Geranyl diphosphate synthase (GPPS)
You can go back to main page of the kinetic model here.
Contents
About GPPS
Geranyl diphosphate synthase (GPPS) catalyzes the formation of geranyl diphosphate (GPP) from two universal terpene precursors -- Isopentenyl diphosphate (IPP) and Dimethylallyl diphosphate (DMAPP). IPP and DMAPP can be produced from the mevalonate (MEV) or non-mevalonate (with Methylerithritol phosphate (MEP) as intermdeiate) pathway. The synthesis of GPP is essential in our engineered network as it is the sole precursor for the production of limonene, which is the main precursor for all of our monoterpenes of interest.
Reaction catalysed
Metabolite and Enzyme Background Information
Long metabolite names are abbreviated in the model for clarity and standard identification purposes.
Metabolite | Abbreviation | Chemical Formula | Molar mass (g/mol) | ChEBI | ChEMBL | PubChem | MetaCyc | BRENDA |
---|---|---|---|---|---|---|---|---|
dimethylallyl diphosphate | DMAPP | |||||||
isopentenyl diphosphate | IPP | |||||||
geranyl diphosphate | GPP | C10H20O7P2 | 314.209 | 17211 | 41432 | 445995 | ||
diphosphate | PP | O7P2 | 173.94 | 644102 | ||||
geranyl diphosphate synthase | GPPS | 32.16 kD (from nucleotide sequence), 36 kD (experimental) | CPLX-8656 | 2.5.1.1 |
Equation Rate
Parameter | Description |
---|---|
VGPPS | Reaction rate for Geranyl diphosphate synthase |
Vmaxforward | Maximum reaction rate towards the production of GPP |
KmGPP | Michaelis-Menten constant for GPP |
KmIPP | Michaelis-Menten constant for IPP |
KmPP | Michaelis-Menten constant for PP |
KmDMAPP | Michaelis-Menten constant for DMAPP |
Keq | Equilibrium constant |
[GPP] | GPP concentration |
[DMAPP] | DMAPP concentration |
[IPP] | DMAPP concentration |
[PP] | PP concentration |
Strategies for estimating the kinetic parameter values
Calculating the Equilibrium Constant
Standard Gibbs Free energy for GPPS from MetaCyc is -13.0 kcal mol-1.
The equilibrium constant can be calculated using the Van't Hoff Isotherm equation:
Failed to parse (Cannot store math image on filesystem.): = exp \left ( \cfrac {-(-13.0 \text { kcalmol}^{-1})}{ (1.98722 \text{ calK}^{-1} \text { mol}^{-1} * 289 K} \right )
Failed to parse (Cannot store math image on filesystem.): = exp \left ( \cfrac {13.0 \text { kcalmol}^{-1} }{ 574.30658 \text{ calK}^{-1}\text { mol}^{-1} }\right)
Failed to parse (Cannot store math image on filesystem.): = exp \left ( \cfrac{ 13000 \text {calmol}^{-1}}{574.30658 \text{ cal}\text { mol}^{-1}} \right)
Failed to parse (Cannot store math image on filesystem.): = 6788526395
where;
Keq | Equilibrium constant |
-?G° | Gibbs free energy change. For GPPS it is -13.0 kcalmol-1 |
R | Gas constant with a value of 1.98722 calK-1mol-1 |
T | Temperature which is always expressed in kelvin, as a standard, I used 298 K |
Published Kinetic Parameter Values
Values for the kinetic parameter required to simulate this model can be obtained from published and unpublished literature.
A more detailed descriptions of the values listed above can be found HERE , where I've linked and highlighted where these data came from.
Substrate, Product & Enzyme Concentration Values
Concentration | Unit | Substrate / Product | Directionality | Organism | References |
---|---|---|---|---|---|
15 | µM | IPP | forward | Phaedon cochleariae | [1] |
50 | µM | DMAPP | forward | Phaedon cochleariae | [1] |
50 | µM | DMAPP | forward | Phaedon cochleariae | [1] |
50 | µM | IPP | forward | Phaedon cochleariae | [1] |
250 | µM | IPP | forward | Picea abies | [2] |
800 | µM | DMAPP | forward | Picea abies | [2] |
Km Values
Km (mM) | Unit | Substrate / Product | Directionality | Organism | References |
---|---|---|---|---|---|
81 | μM | DMAPP | forward | Mentha sp. | [3] |
88 | μM | IPP | forward | Mentha sp. | [3] |
241 | μM | DMAPP | forward | Mentha sp. | [3] |
215 | μM | DMAPP | forward | Mentha sp. | [3] |
44 | μM | IPP | forward | Abies grandis | [4] |
55 | μM | IPP | forward | Abies grandis | [4] |
44 | μM | IPP | forward | Abies grandis | [4] |
163 | μM | DMAPP | forward | Abies grandis | [4] |
90 | μM | DMAPP | forward | Abies grandis | [4] |
82 | μM | DMAPP | forward | Abies grandis | [4] |
0.84 | μM | IPP | forward | Phaedon cochleariae | [1] |
11.6 | μM | DMAPP | forward | Phaedon cochleariae | [1] |
1103 | μM | DMAPP | forward | Phaedon cochleariae | [1] |
11.79 | μM | IPP | forward | Phaedon cochleariae | [1] |
58 | μM | DMAPP | forward | Mycobacterium tuberculosis | [5] |
163 | μM | IPP | forward | Mycobacterium tuberculosis | [5] |
390 | μM | DMAPP | forward | Picea abies | [2] |
170 | μM | IPP | forward | Picea abies | [2] |
Vmax values
Vmax | Unit | Directionality | Organism | References |
---|---|---|---|---|
0.44 | µmol/min/mg (unit) | forward | Phaedon cochleariae | [1] |
0.67 | µmol/min/mg (unit) | forward | Phaedon cochleariae | [1] |
2.39 | µmol/min/mg (unit) | forward | Phaedon cochleariae | [1] |
0.17 | µmol/min/mg (unit) | forward | Phaedon cochleariae | [1] |
4.2 | nkat/mg | forward | Picea abies | [2] |
Kcat values
Kcat | Unit | Organism | Reference |
---|---|---|---|
0.7 | min-1 | Mycobacterium tuberculosis | [5] |
5.1 | min-1 | Mycobacterium tuberculosis | [5] |
1.4 | s-1 | Picea abies | [2] |
1.8 | s-1 | Abies grandis | [4] |
0.5 | s-1 | Abies grandis | [4] |
1.6 | s-1 | Abies grandis | [4] |
Extracting Information from (INSERT SUBSTRATE/PRODUCT) Production Rates
Amount produced (mg/L) | Time (H) | Organism | Description | Reaction Flux (µM/s) |
---|---|---|---|---|
X | X | Y | Z | Z |
X | X | Y | Z | Z |
X | X | Y | Z | Z |
X | X | Y | Z | Z |
X | X | Y | Z | Z |
X | X | Y | Z | Z |
Simulations
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Frick, S. 2013. "Metal ions control product specificity of isoprenyl diphosphate synthases in the insect terpenoid pathway", PNAS, 110(11):4194-4199 Cite error: Invalid
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tag; name "Frick2013" defined multiple times with different content - ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Schmidt, A. 2010. "A bifunctional geranyl and geranylgeranyl diphosphate synthase is involved in terpene oleoresin formation in Picea abies", Plant Physiology, 152:639-655
- ↑ 3.0 3.1 3.2 3.3 Burke, C. 2004. "Heteromeric geranyl diphosphate synthase from mint: construction of a functional fusion protein and inhibition by biphosphonate substrate analogs", Archives of Biochemistry and Biophysics, 422:52-60
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Burke, C. 2002. "Geranyl diphosphate synthase from Abies grandis:cDNA isolation, functional expression, and characterization", Archives of Biochemistry and Biophysics, 405:130-136
- ↑ 5.0 5.1 5.2 5.3 Mann, F.M. 2011. "Rv0989c encodes a novel (E)-geranyl diphosphate synthase facilitating decaprenyl diphosphate biosynthesis in Mycobacterium tuberculosis", FEBS Letters, 585(3):549-554