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dc.contributor.authorSikandar, Asfandyar
dc.contributor.authorFranz, Laura
dc.contributor.authorAdam, Sebastian
dc.contributor.authorSantos-Aberturas, Javier
dc.contributor.authorHorbal, Liliya
dc.contributor.authorLuzhetskyy, Andriy
dc.contributor.authorTruman, Andrew W
dc.contributor.authorKalinina, Olga V
dc.contributor.authorKoehnke, Jesko
dc.date.accessioned2020-08-31T14:13:30Z
dc.date.available2020-08-31T14:13:30Z
dc.date.issued2020-06-29
dc.identifier.citationNat Chem Biol. 2020 Jul 15;:]. Nat Chem Biol. 2020;16(9):1013-1018. doi:10.1038/s41589-020-0569-y.en_US
dc.identifier.pmid32601484
dc.identifier.doi10.1038/s41589-020-0569-y
dc.identifier.urihttp://hdl.handle.net/10033/622421
dc.description.abstractd-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of l-amino acids into their d-counterparts is rare and chemically challenging. Bottromycins are ribosomally synthesized and post-translationally modified peptides that have overcome this challenge and feature a d-aspartate (d-Asp), which was proposed to arise spontaneously during biosynthesis. We have identified the highly unusual α/β-hydrolase (ABH) fold enzyme BotH as a peptide epimerase responsible for the post-translational epimerization of l-Asp to d-Asp during bottromycin biosynthesis. The biochemical characterization of BotH combined with the structures of BotH and the BotH–substrate complex allowed us to propose a mechanism for this reaction. Bioinformatic analyses of BotH homologs show that similar ABH enzymes are found in diverse biosynthetic gene clusters. This places BotH as the founding member of a group of atypical ABH enzymes that may be able to epimerize non-Asp stereocenters across different families of secondary metabolites.en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleThe bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes.en_US
dc.typeArticleen_US
dc.identifier.eissn1552-4469
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalNature chemical biologyen_US
dc.source.volume16
dc.source.issue9
dc.source.beginpage1013
dc.source.endpage1018
dc.source.journaltitleNature chemical biology
dc.source.countryUnited States


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