JWS Online

fung1

 Simulate
 Download
 Create derivative

Model

fung1

The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000067) Biomodels notes: A Synthetic Gene-Metabolic Oscillator Reference: Fung et al; Nature (2005) 435:118-122 Name of kinetic law Reaction Glycolytic flux, V_gly: nil -> AcCoA; Flux to TCA cycle/ETOH, V_TCA: AcCoA -> TCA/EtOH; HOAc ex/import,reversible, V_out: HOAc -> HOAc_E V_Pta: AcCoA + Pi -> AcP + CoA reversible, V_Ack: AcP + ADP -> OAc + ATP V_Acs: OAC + ATP -> AcCoA +PPi Acetic acid-base equillibrium, reversible, V_Ace: OAC + H -> HOAc Expression of LacI, R_LacI: nil -> LacI Expression of Acs, R_Acs: nil -> Acs Expression of Pta, R_Pta: nil -> Pta LacI degradation, R_dLacI: LacI -> nil Acs degradation, R_dAcs: Acs -> nil Pta degradation, R_dPta: Pta -> nil For this model the differential equation for V_Ace was changed from: C*(AcP*H-K_eq*OAC) with C = 100 in the supplemental material to C*(OAc*H-K_eq*HOAc) with C = 100, as in Bulter et. al; PNAS(2004),101,2299-2304 , and a value for K_eq of 5*10^-4 after communication with the authors. translated to SBML by: Lukas Endler(luen at tbi.univie.ac.at), Christoph Flamm (xtof at tbi.univie.ac.at) Biomodels Curation The model reproduces 3a of the paper for glycolytic flux Vgly = 0.5. The authors have agreed that the values on Y-axis are marked wrong and hence there is a discrepancy between model simulation results and the figure. Also, note that the values of concentration and time are in dimensionless units. The model was successfully tested on MathSBML and Jarnac. JWS Online curation: This model was curated by reproducing the figures 3A of the paper for glycolytic flux Vgly = 0.5, Vgly = 0.05, Vgly = 0.01 and Vgly = 0.001

None

None

None

None

None

None

Manuscript information

A synthetic gene-metabolic oscillator.

  • Eileen Fung
  • Wilson W Wong
  • Jason K Suen
  • Thomas Bulter
  • Sun-gu Lee
  • James C Liao
Nature 2005; 435 (7038): 118-122
Abstract
Autonomous oscillations found in gene expression and metabolic, cardiac and neuronal systems have attracted significant attention both because of their obvious biological roles and their intriguing dynamics. In addition, de novo designed oscillators have been demonstrated, using components that are not part of the natural oscillators. Such oscillators are useful in testing the design principles and in exploring potential applications not limited by natural cellular behaviour. To achieve transcriptional and metabolic integration characteristic of natural oscillators, here we designed and constructed a synthetic circuit in Escherichia coli K12, using glycolytic flux to generate oscillation through the signalling metabolite acetyl phosphate. If two metabolite pools are interconverted by two enzymes that are placed under the transcriptional control of acetyl phosphate, the system oscillates when the glycolytic rate exceeds a critical value. We used bifurcation analysis to identify the boundaries of oscillation, and verified these experimentally. This work demonstrates the possibility of using metabolic flux as a control factor in system-wide oscillation, as well as the predictability of a de novo gene-metabolic circuit designed using nonlinear dynamic analysis.

Unit definitions 0

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition

Compartments 1

Id Name Spatial dimensions Size
compartment Intracellular 3.0 1.0

Species 8

Id Name Initial quantity Compartment Fixed
AcCoA Acetyl-CoA 0.0 compartment (Intracellular) ✘
AcP Acetyl phosphate 0.0 compartment (Intracellular) ✘
Acs Acetyl-CoA synthase 0.0 compartment (Intracellular) ✘
HOAc protonated acetate 0.0 compartment (Intracellular) ✘
HOAc_E acetate export 0.0 compartment (Intracellular) ✔
LacI lac repressor 0.0 compartment (Intracellular) ✘
OAc Acetate 0.0 compartment (Intracellular) ✘
Pta Phosphate acetyl transferase 0.0 compartment (Intracellular) ✘

Initial assignments 0

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Reactions 13
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
R_Acs Acetyl-CoA synthase synthesis ∅ > Acs

compartment * (alpha2 * pow(AcP / Kg2, n) / (1 + pow(AcP / Kg2, n)) + alpha0)
R_LacI LacI synthesis ∅ > LacI

compartment * (alpha1 * pow(AcP / Kg1, n) / (1 + pow(AcP / Kg1, n)) + alpha0)
R_Pta Phosphate acetyl transferase synthase ∅ > Pta

alpha3 / (1 + pow(LacI / Kg3, n)) + alpha0
R_dAcs Acs degradation Acs > ∅

compartment * kd * Acs
R_dLacI LacI degradation LacI > ∅

compartment * kd * LacI
R_dPta Pta degradation Pta > ∅

compartment * kd * Pta
V_Ace Acid-base equilibrium OAc = HOAc

compartment * C * (OAc * H - Keq * HOAc)
V_Ack Acetate kinase AcP = OAc

compartment * (kAck_f * AcP - kAck_r * OAc)
V_Acs Acetyl-CoA synthase flux OAc > AcCoA

compartment * k2 * Acs * OAc / (KM2 + OAc)
V_Pta Phosphate acetyl transferase flux AcCoA > AcP

compartment * k1 * Pta * AcCoA / (KM1 + AcCoA)
V_TCA Flux to TCA cycle AcCoA > ∅

compartment * kTCA * AcCoA
V_gly Glycolytic flux ∅ > AcCoA

compartment * S0
V_out Intercellular transport of Acetate HOAc = HOAc_E

compartment * k3 * (HOAc - HOAc_E)

Parameters 0   21

Global parameters

Id Value
C 100.0
H 0.0000001
KM1 0.06
KM2 0.1
Keq 0.0005
Kg1 10.0
Kg2 10.0
Kg3 0.001
S0 0.5
alpha0 0.0
alpha1 0.1
alpha2 2.0
alpha3 2.0
k1 80.0
k2 0.8
k3 0.01
kAck_f 1.0
kAck_r 1.0
kTCA 10.0
kd 0.06
n 2.0

Local parameters

Id Value Reaction

Rules 0   0   0

Assignment rules

Definition

Rate rules

Definition

Algebraic rules

Definition

Events 0

Trigger Assignments