The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes
D-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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Nature chemical biology - 16(2020), 9 vom: 29. Sept., Seite 1013-1018 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sikandar, Asfandyar [VerfasserIn] |
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| Links: |
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| Themen: |
1393-68-6 |
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| Anmerkungen: |
Date Completed 13.11.2020 Date Revised 16.07.2022 published: Print-Electronic ErratumIn: Nat Chem Biol. 2020 Jul 15;:. - PMID 32669684 Citation Status MEDLINE |
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| doi: |
10.1038/s41589-020-0569-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311795501 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a ErratumIn: Nat Chem Biol. 2020 Jul 15;:. - PMID 32669684 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a D-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 | ||
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Adam, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Santos-Aberturas, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Horbal, Liliya |e verfasserin |4 aut | |
| 700 | 1 | |a Luzhetskyy, Andriy |e verfasserin |4 aut | |
| 700 | 1 | |a Truman, Andrew W |e verfasserin |4 aut | |
| 700 | 1 | |a Kalinina, Olga V |e verfasserin |4 aut | |
| 700 | 1 | |a Koehnke, Jesko |e verfasserin |4 aut | |
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