Hermansen2015 - denovo biosynthesis of pyrimidines in yeast

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Model Identifier
BIOMD0000000590
Short description
Hermansen2015 - denovo biosynthesis of pyrimidines in yeast

This model is described in the article:

Hermansen RA , Mannakee BK , Knecht W , Liberles DA , Gutenkunst RN
BMC Evolutionary Biology. 2015, 15:232

Abstract:

Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine biosynthesis in the yeast Saccharomyces cerevisiae to relate pathway function to selective pressures on individual protein-encoding genes.Gene families across yeast were constructed for each member of the pathway and the ratio of nonsynonymous to synonymous nucleotide substitution rates (dN/dS) was estimated for each enzyme from S. cerevisiae and closely related species. We found a positive relationship between the influence that each enzyme has on pathway function and its selective constraint.We expect this trend to be locally present for enzymes that have pathway control, but over longer evolutionary timescales we expect that mutation-selection balance may change the enzymes that have pathway control.

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Format
SBML (L2V4)
Related Publication
  • Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast.
  • Hermansen RA, Mannakee BK, Knecht W, Liberles DA, Gutenkunst RN
  • BMC evolutionary biology , 0/ 2015 , Volume 15 , pages: 232 , PubMed ID: 26511837
  • Department of Biology and Center for Computational Genetics and Genomics, Temple University, Philadelphia, PA, 19122, USA. rhermans@uwyo.edu.
  • Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine biosynthesis in the yeast Saccharomyces cerevisiae to relate pathway function to selective pressures on individual protein-encoding genes.Gene families across yeast were constructed for each member of the pathway and the ratio of nonsynonymous to synonymous nucleotide substitution rates (dN/dS) was estimated for each enzyme from S. cerevisiae and closely related species. We found a positive relationship between the influence that each enzyme has on pathway function and its selective constraint.We expect this trend to be locally present for enzymes that have pathway control, but over longer evolutionary timescales we expect that mutation-selection balance may change the enzymes that have pathway control.
Contributors
Brian Mannakee

Metadata information

is
BioModels Database MODEL1512160000
BioModels Database BIOMD0000000590
isDescribedBy
encodes
KEGG Pathway Pyrimidine metabolism

Curation status
Curated

Tags
Name Description Size Actions

Model files

BIOMD0000000590_url.xml SBML L2V4 representation of Hermansen2015 - denovo biosynthesis of pyrimidines in yeast 75.68 KB Preview | Download

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  • Model originally submitted by : Brian Mannakee
  • Submitted: Dec 16, 2015 4:08:30 PM
  • Last Modified: Feb 16, 2016 4:58:21 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Feb 16, 2016 4:58:21 PM
    • Submitted by: Brian Mannakee
    • With comment: Current version of Hermansen2015 - denovo biosynthesis of pyrimidines in yeast
  • Version: 1 public model Download this version
    • Submitted on: Dec 16, 2015 4:08:30 PM
    • Submitted by: Brian Mannakee
    • With comment: Original import of Hermansen2015_denovo_pyrimidine_biosynthesis

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
cp

Carbamoyl phosphate ; carbamoyl phosphate
3.7E-4 mmol
ca

N-Carbamoyl-L-aspartate ; N-carbamoyl-L-aspartic acid
3.7E-4 mmol
omp

Orotidine 5'-phosphate ; orotidine 5'-phosphate
3.7E-4 mmol
ump

UMP ; UMP
3.7E-4 mmol
udp

UDP ; UDP
0.002886 mmol
utp

UTP ; UTP
0.00666 mmol
ctp

CTP ; CTP
3.7E-4 mmol
dho

(S)-Dihydroorotate ; (S)-dihydroorotic acid
3.7E-4 mmol
Reactions
Reactions Rate Parameters
cp => ca; utp, cp, utp compartment*vmax2*cp*asp/((1+utp/K_utp)*(K_m2+cp)*(K_asp+asp))/compartment K_asp = 0.168308889432487; vmax2 = 2.44590712912244; K_m2 = 2.00489353757245; asp = 0.0972544685826559; K_utp = 1.413855257896
cp => ; cp compartment*d*cp/compartment d = 0.1
ca => dho; ca compartment*vmax3*ca/(K_m3+ca)/compartment vmax3 = 28.6613123782585; K_m3 = 1.27179181717468
ca => ; ca compartment*d*ca/compartment d = 0.1
omp => ; omp compartment*d*omp/compartment d = 0.1
ump => udp; ump compartment*vmax10*ump/(K_m10+ump)/compartment vmax10 = 6.55543523218919; K_m10 = 0.0267841313759584
udp => utp; udp compartment*vmax7*udp/(K_m7+udp)/compartment K_m7 = 0.166382738667754; vmax7 = 5.83104141997666
utp => ; utp compartment*d*utp/compartment d = 0.1
ctp => ; ctp compartment*g_pyr*ctp/(K_Mp+ctp)/compartment K_Mp = 5.48714446027226; g_pyr = 0.198306450999093
dho => oro; dho compartment*vmax4*dho/(K_m4+dho)/compartment K_m4 = 0.0160033122150611; vmax4 = 91.7802875108298
dho => ; dho compartment*d*dho/compartment d = 0.1
Curator's comment:
(added: 16 Feb 2016, 16:43:39, updated: 16 Feb 2016, 16:43:39)
There are no simulation plots in the paper, so Table 3, which is the steady-state concentrations of the metabolites has been reproduced here. The stead-state concentrations were calculated using Copasi v4.15 (Build 95).