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Title: Automated genome mining of ribosomal peptide natural products

Abstract

Ribosomally synthesized and posttranslationally modified peptides (RiPPs), especially from microbial sources, are a large group of bioactive natural products that are a promising source of new (bio)chemistry and bioactivity (1). In light of exponentially increasing microbial genome databases and improved mass spectrometry (MS)-based metabolomic platforms, there is a need for computational tools that connect natural product genotypes predicted from microbial genome sequences with their corresponding chemotypes from metabolomic datasets. Here, we introduce RiPPquest, a tandem mass spectrometry database search tool for identification of microbial RiPPs and apply it for lanthipeptide discovery. RiPPquest uses genomics to limit search space to the vicinity of RiPP biosynthetic genes and proteomics to analyze extensive peptide modifications and compute p-values of peptide-spectrum matches (PSMs). We highlight RiPPquest by connection of multiple RiPPs from extracts of Streptomyces to their gene clusters and by the discovery of a new class III lanthipeptide, informatipeptin, from Streptomyces viridochromogenes DSM 40736 as the first natural product to be identified in an automated fashion by genome mining. The presented tool is available at cy-clo.ucsd.edu.

Authors:
; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1171294
Report Number(s):
PNNL-SA-99212
44679; KP1704020
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
ACS Chemical Biology, 9(7):1545-1551
Additional Journal Information:
Journal Name: ACS Chemical Biology, 9(7):1545-1551
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

Citation Formats

Mohimani, Hosein, Kersten, Roland, Liu, Wei, Wang, Mingxun, Purvine, Samuel O., Wu, Si, Brewer, Heather M., Pasa-Tolic, Ljiljana, Bandeira, Nuno, Moore, Bradley S., Pevzner, Pavel A., and Dorrestein, Pieter C. Automated genome mining of ribosomal peptide natural products. United States: N. p., 2014. Web. doi:10.1021/cb500199h.
Mohimani, Hosein, Kersten, Roland, Liu, Wei, Wang, Mingxun, Purvine, Samuel O., Wu, Si, Brewer, Heather M., Pasa-Tolic, Ljiljana, Bandeira, Nuno, Moore, Bradley S., Pevzner, Pavel A., & Dorrestein, Pieter C. Automated genome mining of ribosomal peptide natural products. United States. https://doi.org/10.1021/cb500199h
Mohimani, Hosein, Kersten, Roland, Liu, Wei, Wang, Mingxun, Purvine, Samuel O., Wu, Si, Brewer, Heather M., Pasa-Tolic, Ljiljana, Bandeira, Nuno, Moore, Bradley S., Pevzner, Pavel A., and Dorrestein, Pieter C. Thu . "Automated genome mining of ribosomal peptide natural products". United States. https://doi.org/10.1021/cb500199h.
@article{osti_1171294,
title = {Automated genome mining of ribosomal peptide natural products},
author = {Mohimani, Hosein and Kersten, Roland and Liu, Wei and Wang, Mingxun and Purvine, Samuel O. and Wu, Si and Brewer, Heather M. and Pasa-Tolic, Ljiljana and Bandeira, Nuno and Moore, Bradley S. and Pevzner, Pavel A. and Dorrestein, Pieter C.},
abstractNote = {Ribosomally synthesized and posttranslationally modified peptides (RiPPs), especially from microbial sources, are a large group of bioactive natural products that are a promising source of new (bio)chemistry and bioactivity (1). In light of exponentially increasing microbial genome databases and improved mass spectrometry (MS)-based metabolomic platforms, there is a need for computational tools that connect natural product genotypes predicted from microbial genome sequences with their corresponding chemotypes from metabolomic datasets. Here, we introduce RiPPquest, a tandem mass spectrometry database search tool for identification of microbial RiPPs and apply it for lanthipeptide discovery. RiPPquest uses genomics to limit search space to the vicinity of RiPP biosynthetic genes and proteomics to analyze extensive peptide modifications and compute p-values of peptide-spectrum matches (PSMs). We highlight RiPPquest by connection of multiple RiPPs from extracts of Streptomyces to their gene clusters and by the discovery of a new class III lanthipeptide, informatipeptin, from Streptomyces viridochromogenes DSM 40736 as the first natural product to be identified in an automated fashion by genome mining. The presented tool is available at cy-clo.ucsd.edu.},
doi = {10.1021/cb500199h},
url = {https://www.osti.gov/biblio/1171294}, journal = {ACS Chemical Biology, 9(7):1545-1551},
number = ,
volume = ,
place = {United States},
year = {2014},
month = {7}
}