Characterization and application of the Fe(II) and α-ketoglutarate dependent hydroxylase FrbJ

Chem Commun (Camb). 2011 Sep 28;47(36):10025-7. doi: 10.1039/c1cc13597j. Epub 2011 Aug 10.

Abstract

The Fe(II) and α-ketoglutarate-dependent hydroxylase FrbJ was previously demonstrated to utilize FR-900098 synthesizing a second phosphonate FR-33289. Here we assessed its ability to hydroxylate other possible substrates, generating a library of potential antimalarial compounds. Through a series of bioassays and in vitro experiments, we identified two new antimalarials.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antimalarials / chemistry*
  • Antimalarials / metabolism
  • Antimalarials / pharmacology
  • Bacterial Proteins / metabolism*
  • Ferrous Compounds / chemistry*
  • Fosfomycin / analogs & derivatives
  • Fosfomycin / biosynthesis
  • Fosfomycin / chemistry
  • Fosfomycin / pharmacology
  • Ketoglutaric Acids / chemistry*
  • Mixed Function Oxygenases / metabolism*
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / enzymology
  • Streptomyces / enzymology

Substances

  • Antimalarials
  • Bacterial Proteins
  • Ferrous Compounds
  • Ketoglutaric Acids
  • Fosfomycin
  • fosmidomycin
  • 3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid
  • FR 33289
  • Mixed Function Oxygenases