Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, United States.
J Nat Prod. 2014 Jun 27;77(6):1280-6. doi: 10.1021/np401019t. Epub 2014 Jun 16.
The Candida albicans fitness test is a whole cell screening platform that utilizes a mixed-pool of C. albicans mutants, each of which carries a heterozygous deletion of a particular gene. In the presence of an antifungal inhibitor, a subset of these mutants exhibits a growth phenotype of hypersensitivity or hyposensitivity. Collectively these mutants reflect aspects of the mechanism of action of the compound in question. In the course of screening natural products a culture of Streptomyces sp. MS-1-4 was discovered to produce a compound, dretamycin, which yielded a fitness profile exhibiting significant hypersensitivity of the DRE2 heterozygote and hyposensitivity of the DIP5 heterozygote. Herein we report the production, isolation, and structure elucidation of dretamycin.
白色念珠菌适应度测试是一种全细胞筛选平台，利用了混合池的白色念珠菌突变体，每个突变体都携带特定基因的杂合缺失。在抗真菌抑制剂存在的情况下，这些突变体中的一部分表现出超敏或低敏的生长表型。这些突变体共同反映了该化合物作用机制的某些方面。在筛选天然产物的过程中，发现了一株放线菌 sp. MS-1-4 产生一种化合物，dretamycin，它的适应度谱表现出 DRE2 杂合子的显著超敏性和 DIP5 杂合子的低敏性。本文报告了 dretamycin 的生产、分离和结构解析。
