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

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dc.citation.firstpage12406
dc.citation.issueNumber31
dc.citation.journalTitleJournal of the American Chemical Society
dc.citation.lastpage12412
dc.citation.volumeNumber141
dc.contributor.authorDong, Liao-Bin
dc.contributor.authorLiu, Yu-Chen
dc.contributor.authorCepeda, Alexis J.
dc.contributor.authorKalkreuter, Edward
dc.contributor.authorDeng, Ming-Rong
dc.contributor.authorRudolf, Jeffrey D.
dc.contributor.authorChang, Changsoo
dc.contributor.authorJoachimiak, Andrzej
dc.contributor.authorPhillips, George N.Jr.
dc.contributor.authorShen, Ben
dc.date.accessioned2019-11-14T17:52:26Z
dc.date.available2019-11-14T17:52:26Z
dc.date.issued2019
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.
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.
dc.identifier.digitalnihms-1049820
dc.identifier.doihttps://doi.org/10.1021/jacs.9b06183
dc.identifier.urihttps://hdl.handle.net/1911/107686
dc.language.isoeng
dc.publisherAmerican Chemical Society
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.
dc.titleCharacterization and Crystal Structure of a Nonheme Diiron Monooxygenase Involved in Platensimycin and Platencin Biosynthesis
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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