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Discovery, Isolation, Heterologous Expression and Mode-of Action Studies of the Antibiotic Polyketide Tatiomicin from Amycolatopsis sp. DEM30355

Lookup NU author(s): Dr Bernhard Kepplinger, Lina Mardiana, Joseph Cowell, Dr Stephanie Morton-Laing, Dr Yousef Dashti, Dr Corinne Wills, Dr John Perry, Professor Michael Goodfellow, Professor Jeff Errington, Professor Mike ProbertORCiD, Professor William Clegg, Dr Nicholas Allenby, Dr Michael HallORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

Author(s): Kepplinger B, Mardiana L, Cowell J, Morton-Laing S, Dashti Y, Wills C, Marrs ECL, Perry JD, Gray J, Goodfellow M, Errington J, Probert MR, Clegg W, Bogaerts J, Herrebout W, Allenby N, Hall MJ

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2022

Volume: 12

Online publication date: 16/09/2022

Acceptance date: 18/08/2022

Date deposited: 06/09/2022

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41598-022-18726-3

DOI: 10.1038/s41598-022-18726-3


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Funding

Funder referenceFunder name
100953
1198318N
131143
209500
EP/G037620/1Alcyomics Ltd
EP/G037620/1BOC Group Limited
M543
MT11145
MT6749

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