Metabolites of a blocked chloramphenicol producer

J Nat Prod. 2003 Jan;66(1):62-6. doi: 10.1021/np020306e.

Abstract

Addition of p-aminophenylalanine (4), an advanced biosynthetic precursor of the antibiotic chloramphenicol (5), to a Streptomyces venezuelae pabAB mutant (VS629) restored chloramphenicol production and led to formation of the non-chlorinated analogue corynecin II (6) and four acetanilide derivatives: p-(acetylamino)phenylalanine (7), p-(acetylamino)benzyl alcohol (13), p-(acetylamino)benzoic acid (14), and p-(acetylamino)phenol (acetaminophen, 16). Metabolite structures were deduced from NMR and MS-MS data and established by chromatographic and spectroscopic comparisons with authentic samples. Reference compound 13 was synthesized by reducing the acid chloride of 14. Shunt pathways are proposed to account for the formation of the metabolites from p-aminophenylalanine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobenzoic Acid / metabolism
  • Anti-Bacterial Agents / biosynthesis*
  • Chloramphenicol / biosynthesis*
  • Chromatography, High Pressure Liquid
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology*
  • Streptomyces / drug effects*
  • Streptomyces / enzymology*

Substances

  • Anti-Bacterial Agents
  • 4-aminophenylalanine
  • Phenylalanine
  • Chloramphenicol
  • 4-Aminobenzoic Acid