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Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production
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Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production
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Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production
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Journal Article
Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38
/ 38/23
/ 38/39
/ 38/70
/ 45
/ 82
/ 82/6
/ 82/80
/ Anti-Bacterial Agents - biosynthesis
/ Aspergillus oryzae - genetics
/ Aspergillus oryzae - metabolism
/ Biosynthetic Pathways - genetics
/ Fungi
/ Humanities and Social Sciences
/ Recombinant Proteins - genetics
/ Recombinant Proteins - metabolism
/ Science
