Physiological response of solventogenic clostridia to lignocellulose-derived inhibitors

Lignocellulose represents a sustainable feedstock for the production of platform chemicals, yet its potential is influenced by inhibitory compounds that impair microbial performance. Among microbial producers, solventogenic Clostridium species are particularly promising for bio-based solvent production, notably butanol, but their physiology and productivity are highly sensitive to lignocellulose-derived inhibitors. This review comprehensively summarizes how these inhibitors affect growth, viability, sporulation, membrane integrity, efflux, stress responses, and metabolic pathways, including central metabolism, redox balance, and detoxification, specifically in solventogenic Clostridium species, predominantly Clostridium acetobutylicum, Clostridium beijerinckii, Clostridium saccharobutylicum and Clostridium saccharoperbutylacetonicum. Available studies indicate that cellular responses are complex and depend on both strain and experimental conditions. Knowledge gaps persist regarding the stimulatory effects of certain inhibitors at low concentrations and detoxification pathways involved. To expand information about inhibitor transformation, Clostridium tyrobutyricum, a closely related species, is also included. In addition, strategies for mitigating the negative effects of inhibitors, extending beyond genetic engineering approaches, are discussed. By summarizing the available data, this review aims to support the utilization of solventogenic clostridia as promising producers of solvents and to contribute to their integration into lignocellulose-based industrial biotechnological processes.