Mechanistic kinetic models of enzymatic cellulose hydrolysis—A review

• Published in: Biotechnology and bioengineering 2017-07, Vol.114 (7), p.1369-1385
• Main Authors: Jeoh, Tina, Cardona, Maria J., Karuna, Nardrapee, Mudinoor, Akshata R., Nill, Jennifer
• Format: Article
• Language: English
• Subjects: Binding Sites; Bioconversion; Biofuels; Catalysis; Cellulase; cellulases; Cellulases - chemistry; Cellulases - ultrastructure; cellulase‐cellulose interactions; Cellulolytic enzymes; Cellulose; Cellulose - chemistry; cellulose hydrolysis mechanism; cellulose structure; Complexation; complexation and decomplexation; Computer Simulation; Enzyme Activation; Enzymes; Hydrolysis; Kinetics; Lignocellulose; Limiting factors; Modelling; Models, Chemical; Models, Molecular; Polymerization; Protein Binding; rate‐limiting cellulose property; Reviews; Structure-Activity Relationship
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.26277

ABSTRACT Bioconversion of lignocellulose forms the basis for renewable, advanced biofuels, and bioproducts. Mechanisms of hydrolysis of cellulose by cellulases have been actively studied for nearly 70 years with significant gains in understanding of the cellulolytic enzymes. Yet, a full mechanistic understanding of the hydrolysis reaction has been elusive. We present a review to highlight new insights gained since the most recent comprehensive review of cellulose hydrolysis kinetic models by Bansal et al. (2009) Biotechnol Adv 27:833–848. Recent models have taken a two‐pronged approach to tackle the challenge of modeling the complex heterogeneous reaction—an enzyme‐centric modeling approach centered on the molecularity of the cellulase‐cellulose interactions to examine rate limiting elementary steps and a substrate‐centric modeling approach aimed at capturing the limiting property of the insoluble cellulose substrate. Collectively, modeling results suggest that at the molecular‐scale, how rapidly cellulases can bind productively (complexation) and release from cellulose (decomplexation) is limiting, while the overall hydrolysis rate is largely insensitive to the catalytic rate constant. The surface area of the insoluble substrate and the degrees of polymerization of the cellulose molecules in the reaction both limit initial hydrolysis rates only. Neither enzyme‐centric models nor substrate‐centric models can consistently capture hydrolysis time course at extended reaction times. Thus, questions of the true reaction limiting factors at extended reaction times and the role of complexation and decomplexation in rate limitation remain unresolved. Biotechnol. Bioeng. 2017;114: 1369–1385. © 2017 Wiley Periodicals, Inc. Mechanistic kinetic models of cellulose hydrolysis since 2009 either capture rate‐limiting cellulase‐cellulose interaction steps (enzyme‐centric) or focus on modeling the contributions of the insoluble cellulose substrate to cellulose hydrolysis kinetics (substrate‐centric). Complexation/decomplexation processes have been shown to be rate‐limiting at the molecular level while the surface area and degrees of polymerization of insoluble cellulose limit initial hydrolysis rates. Despite these advances, the question of why cellulose hydrolysis rates decline rapidly at extended reaction times has yet to be answered.