Assay for the Enantiomeric Analysis of [2H1]-Fluoroacetic Acid: Insight into the Stereochemical Course of Fluorination during Fluorometabolite Biosynthesis in Streptomyces cattleya

David O'Hagan, RJM Goss, A Meddour, J Courtieu

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37 Citations (Scopus)

Abstract

A sensitive method for the configurational analysis of (R)- and (S)-[H-2(1)]-fluoroacetate has been developed using H-2{H-1}-NMR in a chiral liquid crystalline solvent. This has enabled biosynthetic experiments to be conducted which reveal stereochemical details on biological fluorination occurring during the biosynthesis of fluoroacetate and 4-fluorothreonine in the bacterium Streptomyces cattleya. In particular, feeding experiments to S. cattleya with isotopically labeled (1R, 2R)- and (1S, 2R)-[1-H-2(1)]-glycerol 3d and 3e and [2,3-H-2(4)]-Succinate 4a gave rise to samples of enantiomerically enriched [2-H-2(1)]-fluoroacetates 1a. The predominant enantiomer resulting from each experiment suggests that the stereochemical course of biological fluorination takes place with an overall retention of configuration between a glycolytic intermediate and fluoroacetate 1. Consequently, this outcome suggests that the stereochemical course of the recently identified fluorinase enzyme which mediates a reaction between fluoride ion and S-adenosyl-L-methionine (SAM), occurs with an inversion of configuration.

Original languageEnglish
Pages (from-to)379-387
Number of pages9
JournalJournal of the American Chemical Society
Volume125
Issue number2
DOIs
Publication statusPublished - 15 Jan 2003

Keywords

  • NATURAL-PRODUCTS
  • DEUTERIUM NMR
  • FLUOROACETATE
  • 4-FLUOROTHREONINE
  • GLYCEROL
  • PATHWAY
  • AGENTS

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