Constructing cellulosomes to enhance lignocellulose degradation and biotechnological applications: A review

The increasing demand for sustainable and renewable energy sources has intensified research efforts on the development of efficient lignocellulose bioprocessing strategies. Cellulosomes are sophisticated multi-enzyme complexes evolved in anaerobic microbes to efficiently degrade lignocellulosic biomass. This review highlights recent advances in both native and engineered cellulosome systems, emphasizing their structural diversity, synergistic mechanisms, and industrial relevance. Comparative analyses of native cellulosomes, including those from Clostridium sp., Ruminococcus sp, and Bacteroides sp., reveals the evolutionary features in scaffoldin architecture, cohesin-dockerin specificity, and substrate targeting. Building on these natural frameworks, 'Designer cellulosomes' have emerged as modular platforms for enhancing catalytic synergy, thermostability and ultimately the consolidated bioprocessing (CBP). Advances in synthetic scaffoldin design, microbial host optimization (e.g., Saccharomyces cerevisiae, Bacillus subtilis and Kluyveromyces marxianus) and operon engineering have enabled tailored enzyme integration in the cellulosome complex and improved biomass degradation. The incorporation of hemicellulases, ligninases and oxidative enzymes into the cellulosome complex further enhances saccharification efficiency and overcomes biomass recalcitrance. Emerging concepts such as double-dockerin modules, tripartite dockerin interactions and glycosylation-enhanced stability redefine cellulosome functionality and offer new design principles for synthetic biology. Additionally, the discovery of human gut-associated cellulosomes suggests broader ecological and therapeutic applications. This review highlights designer cellulosomes as promising next-generation biocatalysts for sustainable biofuel and biochemical production.