Utilization of lignocellulosic biomass as sustainable feedstock for the bioproduction of n-butanol as an advanced biofuel: current progress and future perspectives

Abstract

n-Butanol is a promising advanced biofuel and versatile platform chemical. However, its fermentative production by solventogenic clostridial strains remains economically limited by reliance on costly edible feedstocks of corn and sugarcane. Lignocellulosic biomass provides an abundant, non-food alternative, but its effective conversion necessitates pretreatment which inevitably generates weak acids, furan derivatives, and lignin-derived phenolic compounds. These by-products synergistically inhibit clostridial metabolism by disrupting pH balance, depleting NADH/NADPH, and compromising membrane integrity. To address this bottleneck, this review systematically examines the formation and inhibitory effects of these compounds, and then summarizes the recent strategies of metabolic engineering and co-culture for enhancing the tolerance of strains against various pretreatment-derived inhibitors. In addition, the review traces the progress of pretreatment technologies from conventional acid, alkaline, and physicochemical methods to emerging ionic liquids and deep eutectic solvents, and compares their influence on butanol fermentation performance. By linking lignocellulose pretreatment, inhibition mechanisms, metabolic engineering, and bioprocess engineering, this review provides a systems-level framework for designing more efficient lignocellulosic butanol pathways. Future research interests are also provided, including predictive modeling to control inhibitor generation, strain improvement for lignin-derived phenolic tolerance, techno-economic analysis and life-cycle assessment, and integrated lignin valorization, all aimed at advancing economically viable and sustainable biorefinery processes.