Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355

A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces c...

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Autores principales: Kepplinger, Bernhard, Mardiana, Lina, Cowell, Joseph, Morton-Laing, Stephanie, Dashti, Yousef, Wills, Corinne, Marrs, Emma C. L., Perry, John D., Gray, Joe, Goodfellow, Michael, Errington, Jeff, Probert, Michael R., Clegg, William, Bogaerts, Jonathan, Herrebout, Wouter, Allenby, Nick E. E., Hall, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481585/
https://www.ncbi.nlm.nih.gov/pubmed/36114335
http://dx.doi.org/10.1038/s41598-022-18726-3
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author Kepplinger, Bernhard
Mardiana, Lina
Cowell, Joseph
Morton-Laing, Stephanie
Dashti, Yousef
Wills, Corinne
Marrs, Emma C. L.
Perry, John D.
Gray, Joe
Goodfellow, Michael
Errington, Jeff
Probert, Michael R.
Clegg, William
Bogaerts, Jonathan
Herrebout, Wouter
Allenby, Nick E. E.
Hall, Michael J.
author_facet Kepplinger, Bernhard
Mardiana, Lina
Cowell, Joseph
Morton-Laing, Stephanie
Dashti, Yousef
Wills, Corinne
Marrs, Emma C. L.
Perry, John D.
Gray, Joe
Goodfellow, Michael
Errington, Jeff
Probert, Michael R.
Clegg, William
Bogaerts, Jonathan
Herrebout, Wouter
Allenby, Nick E. E.
Hall, Michael J.
author_sort Kepplinger, Bernhard
collection PubMed
description A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152. Structural elucidation, including absolute stereochemical assignment, was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Cytological profiling experiments suggest a putative antibiotic mode-of-action, involving membrane depolarisation and chromosomal decondensation of the target bacteria.
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spelling pubmed-94815852022-09-18 Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355 Kepplinger, Bernhard Mardiana, Lina Cowell, Joseph Morton-Laing, Stephanie Dashti, Yousef Wills, Corinne Marrs, Emma C. L. Perry, John D. Gray, Joe Goodfellow, Michael Errington, Jeff Probert, Michael R. Clegg, William Bogaerts, Jonathan Herrebout, Wouter Allenby, Nick E. E. Hall, Michael J. Sci Rep Article A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152. Structural elucidation, including absolute stereochemical assignment, was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Cytological profiling experiments suggest a putative antibiotic mode-of-action, involving membrane depolarisation and chromosomal decondensation of the target bacteria. Nature Publishing Group UK 2022-09-16 /pmc/articles/PMC9481585/ /pubmed/36114335 http://dx.doi.org/10.1038/s41598-022-18726-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kepplinger, Bernhard
Mardiana, Lina
Cowell, Joseph
Morton-Laing, Stephanie
Dashti, Yousef
Wills, Corinne
Marrs, Emma C. L.
Perry, John D.
Gray, Joe
Goodfellow, Michael
Errington, Jeff
Probert, Michael R.
Clegg, William
Bogaerts, Jonathan
Herrebout, Wouter
Allenby, Nick E. E.
Hall, Michael J.
Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355
title Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355
title_full Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355
title_fullStr Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355
title_full_unstemmed Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355
title_short Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355
title_sort discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from amycolatopsis sp. dem30355
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481585/
https://www.ncbi.nlm.nih.gov/pubmed/36114335
http://dx.doi.org/10.1038/s41598-022-18726-3
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