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PMID: 21983601 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A mass spectrometry-guided genome mining approach for natural product peptidogenomics.

Nature chemical biology ·Vol. 7 ·No. 11 ·2011-10-09 ·Pages 794-802

Kersten RD, Yang YL, Xu Y, Cimermancic P, Nam SJ, Fenical W, Fischbach MA, Moore BS, Dorrestein PC

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.

MeSH Terms
Amino Acid Sequence Bacterial Proteins/chemistry,genetics,metabolism Biological Products/chemistry,metabolism Gene Expression Regulation, Bacterial/physiology Genomics/methods Genotype Mass Spectrometry/methods Molecular Structure Peptides/chemistry,genetics,metabolism Streptomyces/genetics,metabolism
Chemicals
AmfS protein, Streptomyces griseus Bacterial Proteins Biological Products Peptides
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kersten Roland D
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California, USA.
Yang Yu-Liang
Xu Yuquan
Cimermancic Peter
Nam Sang-Jip
Fenical William
Fischbach Michael A
Moore Bradley S
Dorrestein Pieter C
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Article Info
Journal
Nature chemical biology
Abbr.
Nat Chem Biol
ISSN
1552-4469
DOI
10.1038/nchembio.684
Published
2011-10-09
Epub
2011-00-09
Pages
794-802
Language
English
Region
United States
NLM ID
101231976
PMCID
PMC3258187
Subset
IM
Grants
NCI NIH HHS · R37 CA044848 · United States
NIGMS NIH HHS · R01 GM086283 · United States
NIGMS NIH HHS · R01 GM085770-04 · United States
NCI NIH HHS · R37 CA044848-25 · United States
NIGMS NIH HHS · R01 GM085770 · United States
NIGMS NIH HHS · GM086283 · United States
NIGMS NIH HHS · R01 GM086283-03 · United States
NIGMS NIH HHS · GM085770 · United States
External Links
PubMed source DOI: 10.1038/nchembio.684 PMC Full Text View journal details
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