Metabolic and molecular modelling of zebrafish gut biome to unravel antimicrobial peptides through metagenomics

Recently efforts have been taken for unravelling mysteries between host-microbe interactions in gut microbiome studies of model organisms through metagenomics. Co-existence and the co-evolution of the microorganisms is the significant cause of the growing antimicrobial menace. There needs a novel approach to develop potential antimicrobials with capabilities to act directly on the resistant microbes with reduced side effects. One such is to tap them from the natural resources, preferably the gut of the most closely related animal model. In this study, we employed metagenomics approaches to identify the large taxonomic genomes of the zebra fish gut. About 256 antimicrobial peptides were identified using gene ontology predictions from Macrel and Pubseed servers. Upon the property predictions, the top 10 antimicrobial peptides were screened based on their action against many resistant bacterial species, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, E. coli, and Bacillus cereus. Metabolic modelling and flux balance analysis (FBA) were computed to conclude the antibiotic such as tetracycline, cephalosporins, puromycin, neomycin biosynthesis pathways were adopted by the microbiome as protection strategies. Molecular modelling strategies, including molecular docking and dynamics, were performed to estimate the antimicrobial peptides' binding against the target-putative nucleic acid binding lipoprotein and confirm stable binding. One specific antimicrobial peptide with the sequence “MPPYLHEIQPHTASNCQTELVIKL” showed promising results with 53% hydrophobic residues and a net charge +2.5, significant for the development of antimicrobial peptides. The said peptide also showed promising interactions with the target protein and expressed stable binding with docking energy of −429.34 kcal/mol and the average root mean square deviation of 1 A0. The study is a novel approach focusing on tapping out potential antimicrobial peptides to be developed against most resistant bacterial species. [Display omitted] •The study was focused to unravelled the mysteries of Zebrafish gut biome through metagenomics.•Demonstrated the significant biosynthetic and degradation pathways adapted by the zebra fish.•Antimicrobial peptides were predicted with activity against many resistant bacteria.•Proved the antimicrobial activity of the peptide and its dynamics against the target.