The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture

Andrea A. Stierle, Donald B. Stierle, Daniel Decato, Nigel D. Priestley, Jeremy B. Alverson, John Hoody, Kelly McGrath, Dorota Klepacki

Research output: Contribution to journalArticlepeer-review

Abstract

A carefully timed coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded eight new 16-membered-ring macrolides, berkeleylactones A-H (1, 4, 6-9, 12, 13), as well as the known antibiotic macrolide A26771B (5), patulin, and citrinin. There was no evidence of the production of the berkeleylactones or A26771B (5) by either fungus when grown as axenic cultures. The structures were deduced from analyses of spectral data, and the absolute configurations of compounds 1 and 9 were determined by single-crystal X-ray crystallography. Berkeleylactone A (1) exhibited the most potent antimicrobial activity of the macrolide series, with low micromolar activity (MIC = 1-2 μg/mL) against four MRSA strains, as well as Bacillus anthracis, Streptococcus pyogenes, Candida albicans, and Candida glabrata. Mode of action studies have shown that, unlike other macrolide antibiotics, berkeleylactone A (1) does not inhibit protein synthesis nor target the ribosome, which suggests a novel mode of action for its antibiotic activity.

Original languageEnglish
Pages (from-to)1150-1160
Number of pages11
JournalJournal of Natural Products
Volume80
Issue number4
DOIs
StatePublished - Apr 28 2017

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