(254b) Enhancing the Traffic Flow of Enzymes Accelerates the Kinetics of Cellulose Decomposition

Interfacial proteins operate under crowded conditions and exhibit a complex reaction machinery to facilitate biocatalysis. Important modern examples are cellobiohydrolases, which decompose crystalline cellulose microfibrils processively within the plant cell wall and represent key components in second-generation biofuel technologies. To identify rate-limiting mechanisms, we develop a systems-level simulation model of enzyme kinetics with a molecular-scale spatial resolution. The null-event kinetic Monte Carlo and stochastic quasi-static algorithms were used to overcome the stiffness of covering eight orders of magnitude of timescales.  We found cellulose conversion is limited due to slow complexation and excessive jamming of enzyme molecules on the substrate. The ability of involving molecular details in three dimensions allows explicit representation of molecular crowding in propagating enzyme kinetics. The computational results suggest that optimization of complexation and decomplexation between enzyme and substrate is critical for enhancement of cellulose bioconversion rates.