Towards Kinetic Modeling of Global Metabolic Networks: Methylobacterium extorquens AM1 Growth as Validation

doi:10.1016/S1872-2075(08)60046-1

Chinese Journal of Biotechnology

Volume 24, Issue 6, June 2008, Pages 980-994

https://doi.org/10.1016/S1872-2075(08)60046-1 Get rights and content

Abstract

Here we report a systematic method for constructing a large scale kinetic metabolic model and its initial application to the modeling of central metabolism of Methylobacterium extorquens AM1, a methylotrophic and environmental important bacterium. Its central metabolic network includes formaldehyde metabolism, serine cycle, citric acid cycle, pentose phosphate pathway, gluconeogensis, PHB synthesis and acetyl-CoA conversion pathway, respiration and energy metabolism. Through a systematic and consistent procedure of finding a set of parameters in the physiological range we overcome an outstanding difficulty in large scale kinetic modeling: the requirement for a massive number of enzymatic reaction parameters. We are able to construct the kinetic model based on general biological considerations and incomplete experimental kinetic parameters. Our method consists of the following major steps: 1) using a generic enzymatic rate equation to reduce the number of enzymatic parameters to a minimum set while still preserving their characteristics; 2) using a set of steady state fluxes and metabolite concentrations in the physiological range as the expected output steady state fluxes and metabolite concentrations for the kinetic model to restrict the parametric space of enzymatic reactions; 3) choosing enzyme constants K's and K'_eqs optimized for reactions under physiological concentrations, if their experimental values are unknown; 4) for models which do not cover the entire metabolic network of the organisms, designing a dynamical exchange for the coupling between the metabolism represented in the model and the rest not included.

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: Supported by: USA National Institutes of Health (Nos. K25-HG002894-05(P.A.) and GM36296(L.W.L. and M.E.L.)).

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RESEARCH PAPERTowards Kinetic Modeling of Global Metabolic Networks: Methylobacterium extorquens AM1 Growth as Validation

Abstract

Mech Aging Dev

Curr Opin Microbiol

Curr Opin Microbiol

Comp Chem Eng

Biophys Chem

Curr Opin Biotech

Trends Biotechnol

Introduction to Systems Biology

Predictive metabolic engineering: a goal for systems biology

Plant Physiol

Metabolomics technology and bioinformatics

Brief Bioinform

Metabolic networks in motion: 13C-based flux analysis

Mol Syst Bio

Understanding through modeling, in Konopka, Systems Biology: Principles, Methods, and Concepts

Metabolic engineering

Stochastic fluctuations in metabolic pathways

Proc Natl Acad Sci USA

Structural kinetic modeling of metabolic networks

Proc Natl Acad Sci USA

Dynamic simulations on the arachidonic acid metabolic network. PLOS

Comput Biol

Flux balance analysis in the era of metabolomics

Brief Bioinform

Stoichiometric network theory for nonequilibrium biochemical systems

Eur J Biochem

Integrating high-throughput and computational data elucidates bacterial networks

Nature

Enzyme kinetics. Behavior and analysis of rapid equilibrium and steady-state enzyme systems

A synthetic genemetabolic oscillator

Nature

From simple to complex oscillatory behavior in metabolic and genetic control networks

Chaos

Understanding bistability in complex enzyme-driven reaction networks

PNAS

Calculating robustness of epigenetic states in phage λ life cycle

Funct Integr Genomics

Methylotrophy in Methylobacterium exotorquens AM1 from a genomic point of view

J Bacteriol

The Biochemistry of Methylotrophs

Integrated Genomics Publicly Available Genomes: Methyl-obacterium extorquens AM1

RESEARCH PAPER
Towards Kinetic Modeling of Global Metabolic Networks: Methylobacterium extorquens AM1 Growth as Validation