Dynamic model for isopropanol production by Cupriavidus necator

Abstract The Hybrid Cybernetic Model (HCM) enables the simulation of metabolic fluxes by using Elementary Modes Analysis and taking into account of selected cellular regulations. These latter are represented by cybernetic control variables. In this study, a simplified metabolic network was established in order to isolate a subset of Elementary Modes, representative of the main phenotypic capabilities of the microorganism. An innovative classification of the modes was introduced in the dynamic model, which permitted the selection of the active modes based on the microbial kinetics. The case study presented here is a genetically modified strain of Cupriavidus necator, engineered to produce isopropanol. Available experimental data were used for identification of parameters in the dynamic model. This model can be used in order to predict the value of maximal and minimal product yields when other substrates will be tested.

[1]  Etienne Paul,et al.  Impact of sustaining a controlled residual growth on polyhydroxybutyrate yield and production kinetics in Cupriavidus necator. , 2013, Bioresource technology.

[2]  Robert Urbanczik,et al.  The geometry of the flux cone of a metabolic network. , 2005, Biophysical journal.

[3]  Anthony J. Sinskey,et al.  Isopropanol production with engineered Cupriavidus necator as bioproduction platform , 2014, Applied Microbiology and Biotechnology.

[4]  D. Fell,et al.  Reaction routes in biochemical reaction systems: Algebraic properties, validated calculation procedure and example from nucleotide metabolism , 2002, Journal of mathematical biology.

[5]  J. Liao,et al.  Improvement of isopropanol production by metabolically engineered Escherichia coli using gas stripping. , 2010, Journal of bioscience and bioengineering.

[6]  D. Ramkrishna,et al.  Modeling metabolic systems: the need for dynamics , 2013 .

[7]  U. Eberhardt,et al.  Regulatory Phenomena in the Metabolism of Knallgasbacteria , 1972 .

[8]  D. Ramkrishna,et al.  Systematic development of hybrid cybernetic models: Application to recombinant yeast co‐consuming glucose and xylose , 2009, Biotechnology and bioengineering.

[9]  F. Srienc,et al.  Elementary mode analysis: a useful metabolic pathway analysis tool for characterizing cellular metabolism , 2009, Applied Microbiology and Biotechnology.

[10]  Georges Bastin,et al.  Dynamic metabolic modelling under the balanced growth condition , 2004 .

[11]  H. Schlegel,et al.  Verwertung von Fructose durch Hydrogenomonas H16 (I.) , 1964, Archiv für Mikrobiologie.

[12]  Jay D Keasling,et al.  Advanced biofuel production in microbes , 2010, Biotechnology journal.

[13]  D. Ramkrishna,et al.  Reduction of a set of elementary modes using yield analysis , 2009, Biotechnology and bioengineering.

[14]  E. Papoutsakis,et al.  A comparative view of metabolite and substrate stress and tolerance in microbial bioprocessing: From biofuels and chemicals, to biocatalysis and bioremediation. , 2010, Metabolic engineering.

[15]  A. Sinskey,et al.  Characterization of an extracellular lipase and its chaperone from Ralstonia eutropha H16 , 2013, Applied Microbiology and Biotechnology.

[16]  D. Ramkrishna,et al.  A hybrid model of anaerobic E. coli GJT001: Combination of elementary flux modes and cybernetic variables , 2008, Biotechnology progress.

[17]  Y. Schneider,et al.  Metabolic design of macroscopic bioreaction models: application to Chinese hamster ovary cells , 2006, Bioprocess and biosystems engineering.

[18]  A. Kienle,et al.  Experimental and theoretical analysis of poly (β-hydroxybutyrate) formation and consumption in Ralstonia eutropha , 2011 .

[19]  T. Bruno,et al.  Composition-Explicit Distillation Curves for Mixtures of Gasoline with Four-Carbon Alcohols (Butanols) , 2009 .

[20]  G. Stephanopoulos,et al.  Metabolic Engineering: Principles And Methodologies , 1998 .

[21]  Doraiswami Ramkrishna,et al.  On the Matching and Proportional Laws of Cybernetic Models , 2007, Biotechnology progress.

[22]  G. Stephanopoulos Metabolic fluxes and metabolic engineering. , 1999, Metabolic engineering.

[23]  Anthony J. Sinskey,et al.  Production of Poly(3-Hydroxybutyrate-co-3-Hydroxyhexanoate) from Plant Oil by Engineered Ralstonia eutropha Strains , 2011, Applied and Environmental Microbiology.

[24]  Stefan Schuster,et al.  Systems biology Metatool 5.0: fast and flexible elementary modes analysis , 2006 .

[25]  G. Bastin,et al.  FROM METABOLIC NETWORKS TO MINIMAL DYNAMIC BIOREACTION MODELS , 2007 .