MiGPC: a comprehensive catalog of enzybiotics from environmental metagenomes

Antimicrobial agents play a vital role in human and environmental health, with applications spanning medicine, food preservation, agriculture, and biotechnology. Among them, enzybiotics enzyme-based antimicrobials have emerged as powerful alternatives to conventional antibiotics due to their targeted mechanisms and lower propensity for resistance. Beyond their medical relevance, enzybiotics have emerging applications in food preservation, animal health, and agriculture, thereby broadening their industrial and environmental value. To support the discovery and characterization of these versatile biomolecules, we present the first genome-resolved metagenomic gene and protein targeted enzybiotic catalog focused on enzybiotics, derived from diverse environmental microbiomes. The Microbial Enzybiotic Gene and Protein Catalog (MiGPC), integrates 15 whole-metagenome datasets from oceans, soils, fecal samples, vegetation, and plastic-contaminated environments, capturing a wide ecological spectrum. Enzybiotic sequences were compiled through a hybrid strategy combining public database mining and manual literature curation, yielding over 136,000 enzybiotic sequences, 7654 metagenome-assembled genomes (MAGs), and ~ 100 million unique genes and proteins. MiGPC integrates taxonomic and enzybiotic gene profiles, offering a robust platform for the discovery, annotation, and ecological mapping of antimicrobial enzymes. Functional analyses using KEGG and eggNOG revealed that approximately 62% of the genes remained uncharacterized, highlighting a rich source of potentially novel functions. Glycoside hydrolases and glycosyl transferases were the most prevalent CAZyme families, while the dominant enzybiotic-producing taxa belonged primarily to the Pseudomonadota and Bacillota phyla. Statistical modeling uncovered two major ecological clusters that distinguished polluted from relatively pristine environments. MiGPC enables high-throughput screening of previously unexplored metagenomes, facilitating the identification of novel antimicrobial agents from under characterized ecosystems. Overall, MiGPC represents a landmark resource that will support multi-omics research, microbial ecology, and the development of next-generation biotechnological solutions based on enzybiotics.