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Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

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Bailey, Andy M., Alberti, Fabrizio, Kilaru, Sreedhar, Collins, Catherine M., de Mattos-Shipley, Kate, Hartley, Amanda J., Hayes, Patrick, Griffin, Alison, Lazarus, Colin M., Cox, Russell J., Willis, Christine L., O’Dwyer, Karen, Spence, David W. and Foster, Gary D. (2016) Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production. Scientific Reports, 6 (1). doi:10.1038/srep25202

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Official URL: http://dx.doi.org/10.1038/srep25202

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Abstract

Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi.

Item Type: Journal Article
Subjects: Q Science > QK Botany
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Antibiotic-producing organisms, Fungal metabolites, Basidiomycetes, Antibiotics -- Synthesis, Drug resistance in microorganisms
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group
ISSN: 2045-2322
Official Date: 4 May 2016
Dates:
DateEvent
4 May 2016Published
11 April 2016Accepted
18 February 2016Submitted
Volume: 6
Number: 1
DOI: 10.1038/srep25202
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/E528379/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDUniversity of Bristolhttp://dx.doi.org/10.13039/501100000883
UNSPECIFIEDGlaxoSmithKlinehttp://dx.doi.org/10.13039/100004330
EP/F066104/1Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266

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