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IPNS converts the tripeptide \u03b4\u2010(<jats:sc>l<\/jats:sc>\u2010\u03b1\u2010aminoadipoyl)\u2010<jats:sc>l<\/jats:sc>\u2010cysteinyl\u2010<jats:sc>d<\/jats:sc>\u2010valine (ACV) to isopenicillin N while reducing molecular oxygen to water. The substrate analogue \u03b4\u2010(<jats:sc>l<\/jats:sc>\u2010\u03b1\u2010aminoadipoyl)\u2010<jats:sc>l<\/jats:sc>\u2010cysteinyl\u2010<jats:italic>O<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010threonine (ACmT) is not turned over by IPNS. Epimeric \u03b4\u2010(<jats:sc>l<\/jats:sc>\u2010\u03b1\u2010aminoadipoyl)\u2010<jats:sc>l<\/jats:sc>\u2010cysteinyl\u2010<jats:italic>O<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010<jats:italic>allo<\/jats:italic>\u2010threonine (ACm<jats:italic>a<\/jats:italic>T) is converted to a bioactive penam product. ACmT and ACm<jats:italic>a<\/jats:italic>T differ from each other only in the stereochemistry at the \u03b2\u2010carbon atom of their third residue. These substrates both contain a methyl ether in place of the isopropyl group of ACV. We report an X\u2010ray crystal structure for the anaerobic IPNS:Fe(II):ACmT complex. 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