Multi-omics analysis reveals protein kinase A-associated regulatory remodeling during adaptation of Trichoderma reesei to lignocellulosic substrate

The filamentous fungus Trichoderma reesei is a major industrial source of holocellulolytic enzymes, and its response to complex carbon sources is regulated by nutrient-sensing pathways, including cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling. Here, we used transcriptomics, quantitative proteomics, and phosphoproteomics to analyze PKAc1-associated responses in the parental strain QM9414 and a Δ pkac1 strain cultivated under glucose or sugarcane bagasse conditions. Deletion of pkac1 was associated with altered growth-related phenotypes and reduced extracellular activities of selected biomass-depolymerizing enzymes. Multi-omics profiling revealed condition-dependent changes affecting subsets of carbohydrate-active enzymes (CAZymes) genes and proteins, nutrient transporters, stress-associated proteins, and regulatory factors. Phosphoproteomics identified phosphorylation-state changes associated with pkac1 deletion, including reduced phosphorylation at sites enriched for the PKA consensus motif. In silico peptide docking was used to identify candidate PKAc1 substrates for future validation, including a Sec7-derived peptide with favorable docking behavior relative to the control peptide. Together, these data support a working model in which PKAc1 contributes to regulatory and phosphorylation-state remodeling during adaptation to sugarcane bagasse, with effects on the magnitude and/or timing of selected CAZyme-related outputs in T. reesei .