Phylogenetic Insights into Enzybiotic with Novel Properties

The evolution of enzymes is crucial for the development of novel therapeutic agents against multidrug-resistant bacteria. This study explored a diverse set of enzymes, including amidases, lysozymes, and proteases, with known antimicrobial properties, sourced from uncultured bacterial strains and species, such as Enterococcus faecium and Lysobacter capsici. Using Clustal Omega for multiple sequence alignment, we constructed a high-resolution phylogenetic tree to investigate evolutionary relationships and functional diversity within this enzyme cohort. Phylogenetic analysis revealed distinct clustering patterns among the enzyme families. M۲۳ metallopeptidase enzymes from Lysobacter capsici showed strong conservation of catalytic residues and tight clustering, suggesting an evolutionary pressure to preserve their peptidoglycan-degrading activity. In contrast, amidases exhibited significant divergence, especially those from uncultured bacteria, implying adaptive modifications in their active sites to target structurally diverse bacterial cell walls. Proteases are split into two major clades, reflecting variations in substrate specificity and structural domains. Enzymes from uncultured bacterial strains formed unique clades that were distinct from known sequences, suggesting previously uncharacterized antimicrobial mechanisms. Notably, enzymes, such as N-acetylmuramoyl-L-alanine amidase, were identified as phylogenetic outliers, indicating potential evolutionary transitions that may broaden their activity spectrum. These findings underscore the potential of uncultured microbiota as reservoirs of novel enzymatic functions. By integrating phylogenetic analysis with functional predictions, we have provided a comprehensive understanding of the structural and functional evolution of antimicrobial enzymes. Our study offers a valuable framework for discovering and optimizing bioactive enzymes, with future research incorporating structural bioinformatics and functional assays to explore their mechanistic roles in combating antimicrobial resistance.

کلیدواژه ها:

antimicrobial enzymes ، phylogenetic analysis ، enzyme evolution ، uncultured bacteria ، Bioinformatics