biostudies-literatureKersten RDNCI NIH HHSNIGMS NIH HHS794-802https://www.ebi.ac.uk/biostudies/studies/S-EPMC3258187biostudies-literatureUnknown7(11)Peptide natural products show broad biological properties and are commonly produced by orthogonal ribosomal and nonribosomal pathways in prokaryotes and eukaryotes. To harvest this large and diverse resource of bioactive molecules, we introduce here natural product peptidogenomics (NPP), a new MS-guided genome-mining method that connects the chemotypes of peptide natural products to their biosynthetic gene clusters by iteratively matching de novo tandem MS (MS(n)) structures to genomics-based structures following biosynthetic logic. In this study, we show that NPP enabled the rapid characterization of over ten chemically diverse ribosomal and nonribosomal peptide natural products of previously unidentified composition from Streptomycete bacteria as a proof of concept to begin automating thNature chemical biologyA mass spectrometry-guided genome mining approach for natural product peptidogenomics.PMC3258187GM085770R01 GM085770R37 CA044848R01 GM086283GM086283Fischbach MAFenical WCimermancic PDorrestein PCKersten RDYang YLMoore BSXu YNam SJfalseA mass spectrometry-guided genome mining approach for natural product peptidogenomics.Peptide natural products show broad biological properties and are commonly produced by orthogonal ribosomal and nonribosomal pathways in prokaryotes and eukaryotes. To harvest this large and diverse resource of bioactive molecules, we introduce here natural product peptidogenomics (NPP), a new MS-guided genome-mining method that connects the chemotypes of peptide natural products to their biosynthetic gene clusters by iteratively matching de novo tandem MS (MS(n)) structures to genomics-based structures following biosynthetic logic. In this study, we show that NPP enabled the rapid characterization of over ten chemically diverse ribosomal and nonribosomal peptide natural products of previously unidentified composition from Streptomycete bacteria as a proof of concept to begin automating th2011-01-01T00:00:00Z2011 Oct2026-05-04T07:19:16.479Z2026-04-07T20:14:48.032ZS-EPMC32581872198360110.1038/nchembio.684