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The zinc bound form of the actinomycete derived natural product compound JBIR-141 induces a mitotic phenotype in fission yeast

Lewis, Richard Alexander, Hayles, Jacqueline, Hall, Michael John, Gray, Joe, Mebrate, Sofanit, Li, Juanjuan, Allenby, Nicholas Edward Ellis and Errington, Jeff (2025) The zinc bound form of the actinomycete derived natural product compound JBIR-141 induces a mitotic phenotype in fission yeast. Scientific Reports, 15 (1): 39721. p. 39721. ISSN 2045-2322

Item Type: Article

Abstract

This study was designed to identify the natural product compound produced by the actinomycete strain “S149” which is capable of inducing a strong small cell phenotype, called wee, in the fission yeast Schizosaccharomyces pombe. We purified the bioactive molecule, which, on the basis of mass spectrometry data, was identified as a novel zinc-bound form of the previously published molecule JBIR-141. JBIR-141 was not previously known to be a zincophore and does not possess structural features common to other bacterial zinc-binding natural product compounds. Testing the effect of the Zn2+ bound form of JBIR-14 against a series of S. pombe deletion mutants which express a wee phenotype suggested its potential target in fission yeast is either Pyp1, which is involved in regulation of the onset of mitosis, an important control in the eukaryotic cell cycle, or an element in the Pyp1 signalling pathway.

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Additional Information: ** From Springer Nature via Jisc Publications Router ** History: received 12-06-2025; registration 06-10-2025; accepted 06-10-2025; epub 12-11-2025; online 12-11-2025; collection 01-12-2025. ** Licence for this article: http://creativecommons.org/licenses/by-nc-nd/4.0/ ** Acknowledgements: We thank Dr B. Hover and Dr N. Dales of Odyssey Therapeutics Inc for permission to publish and J. Devi for scientific discussions.
Uncontrolled Keywords: Zincophore, Pyp1, JBIR-141, Zinc, Fission yeast
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Identifiers

Item ID: 19648
Identification Number: 10.1038/s41598-025-23271-w
ISSN: 2045-2322
URI: https://sure.sunderland.ac.uk/id/eprint/19648
Official URL: https://www.nature.com/articles/s41598-025-23271-w

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Catalogue record

Date Deposited: 29 Nov 2025 14:25
Last Modified: 29 Nov 2025 14:25

Contributors

Author: Richard Alexander Lewis
Author: Jacqueline Hayles
Author: Michael John Hall
Author: Joe Gray
Author: Sofanit Mebrate
Author: Juanjuan Li
Author: Nicholas Edward Ellis Allenby
Author: Jeff Errington

University Divisions

Faculty of Health Sciences and Wellbeing > Pharmacy and Pharmaceutical Sciences

Subjects

Sciences > Pharmacy and Pharmacology

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