Seite - (000055) - in Biomedical Chemistry: Current Trends and Developments

condensation of three amino acids catalysed by ACV synthase. ACV is then processed by isopenicillin-N synthase, an enzyme of the oxyreductase family, with the following mechanistic steps (Scheme 1.1.40): 1. Attachment of the cysteine thiol moiety by displacing a water ligand 2. Oxidation of Fe(II) to Fe(III) by molecular oxygen, creating a radical species 3. Intramolecular hydrogen transfer, oxidation of the thiol to thioaldehyde (extremely reactive due higher dipole moment than that of an aldehyde) and reduction of Fe(III) to Fe(II) 4. Amide deprotonation by the hydroperoxide ligand and nucleophilic addition of the nitrogen to the thiol with oxidation of Fe(II) to Fe(IV). This transformation results in the lactam ring formation 5. Radical formation by hydrogen abstraction by the oxide (turns into an hydroxide ligand) with reduction of Fe(IV) to Fe(III) 6. Radical attack of the sulfur atom, closing the thiazolidine ring and reducing Fe(III) to Fe(II) 7. Displacement of the sulfur by water to restore the enzyme active site and release isopenicillin-N.