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Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides

Microbial natural products are a major source of bioactive compounds for drug discovery. Among these molecules, nonribosomal peptides (NRPs) represent a diverse class of natural products that include antibiotics, immunosuppressants, and anticancer agents. Recent breakthroughs in natural product disc...

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Autores principales: Kunyavskaya, Olga, Tagirdzhanov, Azat M., Caraballo-Rodríguez, Andrés Mauricio, Nothias, Louis-Félix, Dorrestein, Pieter C., Korobeynikov, Anton, Mohimani, Hosein, Gurevich, Alexey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541647/
https://www.ncbi.nlm.nih.gov/pubmed/34677408
http://dx.doi.org/10.3390/metabo11100693
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author Kunyavskaya, Olga
Tagirdzhanov, Azat M.
Caraballo-Rodríguez, Andrés Mauricio
Nothias, Louis-Félix
Dorrestein, Pieter C.
Korobeynikov, Anton
Mohimani, Hosein
Gurevich, Alexey
author_facet Kunyavskaya, Olga
Tagirdzhanov, Azat M.
Caraballo-Rodríguez, Andrés Mauricio
Nothias, Louis-Félix
Dorrestein, Pieter C.
Korobeynikov, Anton
Mohimani, Hosein
Gurevich, Alexey
author_sort Kunyavskaya, Olga
collection PubMed
description Microbial natural products are a major source of bioactive compounds for drug discovery. Among these molecules, nonribosomal peptides (NRPs) represent a diverse class of natural products that include antibiotics, immunosuppressants, and anticancer agents. Recent breakthroughs in natural product discovery have revealed the chemical structure of several thousand NRPs. However, biosynthetic gene clusters (BGCs) encoding them are known only for a few hundred compounds. Here, we developed Nerpa, a computational method for the high-throughput discovery of novel BGCs responsible for producing known NRPs. After searching 13,399 representative bacterial genomes from the RefSeq repository against 8368 known NRPs, Nerpa linked 117 BGCs to their products. We further experimentally validated the predicted BGC of ngercheumicin from Photobacterium galatheae via mass spectrometry. Nerpa supports searching new genomes against thousands of known NRP structures, and novel molecular structures against tens of thousands of bacterial genomes. The availability of these tools can enhance our understanding of NRP synthesis and the function of their biosynthetic enzymes.
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spelling pubmed-85416472021-10-24 Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides Kunyavskaya, Olga Tagirdzhanov, Azat M. Caraballo-Rodríguez, Andrés Mauricio Nothias, Louis-Félix Dorrestein, Pieter C. Korobeynikov, Anton Mohimani, Hosein Gurevich, Alexey Metabolites Article Microbial natural products are a major source of bioactive compounds for drug discovery. Among these molecules, nonribosomal peptides (NRPs) represent a diverse class of natural products that include antibiotics, immunosuppressants, and anticancer agents. Recent breakthroughs in natural product discovery have revealed the chemical structure of several thousand NRPs. However, biosynthetic gene clusters (BGCs) encoding them are known only for a few hundred compounds. Here, we developed Nerpa, a computational method for the high-throughput discovery of novel BGCs responsible for producing known NRPs. After searching 13,399 representative bacterial genomes from the RefSeq repository against 8368 known NRPs, Nerpa linked 117 BGCs to their products. We further experimentally validated the predicted BGC of ngercheumicin from Photobacterium galatheae via mass spectrometry. Nerpa supports searching new genomes against thousands of known NRP structures, and novel molecular structures against tens of thousands of bacterial genomes. The availability of these tools can enhance our understanding of NRP synthesis and the function of their biosynthetic enzymes. MDPI 2021-10-11 /pmc/articles/PMC8541647/ /pubmed/34677408 http://dx.doi.org/10.3390/metabo11100693 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kunyavskaya, Olga
Tagirdzhanov, Azat M.
Caraballo-Rodríguez, Andrés Mauricio
Nothias, Louis-Félix
Dorrestein, Pieter C.
Korobeynikov, Anton
Mohimani, Hosein
Gurevich, Alexey
Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides
title Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides
title_full Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides
title_fullStr Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides
title_full_unstemmed Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides
title_short Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides
title_sort nerpa: a tool for discovering biosynthetic gene clusters of bacterial nonribosomal peptides
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541647/
https://www.ncbi.nlm.nih.gov/pubmed/34677408
http://dx.doi.org/10.3390/metabo11100693
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