title: Discovery, isolation, and structure elucidation of dretamycin.
abstract: 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.
authors.affiliation: Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, United States.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Wilson
authors.forename: Scott K
authors.initials: SK
authors.lastname: Smith
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Kelly
authors.forename: Prakash
authors.initials: P
authors.lastname: Masurekar
authors.forename: Deming
authors.initials: D
authors.lastname: Xu
authors.forename: Craig A
authors.initials: CA
authors.lastname: Parish
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Zink
authors.forename: Julian E
authors.initials: JE
authors.lastname: Davies
authors.forename: Terry
authors.initials: T
authors.lastname: Roemer
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; C000590591:DRE2 protein, C albicans; D005656:Fungal Proteins; D007506:Iron-Sulfur Proteins; D011758:Pyrroles; C000591071:dretamycin