Designing novel cellulase systems through agent-based modeling and global sensitivity analysis.
Experimental techniques allow engineering of biological systems to modify functionality; however, there still remains a need to develop tools to prioritize targets for modification. In this study, agent-based modeling (ABM) was used to build stochastic models of complexed and non-complexed cellulose hydrolysis, including enzymatic mechanisms for endoglucanase, exoglucanase, and β-glucosidase activity. Modeling results were consistent with experimental observations of higher efficiency in complexed systems than non-complexed systems and established relationships between specific cellulolytic mechanisms and overall efficiency. Global sensitivity analysis (GSA) of model results identified key parameters for improving overall cellulose hydrolysis efficiency including: (1) the cellulase half-life, (2) the exoglucanase activity, and (3) the cellulase composition. Overall, the following parameters were found to significantly influence cellulose consumption in a consolidated bioprocess (CBP): (1) the glucose uptake rate of the culture, (2) the bacterial cell concentration, and (3) the nature of the cellulase enzyme system (complexed or non-complexed). Broadly, these results demonstrate the utility of combining modeling and sensitivity analysis to identify key parameters and/or targets for experimental improvement.
Department of Biological Systems Engineering; Virginia Tech; Blacksburg, VA USA.
Advait A
AA
Apte
Department of Biological Systems Engineering; Virginia Tech; Blacksburg, VA USA.
Ryan S
RS
Senger
Department of Chemical and Life Science Engineering; Virginia Commonwealth University; Richmond, VA USA.
Stephen S
SS
Fong
D002480:Cellulase / Q000737:chemistry*; D040143:Cellulomonas / Q000201:enzymology; D002482:Cellulose / Q000737:chemistry*; D046973:Ruminiclostridium cellulolyticum / Q000201:enzymology; D048013:Acetivibrio thermocellus / Q000201:enzymology; D045848:Fibrobacter / Q000201:enzymology; D006026:Glycoside Hydrolases / Q000737:chemistry; D006868:Hydrolysis; D008958:Models, Molecular; D015202:Protein Engineering; D012680:Sensitivity and Specificity
D002482:Cellulose; D006026:Glycoside Hydrolases; D002480:Cellulase
agent based modeling; cellulose degradation strategies; cellulose hydrolysis; enzyme engineering; global sensitivity analysis; metabolic engineering