Forazoline A: marine-derived polyketide with antifungal in vivo efficacy.
Forazoline A: marine-derived polyketide with antifungal in vivo efficacy.
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DOI：
10.1002/anie.201405990
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发表时间：
2014-10-20
影响因子：
16.6
通讯作者：
Bugni, Tim S
中科院分区：
文献类型：
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作者：
Wyche, Thomas P;Piotrowski, Jeff S;Hou, Yanpeng;Braun, Doug;Deshpande, Raamesh;McIlwain, Sean;Ong, Irene M;Myers, Chad L;Guzei, Ilia A;Westler, William M;Andes, David R;Bugni, Tim S
Forazoline A是一种新型的抗真菌多酮化合物，具有体内抗白色念珠菌的作用，利用基于LC MS的代谢组学方法研究海洋无脊椎动物相关细菌。Forazoline A有一个非常不寻常和史无前例的骨骼。获得13C-13C gCOSY和13C-15N HMQCNMR实验分别提供了直接的碳-碳和碳-氮连接性；这是确定天然产品的直接13C-15N连接性的第一个例子。利用酵母化学基因组学，我们认为Forazoline A通过一种新的作用机制发挥作用，其表型结果是破坏膜的完整性。
Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS-based metabolomics to investigate marine invertebrate-associated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of 13C-13C gCOSY and 13C-15N HMQCNMR experiments provided the direct carbon-carbon and carbon-nitrogen connectivity, respectively; this represents the first example of determining direct 13C-15N connectivity for a natural product. Using yeast chemical genomics, we propose that forazoline A works via a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.