delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: the order of peptide bond formation and timing of the epimerisation reaction.
delta-L-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase catalyses the formation of the common precursor tripeptide of both the penicillin and cephalosporin antibiotics from the L-enantiomers of its constituent amino acids. Replacement of cysteine with L-O-methylserine in preparative-scale incubations led to the isolation of both L-O-methylserinyl-L-valine and L-O-methylserinyl-D-valine dipeptides. The dipeptides were characterized with the aid of authentic synthetic standards by both 1H NMR and electrospray ionization MS. A revised mechanism for ACV biosynthesis involving formation of the cysteinyl-valine peptide bond before the epimerisation of valine and subsequent condensation with the delta-carboxyl of L-alpha-aminoadipate is therefore proposed.
Shiau
C Y
CY
Dyson Perrins Laboratory, Oxford Centre for Molecular Sciences, UK.
Baldwin
J E
JE
Byford
M F
MF
Sobey
W J
WJ
Schofield
C J
CJ
D000595:Amino Acid Sequence; D004151:Dipeptides / Q000096:biosynthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000031:analogs & derivatives; D013237:Stereoisomerism; D014633:Valine / Q000031:analogs & derivatives
D004151:Dipeptides; D012694:Serine; D010453:Peptide Synthases; C095368:alpha-aminoadipyl-cysteinyl-valine synthetase; D014633:Valine