Johann Wolfgang Goethe-Universitat Frankfurt Am Main

Johann Wolfgang Goethe-Universitat

Helge B Bode

Florian Fleischhacker

Claus-Peter Niesert

Kenan Bozhüyük

Kenan Bozhueyuek

Annabell Linck

The present invention pertains to a system for the assembly and modification of non-ribosomal peptide synthases (NRPS). The system uses novel well defined building blocks (units) comprising condensation subdomains. This strategy allows for the efficient combination of assembly units referred to as eXchange Units (XU2.0) independent on their natural occurring specificity for the subsequent NRPS adenylation domain. The system of the invention allows for the easy assembly of NRPS having any amino acid sequence of choice, without any restrictions due to natural occurring NRPS units. The system also allows the exchange of natural NRPS building blocks with the inventive XU2.0 leading to the production of modified peptides. The invention provides the system, their individual exchange units, nucleic acids encoding these units, as well as methods and uses thereof.

System for the assembly and modification of non-ribosomal peptide synthases

The present invention pertains to a novel architecture of non-ribosomal peptide synthases (NRPS). The invention provides artificial NRPS wherein the naturally occurring terminal condensation or thioesterase-domain is replaced by internal condensation or dual condensation/epimerization domains. Moreover, the present invention enables the portability of terminal condensation domains to unrelated NRPS in respect of peptide release of linear peptides. The replacement results in a product independent release of the synthesized product and therefore enables the rational design of NRPS. The invention provides the new NRPS, nucleic acids encoding them, methods for artificial NRPS generation, and methods for producing non-ribosomal peptides.

Artificial non-ribosomal peptide synthases and their use

The present invention concerns a novel method for the modification and/or custom-made design of artificial non-ribosomal peptide synthetases (NRPSs) from naturally available NRPSs. The artificial NRPSs are of predetermined length and amino acid composition and sequence. Via fusion of well-defined NRPS units (so-called 'exchange units') in a certain manner, using a specific sequence motif in the linker areas it is possible to construct artificial and/or modified NRPS assembly lines, which have the ability of synthesizing peptides of a desired structure.

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Oberursel, Germany

Helge B Bode