The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture

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.

Loci Encoding Compounds Potentially Active against Drug-Resistant Pathogens amidst a Decreasing Pool of Novel Antibiotics

“…protegens strains to produce pyoluteorin (56). This type of cooperative regulation among organisms has also been observed among fungi (57). Penicillium fuscum and Penicillium camemberti / P.…”

Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics

“…X-ray crystallography was also used to determine the absolute configuration of several 12-, 14-, and 16-membered macrolide compounds isolated from fungi species [ 36 , 37 , 38 ]. Bastimolide A, a polyhydroxy macrolide with a 40-membered ring isolated from cyanobacterium Okeania hirsuta was structurally characterized by X-ray diffraction analysis, and its absolute conformation was determined [ 39 ].…”

A Decade of Antifungal Leads from Natural Products: 2010–2019

“…Coculture of two extremophilic fungal strains of Penicillium fuscum (Sopp) Raper & Thom and Penicillium camembertii/clavigerum Thom isolated from a single sample of surface water from Berkeley Pit Lake led to the production of novel metabolites. Berkeleylactone A (81) displayed modest antifungal activity with an IC 50 of 6 µg/mL against C. glabrata and higher antibacterial activity [68]. Fermentation of a Saudi strain of Petriella setifera led to the identification of the triterpene glycoside amnomopin (82) with MIC values of 0.5-2 µg/mL against Candida species [69].…”