TY  - INPR
A1  - Bozhüyük, Kenan A. J.
A1  - Präve, Leonard
A1  - Kegler, Carsten
A1  - Kaiser, Sebastian
A1  - Shi, Yan-Ni
A1  - Kuttenlochner, Wolfgang
A1  - Schenk, Leonie
A1  - Groll, Michael
A1  - Hochberg, Georg K. A.
A1  - Bode, Helge B.
T1  - Evolution inspired engineering of megasynthetases
T2  - bioRxiv
N2  - Several clinically used drugs are derived from microorganisms that often produce them via non-ribosomal peptide synthetases (NRPS), giant megasynthases that activate and connect individual amino acids in an assembly line fashion. Since NRPS are not restricted to the incorporation of the 20 proteinogenic amino acids, their efficient manipulation would allow the biotechnological generation of several different peptides including linear, cyclic and further modified derivatives. Here we describe a detailed phylogenetic analysis of several bacterial NRPS that led to the identification of a new recombination breakpoint within the thiolation (T) domain important in natural NRPS evolution. From this an evolutionary-inspired eXchange Unit between T domains (XUT) approach was developed, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as was shown for the specific production of a proteasome inhibitor, designed and assembled from five different NRPS fragments.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75702
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-757026
IS  - 2022.12.02.518901 Version 1
ER  -