The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture.
The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture.
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DOI：
10.1021/acs.jnatprod.7b00133
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发表时间：
2017-04-28
影响因子：
5.1
通讯作者：
Klepacki D
中科院分区：
文献类型：
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作者：
Stierle AA;Stierle DB;Decato D;Priestley ND;Alverson JB;Hoody J;McGrath K;Klepacki D
通过对褐色青霉和卡门贝青霉/棒曲霉进行精心定时的共培养发酵，产生了8种新的16元环大环内酯类化合物，伯克基内酯A-H（1，4，6-9，12，13），以及已知的抗生素大环内酯A26771 B（5）、展青霉素和桔霉素。无菌培养时，两种真菌均未产生berkeleylactones或A26771 B（5）。化合物1和9的结构由光谱数据推断，绝对构型由单晶X-射线晶体学确定。Berkeleylactone A（1）在大环内酯系列中表现出最强的抗菌活性，对4种MRSA菌株以及炭疽芽孢杆菌、化脓链球菌、白色念珠菌和光滑念珠菌具有低微摩尔活性（MIC = 1-2 μg/mL）。作用模式研究表明，与其他大环内酯类抗生素不同，berkeleylactone A（1）不抑制蛋白质合成，也不靶向核糖体，这表明其抗生素活性的新作用模式。
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.