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

authored by

Andy M. Bailey, Fabrizio Alberti, Sreedhar Kilaru, Catherine M. Collins, Kate De Mattos-Shipley, Amanda J. Hartley, Patrick Hayes, Alison Griffin, Colin M. Lazarus, Russell J. Cox, Christine L. Willis, Karen O'Dwyer, David W. Spence, Gary D. Foster

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.

External Organisation(s)

University of Bristol
2GSK
GlaxoSmithKline GmbH and Co. KG

Type

Article

Journal

Scientific reports

Volume

6

ISSN

2045-2322

Publication date

04.05.2016

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

General

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1038/srep25202 (Access: Open)