When was penicillin discovered?
Penicillin
The first step is the condensation of three amino acids—L-α-aminoadipic acid, L-cysteine, L-valine into a tripeptide.[58][59][60] Before condensing into the tripeptide, the amino acid L-valine must undergo epimerization to become D-valine.[61][62] The condensed tripeptide is named δ-(L-α-aminoadipyl)-L-cysteine-D-valine (ACV). The condensation reaction and epimerization are both catalyzed by the enzyme δ-(L-α-aminoadipyl)-L-cysteine-D-valine synthetase (ACVS), a nonribosomal peptide synthetase or NRPS.
The second step in the biosynthesis of penicillin G is the oxidative conversion of linear ACV into the bicyclic intermediate isopenicillin N by isopenicillin N synthase (IPNS), which is encoded by the gene pcbC.[58][59] Isopenicillin N is a very weak intermediate, because it does not show strong antibiotic activity.[61]
The final step is a transamidation by isopenicillin N N-acyltransferase, in which the α-aminoadipyl side-chain of isopenicillin N is removed and exchanged for a phenylacetyl side-chain. This reaction is encoded by the gene penDE, which is unique in the process of obtaining penicillins.[58]