Understanding the toxicity of lignin-derived phenolics towards enzymatic saccharification of lignocellulose for rationally developing effective in-situ mitigation strategies to maximize sugar production from lignocellulosic biorefinery

[Display omitted] •The pretreatment-severity-dependent inhibition is mainly due to phenolics.•A QSAR model was built to describe the phenolics caused inhibition.•Electrophilicity and hydrophobicity of phenolics determine the inhibition potential.•Phenolics bind to cellulases by hydrophobic interactions, hydrogen/covalent bonds.•The inhibition of cellulose hydrolysis by phenolics was greatly alleviated in-situ. The lignin-derived phenolics are highly inhibitory toward lignocellulose enzymatic hydrolysis, while the relationship between phenolic structure and inhibitory effect is still not fully understood. In this study, the compositions of phenolics from dilute acid pretreated wheat straw were analyzed and their impact on cellulose hydrolysis was studied. With increase of pretreatment severity, more toxic phenolics were produced from lignin degradation reactions, which were the major contributor to the increased inhibitory effect of pretreatment hydrolysate towards cellulases. Through analyzing the relationship of phenolic structure and their inhibitory effect, a useful model was developed to predict the phenolics-caused inhibition by combining the indexes of electrophilicity and hydrophobicity. Further, through understanding the interactions between phenolics and cellulases, a novel biocomponent alleviator was rationally designed to block the phenolics-cellulase interactions, the degree of improvement of enzymatic hydrolysis reached as high as 135.8%. This study provides directions for developing more effective pretreatment and detoxification methods.