Incorporation of 3H from delta-(L-alpha-amino (4,5-3H)adipyl)-L-cysteinyl-D-(4,4-3H)valine into isopenicillin N.
1. delta-(L-alpha-Amino[4,5-3H]adipyl)-L-cysteinyl-D-[4,4-3H]valine has been synthesized from its constituent amino acids, the L-alpha-amino[4,5-3H]adipic acid being obtained by reduction with 3H2 of methyl 5-acetamido-5,5-diethoxycarbonylpent-2-enoate and subsequent decarboxylation and hydrolysis. 2. In a cell-free system prepared by lysis of protoplasts of Cephalosporium acremonium 3H was incorporated from the doubly labelled tripeptide into a compound that behaved like penicillin N or isopenicillin N. The relative specific radioactivities of the alpha-aminoadipyl and penicillamine moieties of the penicillin were the same (within experimental error) as those of the alpha-aminoadipic acid and valine residues respectively of the tripeptide. 3. The behaviour of the labelled alpha-aminoadipic acid from the penicillin to the L-amino acid oxidase of Crotalus adamanteus venom showed that it was mainly L-alpha-aminoadipic acid. 4. The results are consistent with the hypothesis that the carbon skeleton of the LLD-tripeptide is incorporated intact into the penicillin molecule and that the first product is isopenicillin N.
D015074:2-Aminoadipic Acid / Q000378:metabolism; D000164:Acremonium / Q000378:metabolism; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D007536:Isomerism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D010406:Penicillins / Q000096:biosynthesis*; D014316:Tritium
D009842:Oligopeptides; D010406:Penicillins; D014316:Tritium; D015074:2-Aminoadipic Acid; D000594:Amino Acid Oxidoreductases; C006414:penicillin N