Abstract
White-rot fungi play a crucial role in terrestrial carbon cycling by decomposing lignocellulose, particularly lignin, in plant cell walls. The degradation process is initiated by the fungal perception of lignocellulosic signals, which trigger a complex regulatory network controlling lignocellulolytic enzyme expression. However, the ecological and molecular mechanisms underlying how these fungi sense lignocellulosic signals and regulate their degradation capacity remain unclear. In this study, a degenerated Trametes hirsuta AH28-2 that lost lignocellulolytic degradation capacity was generated through successive subcultures. Phenotypic stability, transcriptomic analyses, and functional validation revealed that ThIPK1, a key gene in the inositol polyphosphate pathway, regulates the orchestrated expression of lignocellulolytic enzymes in response to distinct lignin monomers. Epigenetic modifications, particularly 5mC methylation, were identified as mediators of signal transduction and regulation for ThIPK1 and its downstream Zn2Cys6 transcription factors, which differentially control lignocellulolytic gene transcription. IPK1 exhibits a closer relationship among white-rot fungi compared to their phylogenetic relationships. These findings provide novel insights into the molecular basis of white-rot fungal adaptation to lignocellulosic environments, contributing to our understanding of microbial-driven lignin turnover in forest ecosystems.IMPORTANCEWhite-rot fungi are among the most efficient lignocellulose degraders in nature. Understanding how white-rot fungi sense and respond to lignocellulose is critical for deciphering microbial contributions to forest carbon turnover. Despite their ecological importance, the molecular mechanisms underlying lignin signal perception remain elusive. In this study, we uncover a regulatory axis involving inositol polyphosphate signaling and epigenetic modulation that connects environmental lignin cues to the transcriptional control of lignocellulolytic enzymes. By identifying ThIPK1 as a crucial regulator and revealing 5mC methylation and Zn2Cys6 transcription factors as downstream effectors, we demonstrate how fungi integrate chemical signals from lignin monomers into adaptive gene expression. These findings not only reveal a novel lignin-responsive regulatory mechanism but also provide a framework for understanding fungal adaptation and function in dynamic, lignin-rich environments.