Chaxamycins A-D, Bioactive Ansamycins From a Hyper-Arid Desert Streptomyces Sp

J Nat Prod. 2011 Jun 24;74(6):1491-9. doi: 10.1021/np200320u. Epub 2011 May 9.

Abstract

Streptomyces sp. strain C34, isolated from soil collected in the Chilean hyper-arid Atacama Desert, was cultured on different media, resulting in the isolation and identification of four new ansamycin-type polyketides. The organism was selected for chemical investigation on the basis of a genome-mining PCR-based experiment targeting the gene encoding rifamycin-specific 3-amino-5-hydroxybenzoic acid synthetase (AHBA). The isolated compounds were structurally characterized using NMR and MS techniques and named chaxamycins A-D (1-4). Compounds 1-4 were tested for their antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 and for their ability to inhibit the intrinsic ATPase activity of the heat shock protein 90 (Hsp90). Chaxamycin D (4), which showed a selective antibacterial activity against S. aureus ATCC 25923, was tested further against a panel of MRSA clinical isolates. In a virtual screening experiment, chaxamycins A-D (1-4) have also been docked into the ATP-binding pocket in the N-terminal domain of the Hsp90, and the observed interactions are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / drug effects
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / pharmacology
  • Escherichia coli / drug effects
  • HSP90 Heat-Shock Proteins / drug effects
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism
  • Lactams, Macrocyclic / chemistry
  • Lactams, Macrocyclic / isolation & purification*
  • Lactams, Macrocyclic / pharmacology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Molecular Structure
  • Streptomyces / chemistry*

Substances

  • Anti-Bacterial Agents
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Adenosine Triphosphatases
  • 3-amino-5-hydroxybenzoic acid synthase
  • Hydro-Lyases