DELTA-L-(ALPHA-AMINODIPOYL)-L-CYSTEINYL-D-VALINE SYNTHETASE - THE ORDER OF PEPTIDE-BOND FORMATION AND TIMING OF THE EPIMERIZATION REACTION

delta-L-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase cat alyses the formation of the common precursor tripeptide of both the pe nicillin and cephalosporin antibiotics from the L-enantiomers of its c onstituent amino acids. Replacement of cysteine with L-O-methylserine in preparative-scale incubations led to the isolation of both L-O-meth ylserinyl-L-valine and L-O-methylserinyl-D-valine dipeptides. The dipe ptides were characterized with the aid of authentic synthetic standard s by both H-1 NMR and electrospray ionization MS. A revised mechanism for ACV biosynthesis involving formation of the cysteinyl-valiae pepti de bond before the epimerisation of valine and subsequent condensation with the delta-carboxyl of L-alpha-aminoadipate is therefore proposed .