2017/11/22 by Fabrizio Alberti, Khairunisa Khairudin, Edith Rodriguez Venegas +5 · 2 citations
Veterinary · Medicine · Pharmacology, Toxicology and Pharmaceutics · #Veterinary medicine and infectious diseases #Mycobacterium research and diagnosis #Pharmacological Effects of Natural Compounds
paper · pdf · doi:10.1038/s41467-017-01659-1
openalex publication_date 2017/11/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
The rise in antibiotic resistance is a major threat for human health. Basidiomycete fungi represent an untapped source of underexploited antimicrobials, with pleuromutilin-a diterpene produced by Clitopilus passeckerianus-being the only antibiotic from these fungi leading to commercial derivatives. Here we report genetic characterisation of the steps involved in pleuromutilin biosynthesis, through rational heterologous expression in Aspergillus oryzae coupled with isolation and detailed structural elucidation of the pathway intermediates by spectroscopic methods and comparison with synthetic standards. A. oryzae was further established as a platform for bio-conversion of chemically modified analogues of pleuromutilin intermediates, and was employed to generate a semi-synthetic pleuromutilin derivative with enhanced antibiotic activity. These studies pave the way for future characterisation of biosynthetic pathways of other basidiomycete natural products in ascomycete heterologous hosts, and open up new possibilities of further chemical modification for the growing class of potent pleuromutilin antibiotics.