In:
PLOS Biology, Public Library of Science (PLoS), Vol. 18, No. 12 ( 2020-12-22), p. e3001026-
Kurzfassung:
Microbial natural products constitute a wide variety of chemical compounds, many which can have antibiotic, antiviral, or anticancer properties that make them interesting for clinical purposes. Natural product classes include polyketides (PKs), nonribosomal peptides (NRPs), and ribosomally synthesized and post-translationally modified peptides (RiPPs). While variants of biosynthetic gene clusters (BGCs) for known classes of natural products are easy to identify in genome sequences, BGCs for new compound classes escape attention. In particular, evidence is accumulating that for RiPPs, subclasses known thus far may only represent the tip of an iceberg. Here, we present decRiPPter (Data-driven Exploratory Class-independent RiPP TrackER), a RiPP genome mining algorithm aimed at the discovery of novel RiPP classes. DecRiPPter combines a Support Vector Machine (SVM) that identifies candidate RiPP precursors with pan-genomic analyses to identify which of these are encoded within operon-like structures that are part of the accessory genome of a genus. Subsequently, it prioritizes such regions based on the presence of new enzymology and based on patterns of gene cluster and precursor peptide conservation across species. We then applied decRiPPter to mine 1,295 Streptomyces genomes, which led to the identification of 42 new candidate RiPP families that could not be found by existing programs. One of these was studied further and elucidated as a representative of a novel subfamily of lanthipeptides, which we designate class V. The 2D structure of the new RiPP, which we name pristinin A3 ( 1 ), was solved using nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS) data, and chemical labeling. Two previously unidentified modifying enzymes are proposed to create the hallmark lanthionine bridges. Taken together, our work highlights how novel natural product families can be discovered by methods going beyond sequence similarity searches to integrate multiple pathway discovery criteria.
Materialart:
Online-Ressource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001026
DOI:
10.1371/journal.pbio.3001026.g001
DOI:
10.1371/journal.pbio.3001026.g002
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10.1371/journal.pbio.3001026.g003
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10.1371/journal.pbio.3001026.g004
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10.1371/journal.pbio.3001026.t001
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10.1371/journal.pbio.3001026.t002
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10.1371/journal.pbio.3001026.t003
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10.1371/journal.pbio.3001026.t004
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10.1371/journal.pbio.3001026.s001
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10.1371/journal.pbio.3001026.s002
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10.1371/journal.pbio.3001026.s003
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10.1371/journal.pbio.3001026.s004
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10.1371/journal.pbio.3001026.s005
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10.1371/journal.pbio.3001026.s006
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10.1371/journal.pbio.3001026.s007
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10.1371/journal.pbio.3001026.s008
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10.1371/journal.pbio.3001026.s009
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10.1371/journal.pbio.3001026.s010
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10.1371/journal.pbio.3001026.s011
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10.1371/journal.pbio.3001026.s012
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10.1371/journal.pbio.3001026.s013
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10.1371/journal.pbio.3001026.s014
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10.1371/journal.pbio.3001026.s015
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10.1371/journal.pbio.3001026.s016
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10.1371/journal.pbio.3001026.s017
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10.1371/journal.pbio.3001026.s018
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10.1371/journal.pbio.3001026.s019
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10.1371/journal.pbio.3001026.s020
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10.1371/journal.pbio.3001026.s021
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10.1371/journal.pbio.3001026.s022
DOI:
10.1371/journal.pbio.3001026.s023
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10.1371/journal.pbio.3001026.s024
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10.1371/journal.pbio.3001026.s025
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10.1371/journal.pbio.3001026.s026
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10.1371/journal.pbio.3001026.s027
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10.1371/journal.pbio.3001026.s028
DOI:
10.1371/journal.pbio.3001026.s029
DOI:
10.1371/journal.pbio.3001026.r001
DOI:
10.1371/journal.pbio.3001026.r002
DOI:
10.1371/journal.pbio.3001026.r003
DOI:
10.1371/journal.pbio.3001026.r004
DOI:
10.1371/journal.pbio.3001026.r005
DOI:
10.1371/journal.pbio.3001026.r006
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2020
ZDB Id:
2126773-X
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