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Sactipeptide Engineering by Probing the Substrate Tolerance of a Thioether‐Bond‐Forming Sactisynthase

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
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Item Type: Article
Type of entry: Secondary publication
Title: Sactipeptide Engineering by Probing the Substrate Tolerance of a Thioether‐Bond‐Forming Sactisynthase
Language: English
Date: 23 December 2022
Place of Publication: Darmstadt
Year of primary publication: 2022
Publisher: Wiley-VCH
Journal or Publication Title: Angewandte Chemie International Edition
Volume of the journal: 61
Issue Number: 45
Collation: 8 Seiten
DOI: 10.26083/tuprints-00022904
Corresponding Links:
Origin: Secondary publication DeepGreen
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.

Uncontrolled Keywords: Bioengineering, Miniproteins, RiPPs, Sactipeptides, Sactisynthases
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-229041
Additional Information:

International Version

Classification DDC: 500 Science and mathematics > 540 Chemistry
500 Science and mathematics > 570 Life sciences, biology
Divisions: Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
Date Deposited: 23 Dec 2022 14:16
Last Modified: 14 Nov 2023 19:05
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/22904
PPN: 503250910
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