Designing novel cellulase systems through agent-based modeling and global sensitivity analysis

Figures & data

Figure 1. Diagram showing the steps of an ABM simulation.

Figure 2. Number of iterations required for cellulose hydrolysis and sugar consumption for 200 independent simulations given bacteria cell density values ranging between 10 and 100 cells per simulation. Large variance was calculated at low cell densities.

Figure 3. Variance of cellulose hydrolysis and sugar consumption over 200 iterations as a function of the bacteria cell density (number of cells) for the three different cellulase enzyme expression systems.

Table 2. The t test results comparing cellulase expression systems

t test Results
Parameter	Value	Parameter	Value
Mean Non-complexed	280.0	Mean Complexed	188.0
Mean Complexed	188.0	Mean Hybrid	190.3
n Non-complexed	200	n Complexed	200
n Complexed	200	n Hybrid	200
df	392.4	df	381.4
α	0.05	α	0.05
t Calculated	13.1	t Calculated	-0.3
t α/2 critical	2.0	t α/2 critical	2.0

Figure 4. Iterations required for changing ratios of exoglucanase and endoglucanase at constant β-glucosidase.

Figure 5. First-order indices of the GSA for parameters listed in Table 1.

Figure 6. Total effect indices of the GSA for parameters listed in Table 1.

Table 3. Number of articles published (as of January 2012) on topics related to improving a CBP

Search Query (PUBMED)	Articles Published
Enzyme engineering	41 210
Improving glucose/substrate uptake rate	246/22
Bioreactor cell density	1386
Cellulase enzyme systems	7666

Table 1. ABM parameters, bounds, and descriptions

Parameter	Lower Bound	Upper Bound	Function
EnzymeProductionRate	1	100	Determines the rate of cellulase enzyme production in the non-complexed system
EnzymeProductionRateH	0.1	10	Determines the rate of cellulase enzyme production in the hybrid model
CompositionExo	0	100	Selects the composition of exoglucanase
CompositionEndo	0	100	Selects the composition of endoglucanase
CompositionGluco	0	100	Selects the composition of β-glucosidase
halflife	100	200	Defines the number of steps a given enzyme stays active
PrbExo	1	100	Determines the activity of exoglucanase
PrbEndo	1	100	Determines the activity of endoglucanase
PrbGluco	1	100	Determines the activity of β-glucosidase
EnzymeSystem	N/A	N/A	Selects between (i) complexed, (ii) non-complexed, and (iii) hybrid cellulase systems
PrbGluIntake	1	100	Controls the rate of glucose uptake
PrbBioIntake	1	100	Controls the rate of cellobiose uptake
PrbTriIntake	1	100	Controls the rate of cellotriose uptake
BacteriaConcentration	1	100	Determines the number of bacteria in the system
CelluloseChains	1	10	Determines the number of cellulose chains in the system
CelluloseLength	1	20	Selects the length of cellulose chains in the system