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dc.contributor.authorAdam, Sebastian
dc.contributor.authorFranz, Laura
dc.contributor.authorMilhim, Mohammed
dc.contributor.authorBernhardt, Rita
dc.contributor.authorKalinina, Olga V
dc.contributor.authorKoehnke, Jesko
dc.date.accessioned2021-07-23T09:02:37Z
dc.date.available2021-07-23T09:02:37Z
dc.date.issued2020-11-28
dc.identifier.citationJ Am Chem Soc. 2020 Dec 9;142(49):20560-20565. doi: 10.1021/jacs.0c10361. Epub 2020 Nov 28.en_US
dc.identifier.pmid33249843
dc.identifier.doi10.1021/jacs.0c10361
dc.identifier.urihttp://hdl.handle.net/10033/622954
dc.description.abstractBottromycins are ribosomally synthesized and post-translationally modified peptide natural product antibiotics that are effective against high-priority human pathogens such as methicillin-resistant Staphylococcus aureus. The total synthesis of bottromycins involves at least 17 steps, with a poor overall yield. Here, we report the characterization of the cytochrome P450 enzyme BotCYP from a bottromycin biosynthetic gene cluster. We determined the structure of a close BotCYP homolog and used our data to conduct the first large-scale survey of P450 enzymes associated with RiPP biosynthetic gene clusters. We demonstrate that BotCYP converts a C-terminal thiazoline to a thiazole via an oxidative decarboxylation reaction and provides stereochemical resolution for the pathway. Our data enable the two-pot in vitro production of the bottromycin core scaffold and may allow the rapid generation of bottromycin analogues for compound development.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleCharacterization of the Stereoselective P450 Enzyme BotCYP Enables the Biosynthesis of the Bottromycin Core Scaffold.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.eissn1520-5126
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalJournal of the American Chemical Societyen_US
dc.source.volume142
dc.source.issue49
dc.source.beginpage20560
dc.source.endpage20565
dc.source.journaltitleJournal of the American Chemical Society
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International