Host-adapted enzymatic deconstruction of acetylated xylan limits immune activation and facilitates mutualistic colonization of monocot roots

Intracellular accommodation of beneficial fungi requires host cell wall remodeling that avoids excessive immune activation. The root endophyte Serendipita indica, a generalist mutualist capable of colonizing both monocot and dicot plants, employs a monocot-specific enzymatic module to deconstruct acetyl-xylan, the dominant hemicellulose of grasses. Central to this module are the glycoside hydrolase SiGH11, which releases acetylated xylooligosaccharides, and SiAXE, a previously uncharacterized SGNH-like acetyl-xylan esterase that sequentially removes acetyl groups from soluble XOS. Both enzymes are co-expressed within a monocot-enriched transcriptional program that also includes sugar transporters and metabolic regulators. Their coordinated activity, together with co-expressed exo-enzymes, promotes efficient xylan hydrolysis while limiting the prolonged accumulation of immunogenic damage-associated molecular patterns (DAMPs). Functional genetics demonstrated that SiAXE is required for sustained intracellular growth in monocot roots: its deletion impaired colonization, whereas overexpression transiently accelerated entry but provoked immune responses, underscoring the importance of temporal regulation and enzyme coordination for immune-compatible colonization. These findings provide mechanistic insight into an immune-compatible fungal strategy for host cell wall remodeling and reveal how a broadly colonizing mutualist has repurposed ancestral saprotrophic enzymes into specialized host-adapted modules that balance nutrient acquisition with immune modulation.