*Article* **Genome Mining for Antimicrobial Compounds in Wild Marine Animals-Associated Enterococci**

**Janira Prichula 1, Muriel Primon-Barros 1, Romeu C. Z. Luz 1, Ícaro M. S. Castro 1, Thiago G. S. Paim 1, Maurício Tavares 2, Rodrigo Ligabue-Braun 3, Pedro A. d'Azevedo 1, Jeverson Frazzon 4, Ana P. G. Frazzon 5, Adriana Seixas <sup>3</sup> and Michael S. Gilmore 6,7,\***


**Abstract:** New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, we identified and characterized biosynthetic gene clusters encoding antimicrobial compounds in host-associated enterococci recovered from fecal samples of wild marine animals remote from human-affected ecosystems. Putative biosynthetic gene clusters in the genomes of 22 *Enterococcus* strains of marine origin were predicted using antiSMASH5 and Bagel4 bioinformatic software. At least one gene cluster encoding a putative bioactive compound precursor was identified in each genome. Collectively, 73 putative antimicrobial compounds were identified, including 61 bacteriocins (83.56%), 10 terpenes (13.70%), and 2 (2.74%) related to putative nonribosomal peptides (NRPs). Two of the species studied, *Enterococcus avium* and *Enterococcus mundtti*, are rare causes of human disease and were found to lack any known pathogenic determinants but yet possessed bacteriocin biosynthetic genes, suggesting possible additional utility as probiotics. Wild marine animal-associated enterococci from human-remote ecosystems provide a potentially rich source for new antimicrobial compounds of therapeutic and industrial value and potential probiotic application.

**Keywords:** enterococci; genome-wide analysis; bacteriocins; probiotics; wild marine species
