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Isopenicillin N synthase (IPNS) is a non-heme iron-dependent enzyme belonging to the oxidoreductase family. This enzyme catalyzes the formation of isopenicillin N from δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV). :''N''-()-L-cysteinyl-D-valine + O2 isopenicillin N + 2 H2O This reaction is a key step in the biosynthesis of penicillin and cephalosporin antibiotics. The active sites of most isopenicillin N synthases contain an iron ion. This enzyme is also called isopenicillin N synthetase. == Mechanism == A Fe(II) metal ion in the active site of the enzyme is coordinated by at least two histidine residues, an aspartate residue, a glutamine residue, and two water molecules in the absence of a bound substrate.〔 Just two histidine residues and one aspartic acid residue are entirely conserved. Therefore, it is highly significant that these two histidine residues, His214 and His270, and one aspartic acid residue, Asp216, are precisely the ones essential for activity. When ACV binds the active site, Gln330 and one water molecule are replaced by the ACV thiolate.〔 The linear tripeptide δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV) must first be assembled from its component amino acids by N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase (ACV synthase). This allows for the binding of the substrate ACV to the deprotonated thiol group of the cysteine residue. This ligation of the thiolate to the iron center anchors the ACV within the active site.〔 The ligation of ACV results in a reduction of the FeI/FeII redox potential. This allows dioxygen to bind, which changes the oxidation state, initiating the reaction cycle.〔 An intramolecular hydrogen transfer takes place from C-3 of the cysteine residue, taking the iron back to the +II state. A thioaldehyde and a hydroperoxy ligand are produced in this process. The hydroperoxy ligand deprotonates the amide which then closes the β-lactam ring by a nucleophilic attack at the thioaldehyde carbon.〔 This causes the hydrogen atom at the C-3 of the valine residue to come closer to the iron(IV) oxo ligand which is highly electrophilic. A second hydrogen transfer occurs, most likely producing an isopropyl radical which closes the thiazolidine ring by attacking the thiolate sulfur atom.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Isopenicillin N synthase」の詳細全文を読む スポンサード リンク
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