Advancing cellulose degradation through synthetic biology: engineered pathways and microbial systems for sustainable...

Fiber, the most abundant organic polymer in nature, is widely recognized as a foundational sustainable material with diverse applications across industrial, medical, and consumer domains. Owing to its renewability and widespread availability, it also serves as a critical alternative energy source in agriculture, enabling more sustainable livestock production through the efficient conversion of fibrous feedstuffs, thereby supporting the principles of a circular bioeconomy. Cellulose, which constitutes up to 80% of plant fiber, contains tightly packed crystalline regions that confer strong resistance to microbial degradation. Other key obstacles to efficient cellulose digestion in the gut include the absence of critical cellulolytic genes, low enzymatic activity, a lack of natural activators, and the presence of cellulase inhibitors. Synthetic biology provides innovative molecular-level strategies to overcome key technical barriers in cellulose degradation. These approaches employ targeted modifications at nucleic acid and protein levels, including the introduction of engineered genes, synthetic regulators, and optimized enzymes, to develop high-performance microbial systems with enhanced cellulose-degrading capabilities. Furthermore, genetic modifications like the knockout of inhibitory genes and knock-in of activator genes, combined with rational redesign of multi-enzyme complexes, can significantly improve the secretion and catalytic efficiency of cellulases. When integrated with artificial intelligence, synthetic biology enables predictive screening and precision engineering of microbial strains for highly efficient cellulose degradation. This review comprehensively summarizes recent advances in synthetic biology approaches for improving cellulose degradation and highlights how these tools can optimize fiber utilization in sustainable agricultural and industrial applications.