Penicillin - Biosynthesis

Biosynthesis

Overall, there are three main and important steps to the biosynthesis of penicillin G (benzylpenicillin).

  • The first step is the condensation of three amino acids — -α-aminoadipic acid, -cysteine, -valine into a tripeptide. Before condensing into the tripeptide, the amino acid -valine must undergo epimerization to become -valine. The condensed tripeptide is named δ-(-α-aminoadipyl)--cysteine--valine (ACV). The condensation reaction and epimerization are both catalyzed by the enzyme δ-(-α-aminoadipyl)--cysteine--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. Isopenicillin N is a very weak intermediate, because it does not show strong antibiotic activity.
  • 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.

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