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dc.contributor.authorNg, Tai L.
dc.contributor.authorRohac, Roman
dc.contributor.authorMitchell, Andrew J.
dc.contributor.authorBoal, Amie K.
dc.contributor.authorBalskus, Emily P.
dc.contributor.authorBalskus, Emily
dc.date.accessioned2020-12-10T16:26:37Z
dc.date.issued2019-02
dc.identifier.citationNg, T.L., Rohac, R., Mitchell, A.J. et al. An N-nitrosating metalloenzyme constructs the pharmacophore of streptozotocin. Nature 566, 94–99 (2019). https://doi.org/10.1038/s41586-019-0894-zen_US
dc.identifier.issn0028-0836en_US
dc.identifier.issn1476-4687en_US
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37366569*
dc.description.abstractN-nitroso-containing small molecules, such as the bacterial natural product streptozotocin, are prominent carcinogens as well as important cancer chemotherapeutics. Despite this functional group’s significant impact on human health, dedicated enzymes involved in N-nitroso assembly have not been identified. Here, we describe a metalloenzyme from streptozotocin biosynthesis (SznF) that catalyzes an unprecedented oxidative rearrangement of the guanidine group of Nw-methyl-L-arginine to generate an N-nitrosourea product. Structural characterization and mutagenesis of SznF uncovered two separate active sites that promote distinct steps in this transformation using different iron-containing metallocofactors. The discovery of this biosynthetic reaction, which has little precedent in enzymology or organic synthesis, expands the catalytic capabilities of non-heme iron-dependent enzymes to include N–N bond formation. We find biosynthetic gene clusters encoding SznF homologs are widely distributed among bacteria, including environmental organisms, plant symbionts, and human pathogens, suggesting an unexpectedly diverse and uncharacterized microbial reservoir of bioactive N-nitroso metabolites.en_US
dc.description.sponsorshipChemistry and Chemical Biologyen_US
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relationNatureen_US
dash.licenseMETA_ONLY
dc.subjectMultidisciplinaryen_US
dc.titleAn N-nitrosating metalloenzyme constructs the pharmacophore of streptozotocinen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNatureen_US
dash.depositing.authorBalskus, Emily
dash.waiver2018-11-28
dc.date.available2020-12-10T16:26:37Z
dash.affiliation.otherFaculty of Arts & Sciencesen_US
dc.identifier.doi10.1038/s41586-019-0894-z
dc.source.journalNature
dash.source.volume566;7742
dash.source.page94-99
dash.contributor.affiliatedBalskus, Emily


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