The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes.
Sikandar et al.pdf
extended data files (*.tif) 1 ...
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Truman, Andrew W
Kalinina, Olga V
MetadataShow full item record
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.
CitationNat Chem Biol. 2020 Jul 15;:]. Nat Chem Biol. 2020;16(9):1013-1018. doi:10.1038/s41589-020-0569-y.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
JournalNature chemical biology
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- The genomic landscape of ribosomal peptides containing thiazole and oxazole heterocycles.
- Authors: Cox CL, Doroghazi JR, Mitchell DA
- Issue date: 2015 Oct 13
- Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP.
- Authors: Mann G, Huo L, Adam S, Nardone B, Vendome J, Westwood NJ, Müller R, Koehnke J
- Issue date: 2016 Dec 2
- Peptide Epimerization Machineries Found in Microorganisms.
- Authors: Ogasawara Y, Dairi T
- Issue date: 2018
- Author Correction: The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes.
- Authors: Sikandar A, Franz L, Adam S, Santos-Aberturas J, Horbal L, Luzhetskyy A, Truman AW, Kalinina OV, Koehnke J
- Issue date: 2020 Sep
- Macroamidine Formation in Bottromycins Is Catalyzed by a Divergent YcaO Enzyme.
- Authors: Franz L, Adam S, Santos-Aberturas J, Truman AW, Koehnke J
- Issue date: 2017 Dec 20