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

Amycolatopsis Anti-Bacterial Agents / chemistry Methicillin-Resistant Staphylococcus aureus / genetics Polyketides Streptomyces coelicolor / genetics

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
16 09 2022
Historique:
received: 15 06 2022
accepted: 18 08 2022
entrez: 16 9 2022
pubmed: 17 9 2022
medline: 21 9 2022
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-022-18726-3 PMID: 36114335 PMC: PMC9481585
pubmed: 36114335
doi: 10.1038/s41598-022-18726-3
pii: 10.1038/s41598-022-18726-3
pmc: PMC9481585
doi:

Substances chimiques

Anti-Bacterial Agents 0
Polyketides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

15579

Subventions

Organisme : Wellcome Trust
ID : 209500/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 209500
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Bernhard Kepplinger (B)

Biopharmaceutical Bioprocessing Technology Centre, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK. Bernhard.kepplinger@uwr.edu.pl.
Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK. Bernhard.kepplinger@uwr.edu.pl.
Demuris Limited, The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne, NE4 5BX, UK. Bernhard.kepplinger@uwr.edu.pl.
Department of Molecular Microbiology, Faculty of Biotechnology, University of Wrocław, 50-383, Wrocław, Poland. Bernhard.kepplinger@uwr.edu.pl.

Lina Mardiana (L)

Chemistry, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Joseph Cowell (J)

Chemistry, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Stephanie Morton-Laing (S)

Chemistry, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Yousef Dashti (Y)

Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK.

Corinne Wills (C)

Chemistry, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Emma C L Marrs (ECL)

Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK.

John D Perry (JD)

Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK.

Joe Gray (J)

Pinnacle Laboratory, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK.

Michael Goodfellow (M)

Biology, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Jeff Errington (J)

Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK.
Demuris Limited, The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne, NE4 5BX, UK.

Michael R Probert (MR)

Chemistry, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

William Clegg (W)

Chemistry, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Jonathan Bogaerts (J)

Molecular Spectroscopy, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.

Wouter Herrebout (W)

Molecular Spectroscopy, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.

Nick E E Allenby (NEE)

Demuris Limited, The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne, NE4 5BX, UK. nick.allenby@demuris.co.uk.

Michael J Hall (MJ)

Chemistry, School of Environmental and Natural Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK. michael.hall@newcastle.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Actinomycetales › Amycolatopsis › Discovery, isolation, heterologous expression...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › Discovery, isolation, heterologous expression...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Cocci à Gram positif › Staphylococcaceae › Staphylococcus › Staphylococcus aureus › Staphylococcus aureus résistant à la méticilline › Discovery, isolation, heterologous expression...
questionsmedicales.fr › Composés polycycliques › Composés macrocycliques › Polycétides › Discovery, isolation, heterologous expression...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets sporulés à Gram positif › Streptomycetaceae › Streptomyces › Streptomyces coelicolor › Discovery, isolation, heterologous expression...