(374ab) Functionally-Based, Non-Complexed Cellulase Model Elucidates Product Inhibition Trends in Cellulose Hydrolysis

Cellulase structures clearly suggest that cellulose hydrolysis product inhibition is competitive on the molecular level. Despite this, other kinetic inhibition models, such as non-competitive and uncompetitive, have been suggested to be accurate descriptions of the collective product inhibition effects of cellulase mixtures. Here we present a non-complexed cellulase model that takes into account multiple substrate and enzyme parameters, including competitive inhibition of hydrolysis by glucose and cellobiose. Model results are then validated with literature data. Modeling considerations include both homogeneous and heterogeneous phase enzyme activities and substrate properties such as degree of polymerization (DP) and fraction of beta-glycosidic bonds available to the enzymes for hydrolysis (Fa). This model is shown to be valid for a range of hydrolysis conditions that do not exhibit Michaelis-Menten kinetics or the properties of classic competitive inhibition. Careful consideration of functional interactions at the molecular level is demonstrated to be sufficient to explain a range of observed experimental results at conditions such as high substrate loading, high enzyme loading, and varying substrate type.