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Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria

Streptomyces bacteria are known for their prolific production of secondary metabolites, many of which have been widely used in human medicine, agriculture and animal health. To guide the effective prioritization of specific biosynthetic gene clusters (BGCs) for drug development and targeting the mos...

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Autores principales: Belknap, Kaitlyn C., Park, Cooper J., Barth, Brian M., Andam, Cheryl P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005152/
https://www.ncbi.nlm.nih.gov/pubmed/32029878
http://dx.doi.org/10.1038/s41598-020-58904-9
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author Belknap, Kaitlyn C.
Park, Cooper J.
Barth, Brian M.
Andam, Cheryl P.
author_facet Belknap, Kaitlyn C.
Park, Cooper J.
Barth, Brian M.
Andam, Cheryl P.
author_sort Belknap, Kaitlyn C.
collection PubMed
description Streptomyces bacteria are known for their prolific production of secondary metabolites, many of which have been widely used in human medicine, agriculture and animal health. To guide the effective prioritization of specific biosynthetic gene clusters (BGCs) for drug development and targeting the most prolific producer strains, knowledge about phylogenetic relationships of Streptomyces species, genome-wide diversity and distribution patterns of BGCs is critical. We used genomic and phylogenetic methods to elucidate the diversity of major classes of BGCs in 1,110 publicly available Streptomyces genomes. Genome mining of Streptomyces reveals high diversity of BGCs and variable distribution patterns in the Streptomyces phylogeny, even among very closely related strains. The most common BGCs are non-ribosomal peptide synthetases, type 1 polyketide synthases, terpenes, and lantipeptides. We also found that numerous Streptomyces species harbor BGCs known to encode antitumor compounds. We observed that strains that are considered the same species can vary tremendously in the BGCs they carry, suggesting that strain-level genome sequencing can uncover high levels of BGC diversity and potentially useful derivatives of any one compound. These findings suggest that a strain-level strategy for exploring secondary metabolites for clinical use provides an alternative or complementary approach to discovering novel pharmaceutical compounds from microbes.
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spelling pubmed-70051522020-02-18 Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria Belknap, Kaitlyn C. Park, Cooper J. Barth, Brian M. Andam, Cheryl P. Sci Rep Article Streptomyces bacteria are known for their prolific production of secondary metabolites, many of which have been widely used in human medicine, agriculture and animal health. To guide the effective prioritization of specific biosynthetic gene clusters (BGCs) for drug development and targeting the most prolific producer strains, knowledge about phylogenetic relationships of Streptomyces species, genome-wide diversity and distribution patterns of BGCs is critical. We used genomic and phylogenetic methods to elucidate the diversity of major classes of BGCs in 1,110 publicly available Streptomyces genomes. Genome mining of Streptomyces reveals high diversity of BGCs and variable distribution patterns in the Streptomyces phylogeny, even among very closely related strains. The most common BGCs are non-ribosomal peptide synthetases, type 1 polyketide synthases, terpenes, and lantipeptides. We also found that numerous Streptomyces species harbor BGCs known to encode antitumor compounds. We observed that strains that are considered the same species can vary tremendously in the BGCs they carry, suggesting that strain-level genome sequencing can uncover high levels of BGC diversity and potentially useful derivatives of any one compound. These findings suggest that a strain-level strategy for exploring secondary metabolites for clinical use provides an alternative or complementary approach to discovering novel pharmaceutical compounds from microbes. Nature Publishing Group UK 2020-02-06 /pmc/articles/PMC7005152/ /pubmed/32029878 http://dx.doi.org/10.1038/s41598-020-58904-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Belknap, Kaitlyn C.
Park, Cooper J.
Barth, Brian M.
Andam, Cheryl P.
Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria
title Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria
title_full Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria
title_fullStr Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria
title_full_unstemmed Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria
title_short Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria
title_sort genome mining of biosynthetic and chemotherapeutic gene clusters in streptomyces bacteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005152/
https://www.ncbi.nlm.nih.gov/pubmed/32029878
http://dx.doi.org/10.1038/s41598-020-58904-9
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