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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
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 | |||||||||||||||
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| Subjects: | Q Science > QK Botany R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > 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: |
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| 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: |
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