Comparative Genomic and Functional Profiling of ECM-Targeting Enzymes in

Purpose: The human extracellular matrix (ECM) provides essential cues for intestinal homeostasis. While most studies focus on ECM degradation by host cells, our prior work suggests that commensal gut microbes may also contribute to these remodeling processes. Here, we continue exploring this novel dimension of host-microbe interactions by profiling the proteolytic diversity and substrate-specific activity of ECM-targeting enzymes across species of Methods: We curated a custom ECM-specific enzyme database from the BRENDA repository and used it to perform comparative genomic analyses across 11 Results: ECM-targeting CAZymes and proteases were broadly encoded across all 11 genomes, with gene counts positively correlated with genome size and GAG-associated genes comprising the largest substrate category. Experimental degradation assays revealed species- and substrate-specific activity patterns, including elastin degradation restricted to a subset of species, a capacity previously undocumented in intestinal Conclusions: Our findings position commensal