Discovery, isolation, and structure elucidation of dretamycin

J Nat Prod. 2014 Jun 27;77(6):1280-6. doi: 10.1021/np401019t. Epub 2014 Jun 16.

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.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Biological Products / chemistry
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology
  • Candida albicans / drug effects
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyrroles / chemistry
  • Pyrroles / isolation & purification*
  • Pyrroles / pharmacology
  • Streptomyces / chemistry*

Substances

  • Antifungal Agents
  • Biological Products
  • DRE2 protein, C albicans
  • Fungal Proteins
  • Iron-Sulfur Proteins
  • Pyrroles
  • dretamycin