Ali, Ataurehman ; Happel, Dominic ; Habermann, Jan ; Schoenfeld, Katrin ; Macarrón Palacios, Arturo ; Bitsch, Sebastian ; Englert, Simon ; Schneider, Hendrik ; Avrutina, Olga ; Fabritz, Sebastian ; Kolmar, Harald (2022)
Sactipeptide Engineering by Probing the Substrate Tolerance of a Thioether‐Bond‐Forming Sactisynthase.
In: Angewandte Chemie International Edition, 2022, 61 (45)
doi: 10.26083/tuprints-00022904
Artikel, Zweitveröffentlichung, Verlagsversion
Kurzbeschreibung (Abstract)
Sactipeptides are ribosomally synthesized peptides containing a unique sulfur to α‐carbon crosslink. Catalyzed by sactisynthases, this thioether pattern endows sactipeptides with enhanced structural, thermal, and proteolytic stability, which makes them attractive scaffolds for the development of novel biotherapeutics. Herein, we report the in‐depth study on the substrate tolerance of the sactisynthase AlbA to catalyze the formation of thioether bridges in sactipeptides. We identified a possible modification site within the sactipeptide subtilosin A allowing for peptide engineering without compromising formation of thioether bridges. A panel of natural and hybrid sactipeptides was produced to study the AlbA‐mediated formation of thioether bridges, which were identified mass‐spectrometrically. In a proof‐of‐principle study, we re‐engineered subtilosin A to a thioether‐bridged, specific streptavidin targeting peptide, opening the door for the functional engineering of sactipeptides.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Ali, Ataurehman ; Happel, Dominic ; Habermann, Jan ; Schoenfeld, Katrin ; Macarrón Palacios, Arturo ; Bitsch, Sebastian ; Englert, Simon ; Schneider, Hendrik ; Avrutina, Olga ; Fabritz, Sebastian ; Kolmar, Harald |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Sactipeptide Engineering by Probing the Substrate Tolerance of a Thioether‐Bond‐Forming Sactisynthase |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2022 |
| Verlag: | Wiley-VCH |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Angewandte Chemie International Edition |
| Jahrgang/Volume einer Zeitschrift: | 61 |
| (Heft-)Nummer: | 45 |
| Kollation: | 8 Seiten |
| DOI: | 10.26083/tuprints-00022904 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/22904 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Sactipeptides are ribosomally synthesized peptides containing a unique sulfur to α‐carbon crosslink. Catalyzed by sactisynthases, this thioether pattern endows sactipeptides with enhanced structural, thermal, and proteolytic stability, which makes them attractive scaffolds for the development of novel biotherapeutics. Herein, we report the in‐depth study on the substrate tolerance of the sactisynthase AlbA to catalyze the formation of thioether bridges in sactipeptides. We identified a possible modification site within the sactipeptide subtilosin A allowing for peptide engineering without compromising formation of thioether bridges. A panel of natural and hybrid sactipeptides was produced to study the AlbA‐mediated formation of thioether bridges, which were identified mass‐spectrometrically. In a proof‐of‐principle study, we re‐engineered subtilosin A to a thioether‐bridged, specific streptavidin targeting peptide, opening the door for the functional engineering of sactipeptides. |
| Freie Schlagworte: | Bioengineering, Miniproteins, RiPPs, Sactipeptides, Sactisynthases |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-229041 |
| Zusätzliche Informationen: | International Version |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | Interdisziplinäre Forschungsprojekte Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie |
| Hinterlegungsdatum: | 23 Dez 2022 14:16 |
| Letzte Änderung: | 28 Dez 2022 07:17 |
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| Zugehörige Links: | |
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