Integrating genomics and metabolomics for scalable non-ribosomal peptide discovery.
Algorithms
Amino Acid Sequence
/ genetics
Anti-Bacterial Agents
/ biosynthesis
Biological Products
/ isolation & purification
Computational Biology
/ methods
Datasets as Topic
Drug Discovery
/ methods
Humans
Mass Spectrometry
Metabolic Networks and Pathways
/ genetics
Metabolomics
/ methods
Metagenomics
/ methods
Microbiota
/ genetics
Multigene Family
Peptide Biosynthesis
Peptide Synthases
/ genetics
Peptides
/ genetics
Soil Microbiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 05 2021
28 05 2021
Historique:
received:
23
09
2020
accepted:
04
05
2021
entrez:
29
5
2021
pubmed:
30
5
2021
medline:
9
6
2021
Statut:
epublish
Résumé
Non-Ribosomal Peptides (NRPs) represent a biomedically important class of natural products that include a multitude of antibiotics and other clinically used drugs. NRPs are not directly encoded in the genome but are instead produced by metabolic pathways encoded by biosynthetic gene clusters (BGCs). Since the existing genome mining tools predict many putative NRPs synthesized by a given BGC, it remains unclear which of these putative NRPs are correct and how to identify post-assembly modifications of amino acids in these NRPs in a blind mode, without knowing which modifications exist in the sample. To address this challenge, here we report NRPminer, a modification-tolerant tool for NRP discovery from large (meta)genomic and mass spectrometry datasets. We show that NRPminer is able to identify many NRPs from different environments, including four previously unreported NRP families from soil-associated microbes and NRPs from human microbiota. Furthermore, in this work we demonstrate the anti-parasitic activities and the structure of two of these NRP families using direct bioactivity screening and nuclear magnetic resonance spectrometry, illustrating the power of NRPminer for discovering bioactive NRPs.
Identifiants
pubmed: 34050176
doi: 10.1038/s41467-021-23502-4
pii: 10.1038/s41467-021-23502-4
pmc: PMC8163882
doi:
Substances chimiques
Anti-Bacterial Agents
0
Biological Products
0
Peptides
0
Peptide Synthases
EC 6.3.2.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3225Subventions
Organisme : NIGMS NIH HHS
ID : DP2 GM126893
Pays : United States
Organisme : NIGMS NIH HHS
ID : DP2 GM137413
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Commentaires et corrections
Type : ErratumIn
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