Metabolic kinetic modeling provides insight into complex biological questions, but hurdles remain

Strutz, Jonathan; Martin, Jacob; Greene, Jennifer; Broadbelt, Linda; Tyo, Keith

doi:10.1016/j.copbio.2019.02.005

Title: Metabolic kinetic modeling provides insight into complex biological questions, but hurdles remain

Abstract

Metabolic models containing kinetic information can answer unique questions about cellular metabolism that are useful to metabolic engineering. Several kinetic modeling frameworks have recently been developed or improved. In addition, techniques for systematic identification of model structure, including regulatory interactions, have been reported. Each framework has advantages and limitations, which can make it difficult to choose the most appropriate framework. Common limitations are data availability and computational time, especially in large-scale modeling efforts. However, recently developed experimental techniques, parameter identification algorithms, as well as model reduction techniques help alleviate these computational bottlenecks. Opportunities for additional improvements may come from the rich literature in catalysis and chemical networks. In all, kinetic models are positioned to make significant impact in cellular engineering.

Authors:

Strutz, Jonathan ^[1];

^[1]; Greene, Jennifer ^[1];

^[1];

^[1]

Northwestern Univ., Evanston, IL (United States)

Publication Date:: Thu Mar 07 00:00:00 EST 2019

Research Org.:: Dow Chemical Co., Midland, MI (United States); Northwestern Univ., Evanston, IL (United States)

Sponsoring Org.:: USDOE Office of Energy Efficiency and Renewable Energy (EERE)

OSTI Identifier:: 1799347

Alternate Identifier(s):: OSTI ID: 1567956

Grant/Contract Number:: EE0007728; SC0018249; T32-GM008449-23; DEEE0007728; DESC0018249; MCB-1614953; DGE-1324585

Resource Type:: Accepted Manuscript

Journal Name:: Current Opinion in Biotechnology

Additional Journal Information:: Journal Volume: 59; Journal Issue: C; Journal ID: ISSN 0958-1669

Publisher:: Elsevier

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology

Citation Formats


                    Strutz, Jonathan, Martin, Jacob, Greene, Jennifer, Broadbelt, Linda, and Tyo, Keith. Metabolic kinetic modeling provides insight into complex biological questions, but hurdles remain.  United States: N. p., 2019. 
Web.  doi:10.1016/j.copbio.2019.02.005.

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                    Strutz, Jonathan, Martin, Jacob, Greene, Jennifer, Broadbelt, Linda, & Tyo, Keith. Metabolic kinetic modeling provides insight into complex biological questions, but hurdles remain.  United States.  https://doi.org/10.1016/j.copbio.2019.02.005

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                    Strutz, Jonathan, Martin, Jacob, Greene, Jennifer, Broadbelt, Linda, and Tyo, Keith. Thu .  
"Metabolic kinetic modeling provides insight into complex biological questions, but hurdles remain".  United States.  https://doi.org/10.1016/j.copbio.2019.02.005.  https://www.osti.gov/servlets/purl/1799347.

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@article{osti_1799347,

  title        = {Metabolic kinetic modeling provides insight into complex biological questions, but hurdles remain},

  author       = {Strutz, Jonathan and Martin, Jacob and Greene, Jennifer and Broadbelt, Linda and Tyo, Keith},

  abstractNote = {Metabolic models containing kinetic information can answer unique questions about cellular metabolism that are useful to metabolic engineering. Several kinetic modeling frameworks have recently been developed or improved. In addition, techniques for systematic identification of model structure, including regulatory interactions, have been reported. Each framework has advantages and limitations, which can make it difficult to choose the most appropriate framework. Common limitations are data availability and computational time, especially in large-scale modeling efforts. However, recently developed experimental techniques, parameter identification algorithms, as well as model reduction techniques help alleviate these computational bottlenecks. Opportunities for additional improvements may come from the rich literature in catalysis and chemical networks. In all, kinetic models are positioned to make significant impact in cellular engineering.},

  doi          = {10.1016/j.copbio.2019.02.005},

  journal      = {Current Opinion in Biotechnology},

  number       = C,

  volume       = 59,

  place        = {United States},

  year         = {Thu Mar 07 00:00:00 EST 2019},

  month        = {Thu Mar 07 00:00:00 EST 2019}

}

Copy to clipboard

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https://doi.org/10.1016/j.copbio.2019.02.005

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Title: Metabolic kinetic modeling provides insight into complex biological questions, but hurdles remain

Abstract

Citation Formats

Few regulatory metabolites coordinate expression of central metabolic genes in Escherichia coli journal, January 2017

redGEM: Systematic reduction and analysis of genome-scale metabolic reconstructions for development of consistent core metabolic models journal, July 2017

A review of computational tools for design and reconstruction of metabolic pathways journal, December 2017

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iSCHRUNK – In Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks journal, January 2016

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Current state and applications of microbial genome-scale metabolic models journal, April 2017

An algorithm for the reduction of genome-scale metabolic network models to meaningful core models journal, August 2015

Kinetically accessible yield (KAY) for redirection of metabolism to produce exo-metabolites journal, May 2017

Pathway design using de novo steps through uncharted biochemical spaces journal, January 2018

A genome-scale Escherichia coli kinetic metabolic model k-ecoli457 satisfying flux data for multiple mutant strains journal, December 2016

A cooperative strategy for parameter estimation in large scale systems biology models journal, January 2012

Ensemble Modeling of Metabolic Networks journal, December 2008

A model reduction method for biochemical reaction networks journal, January 2014

Universally Sloppy Parameter Sensitivities in Systems Biology Models journal, January 2007

Mathematical optimization applications in metabolic networks journal, November 2012

A machine learning approach to predict metabolic pathway dynamics from time-series multiomics data journal, May 2018

A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism journal, July 2016

An entropy-like index of bifurcational robustness for metabolic systems journal, April 2015

Application of machine learning to pyrolysis reaction networks: Reducing model solution time to enable process optimization journal, September 2017

A mixed-integer linear programming approach to the reduction of genome-scale metabolic networks journal, January 2017

Formulation, construction and analysis of kinetic models of metabolism: A review of modelling frameworks journal, December 2017

Exploring the diversity of complex metabolic networks journal, December 2004

MCMC_CLIB-an advanced MCMC sampling package for ODE models journal, July 2014

Frontiers of high-throughput metabolomics journal, February 2017

Systematic identification of allosteric protein-metabolite interactions that control enzyme activity in vivo journal, March 2013

Parameter identification of in vivo kinetic models: Limitations and challenges journal, July 2013

Reducing the allowable kinetic space by constructing ensemble of dynamic models with the same steady-state flux journal, January 2011

Complexity reduction of biochemical rate expressions journal, February 2008

Reverse engineering and identification in systems biology: strategies, perspectives and challenges journal, February 2014

Genome-Scale Thermodynamic Analysis of Escherichia coli Metabolism journal, February 2006

Construction of feasible and accurate kinetic models of metabolism: A Bayesian approach journal, July 2016

Maximizing the Information Content of Experiments in Systems Biology journal, January 2013

Ensemble Modeling for Robustness Analysis in engineering non-native metabolic pathways journal, September 2014

Mass Action Stoichiometric Simulation Models: Incorporating Kinetics and Regulation into Stoichiometric Models journal, January 2010

Methods and applications of absolute protein quantification in microbial systems journal, March 2016

Methods of Model Reduction for Large-Scale Biological Systems: A Survey of Current Methods and Trends journal, June 2017

Evaluation of rate law approximations in bottom-up kinetic models of metabolism journal, June 2016

A new framework for the estimation of control parameters in metabolic pathways using lin-log kinetics: Control parameter estimation using lin-log kinetics journal, July 2004

Parameter estimation in large-scale systems biology models: a parallel and self-adaptive cooperative strategy journal, January 2017

On-the-fly pruning for rate-based reaction mechanism generation journal, May 2017

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Genomewide landscape of gene–metabolome associations in Escherichia coli journal, January 2017

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A method for analysis and design of metabolism using metabolomics data and kinetic models: Application on lipidomics using a novel kinetic model of sphingolipid metabolism journal, September 2016

Personalized Whole-Cell Kinetic Models of Metabolism for Discovery in Genomics and Pharmacodynamics journal, October 2015

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A combined model reduction algorithm for controlled biochemical systems journal, February 2017

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Optimization-driven identification of genetic perturbations accelerates the convergence of model parameters in ensemble modeling of metabolic networks journal, June 2013

Few regulatory metabolites coordinate expression of central metabolic genes in Escherichia coli
journal, January 2017

redGEM: Systematic reduction and analysis of genome-scale metabolic reconstructions for development of consistent core metabolic models
journal, July 2017

A review of computational tools for design and reconstruction of metabolic pathways
journal, December 2017

Systems-level analysis of mechanisms regulating yeast metabolic flux
journal, October 2016

MINEs: open access databases of computationally predicted enzyme promiscuity products for untargeted metabolomics
journal, August 2015

Acceleration Strategies to Enhance Metabolic Ensemble Modeling Performance
journal, September 2017

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journal, October 2007

Systematic Evaluation of Methods for Integration of Transcriptomic Data into Constraint-Based Models of Metabolism
journal, April 2014

The discrepancy between data for and expectations on metabolic models: How to match experiments and computational efforts to arrive at quantitative predictions?
journal, April 2018

iSCHRUNK – In Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks
journal, January 2016

Production of biofuels and biochemicals: in need of an ORACLE
journal, August 2010

Current state and applications of microbial genome-scale metabolic models
journal, April 2017

An algorithm for the reduction of genome-scale metabolic network models to meaningful core models
journal, August 2015

Kinetically accessible yield (KAY) for redirection of metabolism to produce exo-metabolites
journal, May 2017

Pathway design using de novo steps through uncharted biochemical spaces
journal, January 2018

A genome-scale Escherichia coli kinetic metabolic model k-ecoli457 satisfying flux data for multiple mutant strains
journal, December 2016

A cooperative strategy for parameter estimation in large scale systems biology models
journal, January 2012

Ensemble Modeling of Metabolic Networks
journal, December 2008

A model reduction method for biochemical reaction networks
journal, January 2014

Universally Sloppy Parameter Sensitivities in Systems Biology Models
journal, January 2007

Mathematical optimization applications in metabolic networks
journal, November 2012

A machine learning approach to predict metabolic pathway dynamics from time-series multiomics data
journal, May 2018

A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism
journal, July 2016

An entropy-like index of bifurcational robustness for metabolic systems
journal, April 2015

Application of machine learning to pyrolysis reaction networks: Reducing model solution time to enable process optimization
journal, September 2017

A mixed-integer linear programming approach to the reduction of genome-scale metabolic networks
journal, January 2017

Formulation, construction and analysis of kinetic models of metabolism: A review of modelling frameworks
journal, December 2017

Exploring the diversity of complex metabolic networks
journal, December 2004

MCMC_CLIB-an advanced MCMC sampling package for ODE models
journal, July 2014

Frontiers of high-throughput metabolomics
journal, February 2017

Systematic identification of allosteric protein-metabolite interactions that control enzyme activity in vivo
journal, March 2013

Parameter identification of in vivo kinetic models: Limitations and challenges
journal, July 2013

Reducing the allowable kinetic space by constructing ensemble of dynamic models with the same steady-state flux
journal, January 2011

Complexity reduction of biochemical rate expressions
journal, February 2008

Reverse engineering and identification in systems biology: strategies, perspectives and challenges
journal, February 2014

Genome-Scale Thermodynamic Analysis of Escherichia coli Metabolism
journal, February 2006

Construction of feasible and accurate kinetic models of metabolism: A Bayesian approach
journal, July 2016

Maximizing the Information Content of Experiments in Systems Biology
journal, January 2013

Ensemble Modeling for Robustness Analysis in engineering non-native metabolic pathways
journal, September 2014

Mass Action Stoichiometric Simulation Models: Incorporating Kinetics and Regulation into Stoichiometric Models
journal, January 2010

Methods and applications of absolute protein quantification in microbial systems
journal, March 2016

Methods of Model Reduction for Large-Scale Biological Systems: A Survey of Current Methods and Trends
journal, June 2017

Evaluation of rate law approximations in bottom-up kinetic models of metabolism
journal, June 2016

A new framework for the estimation of control parameters in metabolic pathways using lin-log kinetics: Control parameter estimation using lin-log kinetics
journal, July 2004

Parameter estimation in large-scale systems biology models: a parallel and self-adaptive cooperative strategy
journal, January 2017

On-the-fly pruning for rate-based reaction mechanism generation
journal, May 2017

Stability of Ensemble Models Predicts Productivity of Enzymatic Systems
journal, March 2016

Genomewide landscape of gene–metabolome associations in Escherichia coli
journal, January 2017

A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication
journal, January 2018

A method for analysis and design of metabolism using metabolomics data and kinetic models: Application on lipidomics using a novel kinetic model of sphingolipid metabolism
journal, September 2016

Personalized Whole-Cell Kinetic Models of Metabolism for Discovery in Genomics and Pharmacodynamics
journal, October 2015

Model reduction and a priori kinetic parameter identifiability analysis using metabolome time series for metabolic reaction networks with linlog kinetics
journal, January 2009

A combined model reduction algorithm for controlled biochemical systems
journal, February 2017

RetroPath2.0: A retrosynthesis workflow for metabolic engineers
journal, January 2018

Optimization-driven identification of genetic perturbations accelerates the convergence of model parameters in ensemble modeling of metabolic networks
journal, June 2013