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Background  Growing concern about the emergence of antibiotic resistance is compelling the pharmaceutical industry to search for new antimicrobial agents. The availability of genome sequences has enabled the development of computational mining as an important tool in the discovery of natural products with antibiotic effect.    Results  NRPPUR (Non-Ribosomal Peptide and Polyketide Urmite) is a new bioinformatic tool that was created to detect polyketides and non-ribosomal peptide gene clusters (PKS and NRPS) in bacterial genomes using the rpsBlast program. The NRPPUR database was constructed locally by assembling all 3505 available sequences of NRPS-PKS that have been identified by in silico approaches to date, with 164 Biosynthetic Gene Clusters (BGCs) derived from the published literature that have demonstrated antimicrobial activity in vitro. The in silico analysis of 49 intestinal human bacterial genomes using the NRPPUR made it possible to identify 91 BGCs including 89 clusters that had never previously been described. On average, intestinal human bacterial genomes devote nearly 0.8% (±1.4% s.d.) of their genome to NRPS/PKS biosynthesis, with  Bacillus vallismortis ,  Streptomyces massiliensis  and  Bacillus subtilis  genomes apportioning 8.4, 3.6 and 3.15% of their genomes, respectively. When using the cross-streak method,  S. massiliensis  displayed antibacterial activity against many Gram-positive and negative bacteria including methicillin-resistant  Staphylococcus aureus  (MRSA).    Conclusions  NRPPUR has proven to be a very useful tool for the primary in silico selection of species with potential antimicrobial activity and human microbiota could be the future source of new antimicrobial discoveries. Further exploration of this and other ecological niches, coupled with high-throughput antibacterial activity screening should be envisaged.    Electronic supplementary material  The online version of this article (10.1186/s12859-018-2479-5) contains supplementary material, which is available to authorized users.

Full-length title: NRPPUR database search and in vitro analysis identify an NRPS-PKS biosynthetic gene cluster with a potential antibiotic effect