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Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12031-6. doi: 10.1073/pnas.1406418111. Epub 2014 Aug 4.

Structural investigation of ribosomally synthesized natural products by hypothetical structure enumeration and evaluation using tandem MS.

Author information

1
Howard Hughes Medical Institute,Departments of Chemistry.
2
Howard Hughes Medical Institute,Biochemistry, and.
3
Departments of Chemistry,Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
4
Departments of Chemistry,Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801Microbiology, and.
5
Howard Hughes Medical Institute,Departments of Chemistry,Biochemistry, andInstitute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801 vddonk@illinois.edu.

Abstract

Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a growing class of natural products that are found in all domains of life. These compounds possess vast structural diversity and have a wide range of biological activities, promising a fertile ground for exploring novel natural products. One challenging aspect of RiPP research is the difficulty of structure determination due to their architectural complexity. We here describe a method for automated structural characterization of RiPPs by tandem mass spectrometry. This method is based on the combined analysis of multiple mass spectra and evaluation of a collection of hypothetical structures predicted based on the biosynthetic gene cluster and molecular weight. We show that this method is effective in structural characterization of complex RiPPs, including lanthipeptides, glycopeptides, and azole-containing peptides. Using this method, we have determined the structure of a previously structurally uncharacterized lanthipeptide, prochlorosin 1.2, and investigated the order of the posttranslational modifications in three biosynthetic systems.

KEYWORDS:

dehydration; directionality; genome mining; lantibiotics

PMID:
25092299
PMCID:
PMC4143002
DOI:
10.1073/pnas.1406418111
[Indexed for MEDLINE]
Free PMC Article

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