Table 2. Parameter values and descriptions for all parameters used in model A.
| Parameter | Value | Units | Description | Source |
|---|---|---|---|---|
| U1 | 2.66E-01 | M-1s-1 | Maximum uptake rate (Vmax) of eGlc | Fitted from a known value of Ks [92] and data on E. coli growth dynamics [93] (S13 Fig). |
| M1 | 2.69E-04 | s-1 | Rate of dGTP synthesis from iGlc | This value was fitted to published data on E. coli growth dynamics [93] (S13 Fig). |
| Ks | 3.97E-05 | M | Michaelis Menten constant Ks: Concentration of glucose at which glucose uptake rate of 1/2 Vmax is achieved | Ks measured as 7.16 μg/ml by [92]. |
| I1 | 6.90E-03 | s-1 | Rate of dGTP incorporation into DNA opposite C | Fitted to give known cytoplasmic concentration dGTP in exponential growth phase E. coli of 92 μm in 0.4% glucose [94]. |
| D1 | 6.90E-03 | s-1 | Rate of C pairing opposite incorporated G | Given the same value as I1 as the synthesis of new DNA (DNA) and new genomes (wtCell) should generally proceed at equal rates (this is violated during rapid exponential growth [95] but not included in this model). |
| O2 | 12.0 | M-1s-1 | Rate of dGTP oxidation to odGTP by ROS | Selected to give a mutation rate of 1.94 × 10-10 base pair substitutions per nucleotide in 0.2% glucose minimal media [26]. |
| I2 | 2.53E-04 | s-1 | Rate of odGTP incorporation into DNA opposite adenine | The relative efficiency of odGTP binding to A (I2) compared to G binding to C (I1) is 7.7 × 10-8: 2.1 × 10-6 (20), therefore, I2 = I1 * (7.7 × 10-8/2.1 × 10-6). |
| D2 | 2.00E-04 | s-1 | Rate of C pairing opposite incorporated oG causing an AT>CG mutation | Rate of C pairing opposite an odGTP (D2) relative to CG (I1 and D1) is 6 × 10-8: 2.1 × 10-6 (20). |
| C1 | 2.8 | s-1 | Rate of odGTP hydrolysis to odGMP by nudix hydrolase enzyme MutT (NudA) | Value taken from Kcat of MutT measured in vitro [96]. |
| C2 | 3.50E-04 | s-1 | Rate of removal of adenine base incorporated opposite 8-oxodG in the genome by enzyme MutY | Value taken from Kcat of MutY measured in vitro as 0.021 min-1 = 3.5 × 10-4 sec-1 ([97]). |
| R1 | 2.00E-04 | s-1 | Rate of oG insertion into DNA opposite cytosine | Relative incorporation efficiency opposite C of odGTP:dGTP (R1) is 0.029 (20)‚ therefore, R1 = I1 * 0.029. |
| S | 2.58E-02 | s-1 | Rate of removal of adenine base incorporated opposite 8-oxodG in the genome by enzyme MutS | Fitted to known rate of mutation in mutS knockout of 40× wild type [98]. |
| r | 17.3 | s-1 | Rate of ROS production from iGlc relative to dGTP production rate | Selected to give a known H2O2 production rate of 14 μm/second in 0.2% glucose minimal media normalised to cell volume [32]. |
| O3 | 5.60E+01 | s-1 | Rate of ROS degradation through reactions other than dGTP oxidation. Primarily AhpCF/KatEG enzyme activity. | Fitted to give a standing ROS concentration of 1.9 × 10-7 M, midpoint of known 1.3 × 10-7 - 2.5 × 10-7 M in LB [23]. |
| R2 | 2.53E-04 | s-1 | Rate of adenine pairing opposite incorporated oG | The relative efficiency of odGTP binding to A (R2) compared to G binding to C (I1) is 7.7 × 10-8: 2.1 × 10-6 (20), therefore, R2 = I1 * (7.7 × 10-8/2.1 × 10-6). |
| Met1 | 1,545 | s-1 | Stoichiometry of glucose conversion to dGTP for genome building (i.e., how many molecules of glucose are needed to produce 1 molecule of dGTP) | Fitted to published data from [3] of cell density as a product of glucose concentration (S14 Fig). |
| CellVol | 1.03E-12 | ml | Volume of one E. coli cell in minimal media growing in exponential phase | Mean value of 4 estimates of cell volume in exponential phase cells grown in minimal M9 media [83]. |
| molML | 6.02E+20 | molecules | Number of molecules per mL in a 1 M solution | One thousandth of Avogadro’s constant (NA). |
| GCperGen | 2357528 | GC basepairs | Number of GC basepairs per genome | E. coli Strain MG1655, EBI Accession U00096.3 |
eGlc, external glucose concentration; ROS reactive oxygen species.