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. Efficient engineering of these often giant biosynthetic machineries to produce novel non-ribosomal peptides (NRPs) is an ongoing challenge. Here we describe a cloning and co-expression strategy to functionally combine NRPS fragments of Gram-negative and -positive origin, synthesising novel peptides at titres up to 220 mg L−1. Extending from the recently introduced definition of eXchange Units (XUs), we inserted synthetic zippers (SZs) to split single protein NRPSs into 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.
Author:Kenan A. J. BozhüyükORCiDGND, Jonas WatzelORCiDGND, Nadya AbboodORCiD, Helge Björn BodeORCiDGND
Parent Title (German):Angewandte Chemie
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2021/05/20
Date of first Publication:2021/05/20
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/04/05
Tag:artificial docking domains; biosynthesis; engineering; non-ribosomal peptide syntheses; novel natural products
Page Number:8
First Page:17531
Last Page:17538
This work was supported by the LOEWE research cluster MegaSyn, the LOEWE center TBG, both funded by the state of Hesse and an ERC advanced grant (grant agreement number 835108). Open access funding enabled and organized by Projekt DEAL.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0