Characterization and Crystal Structure of a Nonheme Diiron Monooxygenase Involved in Platensimycin and Platencin Biosynthesis

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dc.citation.firstpage12406en_US
dc.citation.issueNumber31en_US
dc.citation.journalTitleJournal of the American Chemical Societyen_US
dc.citation.lastpage12412en_US
dc.citation.volumeNumber141en_US
dc.contributor.authorDong, Liao-Binen_US
dc.contributor.authorLiu, Yu-Chenen_US
dc.contributor.authorCepeda, Alexis J.en_US
dc.contributor.authorKalkreuter, Edwarden_US
dc.contributor.authorDeng, Ming-Rongen_US
dc.contributor.authorRudolf, Jeffrey D.en_US
dc.contributor.authorChang, Changsooen_US
dc.contributor.authorJoachimiak, Andrzejen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.contributor.authorShen, Benen_US
dc.date.accessioned2019-11-14T17:52:26Zen_US
dc.date.available2019-11-14T17:52:26Zen_US
dc.date.issued2019en_US
dc.description.abstractNonheme diiron monooxygenases make up a rapidly growing family of oxygenases that are rarely identified in secondary metabolism. Herein, we report the in vivo, in vitro, and structural characterizations of a nonheme diiron monooxygenase, PtmU3, that installs a C-5 β-hydroxyl group in the unified biosynthesis of platensimycin and platencin, two highly functionalized diterpenoids that act as potent and selective inhibitors of bacterial and mammalian fatty acid synthases. This hydroxylation sets the stage for the subsequent A-ring cleavage step key to the unique diterpene-derived scaffolds of platensimycin and platencin. PtmU3 adopts an unprecedented triosephosphate isomerase (TIM) barrel structural fold for this class of enzymes and possesses a noncanonical diiron active site architecture with a saturated six-coordinate iron center lacking a μ-oxo bridge. This study reveals the first member of a previously unidentified superfamily of TIM-barrel-fold enzymes for metal-dependent dioxygen activation, with the majority predicted to act on CoA-linked substrates, thus expanding our knowledge of nature’s repertoire of nonheme diiron monooxygenases and TIM-barrel-fold enzymes.en_US
dc.identifier.citationDong, Liao-Bin, Liu, Yu-Chen, Cepeda, Alexis J., et al.. "Characterization and Crystal Structure of a Nonheme Diiron Monooxygenase Involved in Platensimycin and Platencin Biosynthesis." <i>Journal of the American Chemical Society,</i> 141, no. 31 (2019) American Chemical Society: 12406-12412. https://doi.org/10.1021/jacs.9b06183.en_US
dc.identifier.digitalnihms-1049820en_US
dc.identifier.doihttps://doi.org/10.1021/jacs.9b06183en_US
dc.identifier.urihttps://hdl.handle.net/1911/107686en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society.en_US
dc.titleCharacterization and Crystal Structure of a Nonheme Diiron Monooxygenase Involved in Platensimycin and Platencin Biosynthesisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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