*4.7. Figures Design*

Figures were designed using D3 (or D3.js, a JavaScript library for visualizing data using web standards) [114], R software (R Development Core Team, 2019) [115], and Adobe Illustrator.

#### **5. Conclusions**

Our findings show that there is a considerable novelty to be found through exploring the genomes of host-associated microbes from animals in remote ecologies for biosynthetic pathways with the potential to shape host-associated microbial population structures. The novel compounds and natural bacteriocin variants discovered provide first leads for the derivation of new approaches for managing human-microbe interactions in health and disease.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/10 .3390/md19060328/s1, Table S1: Sequencing statistics, genome sizes, fold coverage, G+C content, of the *Enterococcus* spp. sequenced. Table S2: Reference genomes used to confirm the enterococci species. Table S3: Putative antimicrobial compounds biosynthesis gene clusters (BGCs) data predicted with antiSMASH5 and Bagel4 software. Table S4: Class I, class II, and class III unknown bacteriocins BGCs data that were not previously identified in antiSMASH5 and Bagel4 databases. Table S5: Class II and class III bacteriocin sequences predicted with antiSMASH5 and Bagel4 software. Table S6: Reference sequences from Bagel4 and Uniprot databases. Figure S1: The alignment of putative enterolysin A (class III) sequences (first branch) from *E. hirae* genomes using Clustal Omega software. Figure S2: The alignment of putative enterolysin A (class III) sequences (second branch) from *E. hirae* genomes using Clustal Omega software. Figure S3: The alignment of putative enterolysin A (class III) sequences (third branch) from *E. faecalis* genomes using Clustal Omega software. Figure S4: The alignment of four different enterolysin A (class III) and three different references (Bagel 62.3: *E. faecalis* LMG 2333; Bagel 63.3: *E. faecalis*; and Bagel 64.3: *Lactobacillus acidophilus*) using Clustal Omega software. Figure S5: The alignment of putative propionicin SM1 (class III) and reference sequence using Clustal Omega software. Figure S6: The alignment of putative Class IIa bacteriocins and reference sequences using Clustal Omega software. Figure S7: The alignment of putative class IIb bacteriocins and reference sequences using Clustal Omega software. Figure S8: The alignment of putative class II circular bacteriocin carnocyclin A and reference sequence using Clustal Omega software. Figure S9: The alignment of putative class II leaderless bacteriocin enterocin EJ97 and reference sequence using Clustal Omega software. Figure S10: The alignment of putative class II other bacteriocins and reference sequences using Clustal Omega software.

**Author Contributions:** J.P., A.S., M.P.-B. and M.S.G. designed the study. Samples were collected by M.T. The bacteria isolation, extraction, and genome sequencing were performed by J.P. and T.G.S.P. Bioinformatics approaches, analyze of data, and figures were designed by J.P., M.P.-B., R.C.Z.L., Í.M.S.C. and R.L.-B. The original draft manuscript was written by J.P., M.P.-B., A.S. and M.S.G. This study was funded and/or supervised by A.S., J.F., P.A.d., A.P.G.F. and M.S.G. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the NIH grant AI083214—*Harvard-wide program on antibiotic resistance*–, Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil, and Coordenação e Aperfeiçoamento de Pessoal de Nível Superior (CAPES) of the Brazilian government (CNPq; 40788/2018-4).

**Data Availability Statement:** The novel genome sequences were deposited at DDBJ/ENA/GenBank as whole-genome shotgun projects under the accession numbers according to Table S1.

**Acknowledgments:** The authors would like to thank the Center for Coastal Studies, Limnology and Marine (CECLIMAR) for assistance in collecting samples and to members of the *Enteromar* Research Group for critical feedback on the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

