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BIOMD0000000639 - Thiaville2016 - Wild type folate pathway model with proposed PanB reaction

 

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Reference Publication
Publication ID: 27065985
Thiaville JJ, Frelin O, García-Salinas C, Harrison K, Hasnain G, Horenstein NA, Díaz de la Garza RI, Henry CS, Hanson AD, de Crécy-Lagard V.
Experimental and Metabolic Modeling Evidence for a Folate-Cleaving Side-Activity of Ketopantoate Hydroxymethyltransferase (PanB).
Front Microbiol 2016; 7: 431
Department of Microbiology and Cell Science, University of Florida Gainesville, FL, USA.  [more]
Model
Original Model: BIOMD0000000639.origin
Submitter: Christopher Henry
Submission ID: MODEL1602280001
Submission Date: 28 Feb 2016 21:41:31 UTC
Last Modification Date: 01 Jun 2017 16:43:07 UTC
Creation Date: 03 Mar 2015 00:36:59 UTC
Encoders:  Christopher Henry
   Varun Kothamachu
set #1
bqbiol:hasProperty Gene Ontology folic acid biosynthetic process
Mathematical Modelling Ontology MAMO_0000046
set #2
bqbiol:hasTaxon Taxonomy Escherichia coli
Notes
Thiaville2016 - Wild type folate pathway model with proposed PanB reaction
This is a wild type E. coli model, and is one amongst the three models described in the paper. The other two models are MODEL1602280002 (wild type with PanB over expression) and MODEL1602280003 (wild type with PanB over expression and THF regulation). 

This model is described in the article:

Thiaville JJ, Frelin O, García-Salinas C, Harrison K, Hasnain G, Horenstein NA, Díaz de la Garza RI, Henry CS, Hanson AD, de Crécy-Lagard V.
Front Microbiol 2016; 7: 431

Abstract:

Tetrahydrofolate (THF) and its one-carbon derivatives, collectively termed folates, are essential cofactors, but are inherently unstable. While it is clear that chemical oxidation can cleave folates or damage their pterin precursors, very little is known about enzymatic damage to these molecules or about whether the folate biosynthesis pathway responds adaptively to damage to its end-products. The presence of a duplication of the gene encoding the folate biosynthesis enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (FolK) in many sequenced bacterial genomes combined with a strong chromosomal clustering of the folK gene with panB, encoding the 5,10-methylene-THF-dependent enzyme ketopantoate hydroxymethyltransferase, led us to infer that PanB has a side activity that cleaves 5,10-methylene-THF, yielding a pterin product that is recycled by FolK. Genetic and metabolic analyses of Escherichia coli strains showed that overexpression of PanB leads to accumulation of the likely folate cleavage product 6-hydroxymethylpterin and other pterins in cells and medium, and-unexpectedly-to a 46% increase in total folate content. In silico modeling of the folate biosynthesis pathway showed that these observations are consistent with the in vivo cleavage of 5,10-methylene-THF by a side-activity of PanB, with FolK-mediated recycling of the pterin cleavage product, and with regulation of folate biosynthesis by folates or their damage products.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 27065985 Submission Date: 28 Feb 2016 21:41:31 UTC Last Modification Date: 01 Jun 2017 16:43:07 UTC Creation Date: 03 Mar 2015 00:36:59 UTC
Mathematical expressions
Reactions
FolK FolP FolC GlyA
FolA PanB p-ABA_production H2-HMPt_production
THF_drain CH2-THF_drain    
Physical entities
Compartments Species
compartment H2-HMPt ATP H2-HMPterinPP
AMP p-ABA PPi
H2-Pteroate L-Glutamate Phosphate
ADP DHF L-serine
Glycine NADP NADPH
THF CH2-THF  
Reactions (10)
 
 FolK [ATP] + [H2-HMPt] → [AMP] + [H2-HMPterinPP];  
 
 FolP [p-ABA] + [H2-HMPterinPP] → [PPi] + [H2-Pteroate];  
 
 FolC [L-Glutamate] + [ATP] + [H2-Pteroate] → [DHF] + [ADP] + [Phosphate];  
 
 GlyA [THF] + [L-serine] ↔ [CH2-THF] + [Glycine];  
 
 FolA [DHF] + [NADPH] → [NADP] + [THF];  
 
 PanB [CH2-THF] → [H2-HMPt] + [p-ABA];  
 
 p-ABA_production  → [p-ABA];  
 
 H2-HMPt_production  → [H2-HMPt];  
 
 THF_drain [THF] → ;  
 
 CH2-THF_drain [CH2-THF] → ;  
 
Functions (2)
 
 Henri-Michaelis-Menten (irreversible) lambda(substrate, Km, V, V*substrate/(Km+substrate))
 
 Constant flux (irreversible) lambda(v, v)
 
 compartment Spatial dimensions: 3.0  Compartment size: 1.0
 
 H2-HMPt
Compartment: compartment
Initial concentration: 3.315E-6
 
 ATP
Compartment: compartment
Initial concentration: 0.0096
Constant
 
 H2-HMPterinPP
Compartment: compartment
Initial concentration: 1.0E-5
 
 AMP
Compartment: compartment
Initial concentration: 2.8E-4
Constant
 
 p-ABA
Compartment: compartment
Initial concentration: 1.0E-5
 
 PPi
Compartment: compartment
Initial concentration: 5.0E-4
Constant
 
 H2-Pteroate
Compartment: compartment
Initial concentration: 1.0E-5
 
 L-Glutamate
Compartment: compartment
Initial concentration: 8.46E-4
Constant
 
 Phosphate
Compartment: compartment
Initial concentration: 0.01
Constant
 
 ADP
Compartment: compartment
Initial concentration: 5.6E-4
Constant
 
 DHF
Compartment: compartment
Initial concentration: 1.0E-5
 
 L-serine
Compartment: compartment
Initial concentration: 6.8E-5
Constant
 
 Glycine
Compartment: compartment
Initial concentration: 2.77E-4
Constant
 
 NADP
Compartment: compartment
Initial concentration: 9.4E-7
Constant
 
 NADPH
Compartment: compartment
Initial concentration: 9.4E-7
Constant
 
 THF
Compartment: compartment
Initial concentration: 1.69E-4
 
 CH2-THF
Compartment: compartment
Initial concentration: 8.47E-5
 
FolK (1)
 
   k1
Value: 15.8
Constant
 
FolP (1)
 
   k1
Value: 4000.0
Constant
 
FolC (1)
 
   k1
Value: 6184.0
Constant
 
GlyA (2)
 
   k1
Value: 4080.0
Constant
 
   k2
Value: 2000.0
Constant
 
FolA (1)
 
   k1
Value: 31170.0
Constant
 
PanB (1)
 
   k1
Value: 0.004
Constant
 
p-ABA_production (1)
 
   v
Value: 1.66E-7
Constant
 
H2-HMPt_production (1)
 
   v
Value: 1.66E-7
Constant
 
THF_drain (2)
 
   Km
Value: 1.571E-4
Constant
 
   V
Value: 1.243E-7
Constant
 
CH2-THF_drain (2)
 
   Km
Value: 5.921E-5
Constant
 
   V
Value: 1.726E-7
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000639

Curator's comment: (updated: 01 Jun 2017 17:42:23 BST)

This is a wild type E. coli model, and is one amongst three models described in the paper. This model was not curated as it does not have a corresponding simulation figure in the paper for validation.

Please refer to the other two models MODEL1602280002 (wild type with PanB over expression) and MODEL1602280003 (wild type with PanB over expression and THF regulation) for curation and validation.

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