2016/05/04 by Andy M. Bailey, Fabrizio Alberti, Sreedhar Kilaru +11 · 3 citations
Immunology and Microbiology · Pharmacology, Toxicology and Pharmaceutics · Veterinary · #Antibiotics #Biology #Biotechnology #Botany #Computational biology #Fungus #Gene #Gene cluster #Genetics #Microbiology #Pharmacological Effects of Natural Compounds #Toxin Mechanisms and Immunotoxins #Veterinary medicine and infectious diseases
paper · pdf · doi:10.1038/srep25202
openalex publication_date 2016/05/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.