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  3. Two iron(II), $\alpha$-ketoglutarate-dependent enzymes encoded by the PPZ gene cluster of Metarhizium majus enable production of 8-hydroxyperamine

Two iron(II), $\alpha$-ketoglutarate-dependent enzymes encoded by the PPZ gene cluster of Metarhizium majus enable production of 8-hydroxyperamine

TitleTwo iron(II), $\alpha$-ketoglutarate-dependent enzymes encoded by the PPZ gene cluster of Metarhizium majus enable production of 8-hydroxyperamine
Publication TypeJournal Article
Year of Publication2024
AuthorsRothchild, KW, Hagar, M, Berry, D, Ryan, KS
JournalJ. Am. Chem. Soc.
Volume146
Pagination10263–10267
Abstract

Entomopathogenic fungus Metarhizium majus contains the nine-gene PPZ cluster, with ppzA, encoding a peramine-producing nonribosomal peptide synthetase, as the central component. In this work, the roles of two $\alpha$-ketoglutarate, iron-dependent oxygenases encoded by the PPZ genes ppzC and ppzD were elucidated. PpzD was found to produce both trans-4-hydroxy-l-proline and trans-3-hydroxy-l-proline in a 13.1:1 ratio, yielding a key precursor for peramine biosynthesis. PpzC was found to act directly on peramine, yielding the novel analogue 8-hydroxyperamine.