TY  - JOUR
A1  - Bozhüyük, Kenan A. J.
A1  - Watzel, Jonas
A1  - Abbood, Nadya
A1  - Bode, Helge Björn
T1  - Synthetic zippers as an enabling tool for engineering of non-ribosomal peptide synthetases
T2  - Angewandte Chemie
N2  - 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.
KW  - artificial docking domains
KW  - biosynthesis
KW  - engineering
KW  - non-ribosomal peptide syntheses
KW  - novel natural products
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63908
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-639088
SN  - 1521-3773
N1  - 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.
VL  - 60
IS  - 32
SP  - 17531
EP  - 17538
PB  - Wiley-VCH
CY  - Weinheim
ER  -