated perturbations in the GSM model through enzyme deletions and variations in biomass composition. The GSM predictions showed no significant increase in PDO production, suggesting a robustness to perturbations in the GSM model. We used the experimental results to predict that co-fermentation was a better alternative than iCbu641 perturbations for improving PDO yields. Conclusions: The agreement between the predicted and experimental values allows the use of the GSM model constructed for the PDO-producing Clostridium strain to propose new scenarios for PDO production, such as dynamic simulations, thereby reducing the time and costs associated with experimentation.",
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Clostridium butyricum maximizes growth while minimizing enzyme usage and ATP production : Metabolic flux distribution of a strain cultured in glycerol. / Serrano-Bermúdez, Luis Miguel; González Barrios, Andrés Fernando; Maranas, Costas D.; Montoya, Dolly.

In: BMC systems biology, Vol. 11, No. 1, 58, 01.06.2017.

Research output: Contribution to journalArticle

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T1 - Clostridium butyricum maximizes growth while minimizing enzyme usage and ATP production

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AU - Serrano-Bermúdez, Luis Miguel

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AB - Background: The increase in glycerol obtained as a byproduct of biodiesel has encouraged the production of new industrial products, such as 1,3-propanediol (PDO), using biotechnological transformation via bacteria like Clostridium butyricum. However, despite the increasing role of Clostridium butyricum as a bio-production platform, its metabolism remains poorly modeled. Results: We reconstructed iCbu641, the first genome-scale metabolic (GSM) model of a PDO producer Clostridium strain, which included 641 genes, 365 enzymes, 891 reactions, and 701 metabolites. We found an enzyme expression prediction of nearly 84% after comparison of proteomic data with flux distribution estimation using flux balance analysis (FBA). The remaining 16% corresponded to enzymes directionally coupled to growth, according to flux coupling findings (FCF). The fermentation data validation also revealed different phenotype states that depended on culture media conditions; for example, Clostridium maximizes its biomass yield per enzyme usage under glycerol limitation. By contrast, under glycerol excess conditions, Clostridium grows sub-optimally, maximizing biomass yield while minimizing both enzyme usage and ATP production. We further evaluated perturbations in the GSM model through enzyme deletions and variations in biomass composition. The GSM predictions showed no significant increase in PDO production, suggesting a robustness to perturbations in the GSM model. We used the experimental results to predict that co-fermentation was a better alternative than iCbu641 perturbations for improving PDO yields. Conclusions: The agreement between the predicted and experimental values allows the use of the GSM model constructed for the PDO-producing Clostridium strain to propose new scenarios for PDO production, such as dynamic simulations, thereby reducing the time and costs associated with experimentation.

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