title: A mass spectrometry-guided genome mining approach for natural product peptidogenomics.
abstract: 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 the genome-mining process. We show the identification of lantipeptides, lasso peptides, linardins, formylated peptides and lipopeptides, many of which are from well-characterized model Streptomycetes, highlighting the power of NPP in the discovery of new peptide natural products from even intensely studied organisms.
authors: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California, USA.
authors: Roland D
authors: RD
authors: Kersten
authors: Yu-Liang
authors: YL
authors: Yang
authors: Yuquan
authors: Y
authors: Xu
authors: Peter
authors: P
authors: Cimermancic
authors: Sang-Jip
authors: SJ
authors: Nam
authors: William
authors: W
authors: Fenical
authors: Michael A
authors: MA
authors: Fischbach
authors: Bradley S
authors: BS
authors: Moore
authors: Pieter C
authors: PC
authors: Dorrestein
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D023281:Genomics / Q000379:methods*; D005838:Genotype; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism
chemical_list: C450432:AmfS protein, Streptomyces griseus; D001426:Bacterial Proteins; D001688:Biological Products; D010455:Peptides