Automated Genome Mining of Ribosomal Peptide Natural Products

Overview

Journal ACS Chem Biol

Publisher American Chemical Society

Specialties Biochemistry
Biology

Date 2014 May 8

PMID 24802639

Citations 71

Authors

Hosein Mohimani

Roland D Kersten

Wei-Ting Liu

Mingxun Wang

Samuel O Purvine

Si Wu

Heather M Brewer

Ljiljana Pasa-Tolic

Nuno Bandeira

Bradley S Moore

Pavel A Pevzner

Pieter C Dorrestein

Affiliations

Soon will be listed here.

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 data sets. Here, we introduce RiPPquest, a tandem mass spectrometry database search tool for identification of microbial RiPPs, and apply it to 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 connecting 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 to reflect that it is a natural product that was discovered by mass spectrometry based genome mining using algorithmic tools rather than manual inspection of mass spectrometry data and genetic information. The presented tool is available at cyclo.ucsd.edu.

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References

Kelly R, Page J, Luo Q, Moore R, Orton D, Tang K . Chemically etched open tubular and monolithic emitters for nanoelectrospray ionization mass spectrometry. Anal Chem. 2006; 78(22):7796-801. PMC: 1769309. DOI: 10.1021/ac061133r. View

Willey J, van der Donk W . Lantibiotics: peptides of diverse structure and function. Annu Rev Microbiol. 2007; 61:477-501. DOI: 10.1146/annurev.micro.61.080706.093501. View

McClerren A, Cooper L, Quan C, Thomas P, Kelleher N, van der Donk W . Discovery and in vitro biosynthesis of haloduracin, a two-component lantibiotic. Proc Natl Acad Sci U S A. 2006; 103(46):17243-8. PMC: 1859917. DOI: 10.1073/pnas.0606088103. View

Frank A, Pevzner P . PepNovo: de novo peptide sequencing via probabilistic network modeling. Anal Chem. 2005; 77(4):964-73. DOI: 10.1021/ac048788h. View

Arnison P, Bibb M, Bierbaum G, Bowers A, Bugni T, Bulaj G . Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep. 2012; 30(1):108-60. PMC: 3954855. DOI: 10.1039/c2np20085f. View

Pevzner P, Mulyukov Z, Dancik V, Tang C . Efficiency of database search for identification of mutated and modified proteins via mass spectrometry. Genome Res. 2001; 11(2):290-9. PMC: 544186. DOI: 10.1101/gr.154101. View

Mohimani H, Liu W, Mylne J, Poth A, Colgrave M, Tran D . Cycloquest: identification of cyclopeptides via database search of their mass spectra against genome databases. J Proteome Res. 2011; 10(10):4505-12. PMC: 3242011. DOI: 10.1021/pr200323a. View

van Heel A, de Jong A, Montalban-Lopez M, Kok J, Kuipers O . BAGEL3: Automated identification of genes encoding bacteriocins and (non-)bactericidal posttranslationally modified peptides. Nucleic Acids Res. 2013; 41(Web Server issue):W448-53. PMC: 3692055. DOI: 10.1093/nar/gkt391. View

Kersten R, Yang Y, Xu Y, Cimermancic P, Nam S, Fenical W . A mass spectrometry-guided genome mining approach for natural product peptidogenomics. Nat Chem Biol. 2011; 7(11):794-802. PMC: 3258187. DOI: 10.1038/nchembio.684. View

10.

Medema M, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach M . antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res. 2011; 39(Web Server issue):W339-46. PMC: 3125804. DOI: 10.1093/nar/gkr466. View

11.

Tsur D, Tanner S, Zandi E, Bafna V, Pevzner P . Identification of post-translational modifications by blind search of mass spectra. Nat Biotechnol. 2005; 23(12):1562-7. DOI: 10.1038/nbt1168. View

12.

Bandeira N, Tsur D, Frank A, Pevzner P . Protein identification by spectral networks analysis. Proc Natl Acad Sci U S A. 2007; 104(15):6140-5. PMC: 1851064. DOI: 10.1073/pnas.0701130104. View

13.

Duncan M, Aebersold R, Caprioli R . The pros and cons of peptide-centric proteomics. Nat Biotechnol. 2010; 28(7):659-64. DOI: 10.1038/nbt0710-659. View

14.

Watrous J, Roach P, Alexandrov T, Heath B, Yang J, Kersten R . Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci U S A. 2012; 109(26):E1743-52. PMC: 3387089. DOI: 10.1073/pnas.1203689109. View

15.

Begley M, Cotter P, Hill C, Ross R . Identification of a novel two-peptide lantibiotic, lichenicidin, following rational genome mining for LanM proteins. Appl Environ Microbiol. 2009; 75(17):5451-60. PMC: 2737927. DOI: 10.1128/AEM.00730-09. View

16.

Zerikly M, Challis G . Strategies for the discovery of new natural products by genome mining. Chembiochem. 2009; 10(4):625-33. DOI: 10.1002/cbic.200800389. View

17.

Ueda K, Oinuma K, Ikeda G, Hosono K, Ohnishi Y, Horinouchi S . AmfS, an extracellular peptidic morphogen in Streptomyces griseus. J Bacteriol. 2002; 184(5):1488-92. PMC: 134859. DOI: 10.1128/JB.184.5.1488-1492.2002. View

18.

Voller G, Krawczyk B, Ensle P, Sussmuth R . Involvement and unusual substrate specificity of a prolyl oligopeptidase in class III lanthipeptide maturation. J Am Chem Soc. 2013; 135(20):7426-9. DOI: 10.1021/ja402296m. View

19.

Meindl K, Schmiederer T, Schneider K, Reicke A, Butz D, Keller S . Labyrinthopeptins: a new class of carbacyclic lantibiotics. Angew Chem Int Ed Engl. 2010; 49(6):1151-4. DOI: 10.1002/anie.200905773. View

20.

Nguyen D, Wu C, Moree W, Lamsa A, Medema M, Zhao X . MS/MS networking guided analysis of molecule and gene cluster families. Proc Natl Acad Sci U S A. 2013; 110(28):E2611-20. PMC: 3710860. DOI: 10.1073/pnas.1303471110. View