Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.
Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.
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DOI：
10.1021/acs.jnatprod.0c00641
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发表时间：
2020-09-25
影响因子：
5.1
通讯作者：
Bills GF
中科院分区：
文献类型：
--
作者：
Perlatti B;Harris G;Nichols CB;Ekanayake DI;Alspaugh JA;Gloer JB;Bills GF
Campafungin A是一种聚酮化合物，由于其抗增殖和抗菌丝活性而在白色念珠菌适应性试验中被识别。假设其作用模式涉及cAMP依赖性PKA途径的抑制。最初提出的结构似乎需要以某种不寻常的方式组装聚酮化合物。然而，结构表征数据从未正式发表。这一背景刺激了重新研究，其中从子囊菌真菌Plenodomus enteroleucus菌株的发酵物中纯化了白曲霉素A和三种密切相关的次要成分。标记研究，沿着广泛的NMR分析，使得能够分配与常规聚酮化合物合成机器一致的修订结构。本研究中遇到的阿霉素A和新的类似物，在这里指定为阿霉素B，C和D的结构解析，提出了沿着提出的生物合成路线。抗菌谱扩大到耐甲氧西林金黄色葡萄球菌、热带念珠菌、光滑念珠菌、新型隐球菌、烟曲霉和粟酒裂殖酵母，在C中的MIC范围低至4-8 μg mL−1。新人类使用C.新变形杆菌突变体表明多种途径受到影响，但PKA/cAMP途径的突变体不受影响，表明作用模式与在C.白色念珠菌
Campafungin A is a polyketide that was recognized in the Candida albicans fitness test due to its antiproliferative and antihyphal activity. Its mode of action was hypothesized to involve inhibition of a cAMP-dependent PKA pathway. The originally proposed structure appeared to require a polyketide assembled in a somewhat unusual fashion. However, structural characterization data were never formally published. This background stimulated a reinvestigation in which campafungin A and three closely related minor constituents were purified from fermentations of a strain of the ascomycete fungus Plenodomus enteroleucus. Labeling studies, along with extensive NMR analysis, enabled assignment of a revised structure consistent with conventional polyketide synthetic machinery. The structure elucidation of campafungin A and new analogues encountered in this study, designated here as campafungins B, C, and D, is presented, along with a proposed biosynthetic route. The antimicrobial spectrum was expanded to methicillin-resistant Staphylococcus aureus, Candida tropicalis, Candida glabrata, Cryptococcus neoformans, Aspergillus fumigatus, and Schizosaccharomyces pombe, with MICs ranging as low as 4–8 μg mL−1 in C. neoformans. Mode-of-action studies employing libraries of C. neoformans mutants indicated that multiple pathways were affected, but mutants in PKA/cAMP pathways were unaffected, indicating that the mode of action was distinct from that observed in C. albicans.
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影响因子：
64.5
作者：
Liu OW;Chun CD;Chow ED;Chen C;Madhani HD;Noble SM
通讯作者：
Noble SM
影响因子：
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通讯作者：
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作者：
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通讯作者：
Vicente, Francisca
影响因子：
3.5
作者：
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通讯作者：
Singh, Sheo B.