Details
| Original language | English |
|---|---|
| Article number | 25202 |
| Journal | Scientific reports |
| Volume | 6 |
| Publication status | Published - 4 May 2016 |
| Externally published | Yes |
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.
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In: Scientific reports, Vol. 6, 25202, 04.05.2016.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production
AU - Bailey, Andy M.
AU - Alberti, Fabrizio
AU - Kilaru, Sreedhar
AU - Collins, Catherine M.
AU - De Mattos-Shipley, Kate
AU - Hartley, Amanda J.
AU - Hayes, Patrick
AU - Griffin, Alison
AU - Lazarus, Colin M.
AU - Cox, Russell J.
AU - Willis, Christine L.
AU - O'Dwyer, Karen
AU - Spence, David W.
AU - Foster, Gary D.
N1 - Funding information: Much of this work was a follow on from BBSRC grant award to develop a Basidio Molecular Toolkit D19266. K.de M.-S. was supported through a BBSRC-G.S.K. CASE Award BB/E528379/1. P.H. and F.A. were both supported through University of Bristol Awards. S.K., C.M.C. and A.J.H. were all supported though funding from G.S.K. to the University of Bristol. Chemical analysis was performed on equipment provided by EPSRC EP/F066104/1 We also wish to thank Dr. Craig Butts for help with acquiring 500 MHz NMR data and Dr. Paul Gates from Bristol University Mass Spectrometry Service for help with obtaining HRMS data.
PY - 2016/5/4
Y1 - 2016/5/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84965104303&partnerID=8YFLogxK
U2 - 10.1038/srep25202
DO - 10.1038/srep25202
M3 - Article
C2 - 27143514
AN - SCOPUS:84965104303
VL - 6
JO - Scientific reports
JF - Scientific reports
SN - 2045-2322
M1 - 25202
ER -