Research Progress in the Mechanisms of Microbial Furfural Tolerance and Future Research Prospects for Its Biotechnological Exploitation

Lignocellulose is the most abundant renewable biomass on Earth, and its efficient bioconversion is critical for achieving carbon neutrality, substituting fossil resources, and advancing sustainable biomanufacturing. However, furfural, a dominant inhibitor generated during lignocellulosic pretreatment, severely compromises microbial metabolism and fermentation performance. To date, no systematic review has comprehensively integrated the mechanisms of furfural-induced microbial toxicity with corresponding stress tolerance strategies. This review elaborates on three core themes: the multi-pathway toxic effects of furfural, intrinsic microbial tolerance mechanisms, and advanced strategies for constructing a high-tolerance microbial chassis. Despite considerable progress, several research gaps persist, including poorly understood synergistic or antagonistic interactions between furfural and other hydrolysate inhibitors, insufficient integration of adaptive laboratory evolution, rational design, and random mutagenesis in anti-inhibitor research, and limited understanding of trade-offs between furfural tolerance and industrial fermentation robustness. Future efforts should address these gaps through combinatorial stress simulation, multi-omics profiling, and the “evolve–elucidate–engineer” paradigm, thereby enabling the scalable and stable application of lignocellulosic biomanufacturing.