Non-covalent interactions between lignin and cellulase: From molecular mechanisms to precision regulation.

Lignocellulosic biomass is the most abundant renewable carbon source; its efficient utilization helps reduce dependence on fossil raw materials and promotes sustainable economic and social development. However, the sugar platform technology based on enzymatic hydrolysis and conversion of lignocellulose still faces major challenges. Among them, the non-productive adsorption of cellulase by lignin seriously restricts the efficiency and economics of the enzymatic hydrolysis process. Studies have shown that the presence of lignin can reduce cellulase hydrolysis efficiency by 30 %-80 %, and enzyme loading must be increased by 2-5 fold to achieve the same saccharification yield, significantly raising production costs. How to overcome the recalcitrance of lignin to enzymatic hydrolysis is an important topic in the industrial utilization of lignocellulosic biomass. Non-productive adsorption mainly relies on short-range non-covalent interactions such as hydrophobic interactions, hydrogen bonding, and electrostatic interactions. These interactions directly promote the ineffective binding of enzymes to the lignin surface. Recent studies have further revealed that long-range Van der Waals forces, electric double-layer interactions, and long-range hydrophobic interactions play an important promoting role in the initial approach stage between enzymes and lignin. Together, they constitute a long-range capture - short-range locking multi-step adsorption model, further exacerbating the intensity and persistence of non-productive adsorption. This review systematically elucidates the types and mechanisms of lignin-cellulase non-covalent interactions, analyzes the impacts of lignin structural characteristics (unit composition, functional groups, molecular weight) and cellulase properties (domain functions, surface hydrophobicity/charge), and evaluates current mitigation strategies.