Synthetic zippers as an enabling tool for engineering of non-ribosomal peptide synthetases

  • Non-ribosomal peptide synthetases (NRPSs) are the origin of a wide range of natural products, including many clinically used drugs. Engineering of these often giant biosynthetic machineries to produce novel non-ribosomal peptides (NRPs) at high titre is an ongoing challenge. Here we describe a strategy to functionally combine NRPS fragments of Gram-negative and -positive origin, synthesising novel peptides at titres up to 290 mg l-1. Extending from the recently introduced definition of eXchange Units (XUs), we inserted synthetic zippers (SZs) to split single protein NRPSs into up to three independently expressed and translated polypeptide chains. These synthetic type of NRPS (type S) enables easier access to engineering, overcomes cloning limitations, and provides a simple and rapid approach to building peptide libraries via the combination of different NRPS subunits.

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Author:Kenan A. J. BozhüyükORCiDGND, Jonas WatzelORCiDGND, Nadya AbboodORCiD, Helge Björn BodeORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2020/05/06
Date of first Publication:2020/05/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/07/25
Page Number:22
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International