Sensitivity analysis identifies the factors driving the enzymatic saccharification of lignocellulose

Corn stover is the most abundant form of crop residue that can serve as a source of lignocellulosic biomass in biorefinery approaches, for instance for the production of bioethanol. In such biorefinery processes, the constituent polysaccharide biopolymers are typically broken down into simple monomeric sugars by enzymatic saccharification, for further downstream fermentation into bioethanol. However, the recalcitrance of this material to enzymatic saccharification invokes the need for innovative pre-treatment methods to increase sugar conversion yield. Here, we focus on experimental glucose conversion time-courses for corn stover lignocellulose that has been pre-treated with different acid-catalysed processes and intensities. We identify the key parameters that determine enzymatic saccharification dynamics by performing a Sobols sensitivity analysis on the comparison between the simulation results from our complex stochastic biophysical model, and the experimental data that we accurately reproduce. We find that the parameters relating to cellulose crystallinity and those associated with the cellobiohydrolase activity are predominantly driving the enzymatic saccharification dynamics. We confirm our computational results using mathematical calculations for a purely cellulosic substrate. On the one hand, having identified that only five parameters drastically influence the saccharification dynamics allows us to reduce the dimensionality of the parameter space (from nineteen to five parameters), which we expect will significantly speed up our fitting algorithm for comparison of experimental and simulated saccharification time-courses. On the other hand, these parameters directly highlight key targets for experimental endeavours in the optimisation of pre-treatment and saccharification conditions. Finally, this systematic and two-fold theoretical study, based on both mathematical and computational approaches, provides experimentalists with key insights that will support them in rationalising their complex experimental results. O_TEXTBOXSIGNIFICANCE The recalcitrance of lignocellulosic biomass to enzymatic saccharification processes necessitates innovative biorefinery pre-treatment processes with the goal of increasing glucose conversion yields. We implement a systematic Sobols sensitivity analysis on the comparison between the simulation results from our complex stochastic biophysical model, and experimental glucose conversion time-courses data for pre-treated corn stover lignocellulose that we accurately reproduce with our model. Our results, reinforced with analytical calculations, highlight the key parameters which govern the dynamics of enzymatic saccharification of lignocellulose. Thus, this study does not only drastically reduce the model parameter space from nineteen free parameters to only five key ones, but it also provides valuable insights that can guide future experiment design efforts, and the rationalisation of complex experimental datasets. C_TEXTBOX