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BIOMD0000000017 - Hoefnagel2002_PyruvateBranches

 

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Reference Publication
Publication ID: 11932446
Hoefnagel MH, Starrenburg MJ, Martens DE, Hugenholtz J, Kleerebezem M, Van Swam II, Bongers R, Westerhoff HV, Snoep JL.
Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis.
Microbiology (Reading, Engl.) 2002 Apr; 148(Pt 4): 1003-1013
Wageningen Centre for Food Sciences and Food and Bioprocess Engineering Group, Wageningen University, PO Box 8129, 6700 EV Wageningen, The Netherlands. marcel.hoefnagel@algemeen.pk.wau.nl  [more]
Model
Original Model: BIOMD0000000017.xml.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL6617235316
Submission Date: 13 Sep 2005 13:14:15 UTC
Last Modification Date: 04 Apr 2014 14:23:02 UTC
Creation Date: 06 Mar 2005 20:03:34 UTC
Encoders:  Nicolas Le Novère
   Maria Schilstra
set #1
bqbiol:hasTaxon Taxonomy Lactococcus lactis
bqbiol:isPartOf KEGG Pathway map00650
KEGG Pathway map00620
bqbiol:isVersionOf Gene Ontology lactate metabolic process
Gene Ontology pyruvate metabolic process
Gene Ontology organic acid metabolic process
set #2
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
Notes

This a model from the article:
Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis.
Hoefnagel MH, Starrenburg MJ, Martens DE, Hugenholtz J, Kleerebezem M, Van Swam II, Bongers R, Westerhoff HV, Snoep JL Microbiology2002 Apr; 148(4):1003-13 11932446,
Abstract:
Everyone who has ever tried to radically change metabolic fluxes knows that it is often harder to determine which enzymes have to be modified than it is to actually implement these changes. In the more traditional genetic engineering approaches ’bottle-necks’ are pinpointed using qualitative, intuitive approaches, but the alleviation of suspected ’rate-limiting’ steps has not often been successful. Here the authors demonstrate that a model of pyruvate distribution in Lactococcus lactis based on enzyme kinetics in combination with metabolic control analysis clearly indicates the key control points in the flux to acetoin and diacetyl, important flavour compounds. The model presented here (available at http://jjj.biochem.sun.ac.za/wcfs.html) showed that the enzymes with the greatest effect on this flux resided outside the acetolactate synthase branch itself. Experiments confirmed the predictions of the model, i.e. knocking out lactate dehydrogenase and overexpressing NADH oxidase increased the flux through the acetolactate synthase branch from 0 to 75% of measured product formation rates.

The paper does not have any figure to be put as a curation figure in the BioModels database. The model does reproduce the fluxes and control-coefficients given in Figure 2 and Table 4. To reproduce the results, the model was changed from the description in the article according to the model on JWS: the parameter Kmpyr was changed to 2.5 from 25. The equillibrium constant for PTA reaction (R4) was changed from 0.0281 to 0.0065. The Km for oxygen in the NOX reaction (R13) was changed from 0.01 to 0.2. Slight deviations between the values in the article and the model results may stem from different algorithms used for finding the steady state.

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 11932446 Submission Date: 13 Sep 2005 13:14:15 UTC Last Modification Date: 04 Apr 2014 14:23:02 UTC Creation Date: 06 Mar 2005 20:03:34 UTC
Mathematical expressions
Reactions
R1 R2 R3 R4
R5 R6 R7 R8
R9 R10 R11 R12
R13 R14    
Physical entities
Compartments Species
compartment ADP NAD ATP
NADH pyruvate lactate
CoA halfglucose AcCoA
AcP Ac AcO
EtOH AcLac AcetoinIn
AcetoinOut Butanediol O2
PO4    
Reactions (14)
 
 R1 [ADP] + [NAD] + [halfglucose] → [ATP] + [NADH] + [pyruvate];  
 
 R2 [NADH] + [pyruvate] → [NAD] + [lactate];  
 
 R3 [NAD] + [pyruvate] + [CoA] → [NADH] + [AcCoA];  
 
 R4 [AcCoA] + [PO4] → [CoA] + [AcP];  
 
 R5 [ADP] + [AcP] → [ATP] + [Ac];  
 
 R6 [NADH] + [AcCoA] → [NAD] + [CoA] + [AcO];  
 
 R7 [NADH] + [AcO] → [NAD] + [EtOH];  
 
 R8 2.0 × [pyruvate] → [AcLac];  
 
 R9 [AcLac] → [AcetoinIn];  
 
 R10 [AcetoinIn] → [AcetoinOut];  
 
 R11 [NADH] + [AcetoinIn] → [NAD] + [Butanediol];  
 
 R12 [ATP] → [ADP];  
 
 R13 [NADH] + [O2] → [NAD];  
 
 R14 [AcLac] → [AcetoinIn];  
 
   Spatial dimensions: 3.0  Compartment size: 1.0
 
 ADP
Compartment: compartment
Initial amount: 4.9
 
 NAD
Compartment: compartment
Initial amount: 6.33
 
 ATP
Compartment: compartment
Initial amount: 0.1
 
 NADH
Compartment: compartment
Initial amount: 3.67
 
 pyruvate
Compartment: compartment
Initial amount: 1.0
 
 lactate
Compartment: compartment
Initial amount: 0.1
 
 CoA
Compartment: compartment
Initial amount: 1.0
 
   halfglucose
Compartment: compartment
Initial amount: 30.0
 
 AcCoA
Compartment: compartment
Initial amount: 0.0
 
 AcP
Compartment: compartment
Initial amount: 0.0
 
 Ac
Compartment: compartment
Initial amount: 1.0
 
 AcO
Compartment: compartment
Initial amount: 0.0
 
 EtOH
Compartment: compartment
Initial amount: 1.0
 
 AcLac
Compartment: compartment
Initial amount: 0.0
 
 AcetoinIn
Compartment: compartment
Initial amount: 0.0
 
 AcetoinOut
Compartment: compartment
Initial amount: 0.0
 
 Butanediol
Compartment: compartment
Initial amount: 0.01
 
 O2
Compartment: compartment
Initial amount: 0.2
 
 PO4
Compartment: compartment
Initial amount: 10.0
Constant
 
R1 (7)
 
   V_1
Value: 2397.0
Constant
 
   Kglc_1
Value: 0.1
Constant
 
   Knad_1
Value: 0.1412
Constant
 
   Kadp_1
Value: 0.04699
Constant
 
   Kpyr_1
Value: 2.5
Constant
 
   Knadh_1
Value: 0.08999
Constant
 
   Katp_1
Value: 0.01867
Constant
 
R2 (6)
 
   V_2
Value: 5118.0
Constant
 
   Keq_2
Value: 21120.69
Constant
 
   Kpyr_2
Value: 1.5
Constant
 
   Knadh_2
Value: 0.08
Constant
 
   Klac_2
Value: 100.0
Constant
 
   Knad_2
Value: 2.4
Constant
 
R3 (7)
 
   V_3
Value: 259.0
Constant
 
   Kpyr_3
Value: 1.0
Constant
 
   Knad_3
Value: 0.4
Constant
 
   Kcoa_3
Value: 0.014
Constant
 
   Ki_3
Value: 46.4159
Constant
 
   Knadh_3
Value: 0.1
Constant
 
   Kaccoa_3
Value: 0.0080
Constant
 
R4 (8)
 
   V_4
Value: 42.0
Constant
 
   Keq_4
Value: 0.0065
Constant
 
   Kiaccoa_4
Value: 0.2
Constant
 
   Kpi_4
Value: 2.6
Constant
 
   Kipi_4
Value: 2.6
Constant
 
   Kiacp_4
Value: 0.2
Constant
 
   Kicoa_4
Value: 0.029
Constant
 
   Kacp_4
Value: 0.7
Constant
 
R5 (6)
 
   V_5
Value: 2700.0
Constant
 
   Keq_5
Value: 174.217
Constant
 
   Kadp_5
Value: 0.5
Constant
 
   Kacp_5
Value: 0.16
Constant
 
   Kac_5
Value: 7.0
Constant
 
   Katp_5
Value: 0.07
Constant
 
R6 (7)
 
   V_6
Value: 97.0
Constant
 
   Keq_6
Value: 1.0
Constant
 
   Kaccoa_6
Value: 0.0070
Constant
 
   Knadh_6
Value: 0.025
Constant
 
   Knad_6
Value: 0.08
Constant
 
   Kcoa_6
Value: 0.0080
Constant
 
   Kaco_6
Value: 10.0
Constant
 
R7 (6)
 
   V_7
Value: 162.0
Constant
 
   Keq_7
Value: 12354.9
Constant
 
   Kaco_7
Value: 0.03
Constant
 
   Knadh_7
Value: 0.05
Constant
 
   Knad_7
Value: 0.08
Constant
 
   Ketoh_7
Value: 1.0
Constant
 
R8 (5)
 
   V_8
Value: 600.0
Constant
 
   Kpyr_8
Value: 50.0
Constant
 
   Keq_8
Value: 9.0E12
Constant
 
   Kaclac_8
Value: 100.0
Constant
 
   n_8
Value: 2.4
Constant
 
R9 (3)
 
   V_9
Value: 106.0
Constant
 
   Kaclac_9
Value: 10.0
Constant
 
   Kacet_9
Value: 100.0
Constant
 
R10 (2)
 
   V_10
Value: 200.0
Constant
 
   Kacet_10
Value: 5.0
Constant
 
R11 (6)
 
   V_11
Value: 105.0
Constant
 
   Keq_11
Value: 1400.0
Constant
 
   Kacet_11
Value: 0.06
Constant
 
   Knadh_11
Value: 0.02
Constant
 
   Kbut_11
Value: 2.6
Constant
 
   Knad_11
Value: 0.16
Constant
 
R12 (3)
 
   V_12
Value: 900.0
Constant
 
   Katp_12
Value: 6.196
Constant
 
   n_12
Value: 2.58
Constant
 
R13 (4)
 
   V_13
Value: 118.0
Constant
 
   Knadh_13
Value: 0.041
Constant
 
   Ko_13
Value: 0.2
Constant
 
   Knad_13
Value: 1.0
Constant
 
R14 (1)
 
   k_14
Value: 3.0E-4
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000017

Curator's comment: (updated: 28 Nov 2010 23:38:12 GMT)

Results of the model at steady state. Steady state and metabolic control analysis were performed using Copasi 4.6

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