Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase, the multienzyme integrating the four primary reactions in beta-lactam biosynthesis, as a model peptide synthetase.
ACV synthetase forms the tripeptide precursor of penicillins and cephalosporins from alpha-aminoadipate, cysteine, and valine. Catalytic sites for substrate carboxyl activation as adenylates, peptide bond formations, epimerization and release of the tripeptide-thioester are integrated in multifunctional enzymes of 405 to 425 kD. These have been characterized from several pro- and eukaryotic beta-lactam producers. Implications of these results for the thio-template mechanism of peptide formation are discussed, as well as the use of this multienzyme as a model system for enzymatic peptide synthesis.
Aharonowitz
Y
Y
Institut für Biochemie und Molekulare Biologie, Technische Universität Berlin, F.R.G.
Bergmeyer
J
J
Cantoral
J M
JM
Cohen
G
G
Demain
A L
AL
Fink
U
U
Kinghorn
J
J
Kleinkauf
H
H
MacCabe
A
A
Palissa
H
H
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002384:Catalysis; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D010453:Peptide Synthases; C095368:alpha-aminoadipyl-cysteinyl-valine synthetase