Assay for the enantiomeric analysis of [2H1]-fluoroacetic acid: insight into the stereochemical course of fluorination during fluorometabolite biosynthesis in streptomyces cattleya.
A sensitive method for the configurational analysis of (R)- and (S)-[2H1]-fluoroacetate has been developed using 2H[1H]-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)-[1-2H1]-glycerol 3d and 3e and [2,3-2H(4)]-succinate 4a gave rise to samples of enantiomerically enriched [2-2H1]-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.
O'Hagan
David
D
School of Chemistry, University of St Andrews, Centre of Biomolecular Sciences, North Haugh, United Kingdom, KY15 9EA.
Goss
Rebecca J M
RJ
Meddour
Abdelkrim
A
Courtieu
Jacques
J
D003903:Deuterium; D005463:Fluoroacetates / Q000737:chemistry / Q000378:metabolism*; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*; D019802:Succinic Acid / Q000737:chemistry / Q000378:metabolism; D013912:Threonine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry
D005463:Fluoroacetates; C048271:4-fluorothreonine; D013912:Threonine; D012436:S-Adenosylmethionine; D019802:Succinic Acid; C014815:fluoroacetic acid; D003903:Deuterium; D005990:Glycerol