Integrated omics analysis of the cellulose co-degradation network of Chaetomium thermophilum

Background: Efficient degradation of cellulose is a key bottleneck in the industrialization of biofuels. While fungi achieve substrate conversion through precise regulation of cellulase systems, the systematic mechanisms underlying efficient degradation (encompassing gene transcription, extracellular protein cooperation, and product metabolism) remain unclear in specific fungi, especially thermophilic fungi critical for industrial production. Results: (1) C. thermophilum did not induce cellulases under cellobiose, while microcrystalline cellulose (MCC) strongly activated degradation. CtClr-2 acts as a core transcription factor, directly driving the co-expression of key genes including LPMOs, CDH, and CBH; its deletion reduces MCC degradation efficiency by 30%. (2) Enzyme secretion may follow a three-stage cascade pattern (CBH1-A → LPMOs/CDH-1 → CBH1/2-B), where the selective secretion and temporal synergy of oxidases and hydrolase increase the reducing sugar yield by 60.6%. (3) The sugar acid metabolic network may enable efficient utilization of degradation products and potentially help maintain extracellular pH. Conclusions: This study reveals the efficient "transcriptional regulation-enzyme secretion adaptation" synergistic mechanism in C. thermophilum. CtClr-2 coordinates key genes, and staged enzyme secretion optimizes synergy, while sugar acid metabolism ensures homeostasis. These insights advance thermophilic cellulolysis understanding and provide targets for engineering industrial strains through synthetic biology (for example, enhancing enzyme yield and optimizing degradation efficiency), aiding cost reduction in biofuel production.