Non-ribosomal protein synthesis peptides
DKFZ Deutsches Krebsforschungszentrum
Non-ribosomal peptides (NRPs) are secondary metabolites produced by microorganisms, e.g. bacteria and fungi. Unlike ribosomal protein biosynthesis, non-ribosomal protein synthesis (NRPS) does not require mRNA to direct the sequence of monomers incorporated into the growing peptide chain, and can therefore introduce proteinogenic as well as non-proteinogenic amino acids. In NRPS, the peptide sequence is controlled by the sequence of amino acid modules within
the enzyme, non-ribosomal peptide synthetase (NRPSase), whereby each module is responsible for the specific incorporation of one amino acid, respectively.
NRPSases are known to have a modular architecture, with single modules being specific for a single amino acid. The separate modules can be connected either covalently or by protein-protein interactions via so called communication domains to form large multimodule-proteins. Every NRPS module consists of three domains that activate the respective amino acid (A-domain), catalyze the condensation (C-domain), and carry the resulting peptide chain (T-domain).
The presented technology provides means and methods for producing NRPS modules that are functionally connected to a NRPS pigment module, especially the indigoidine synthetase module.
The inventors were able to synthesize a variety of recombined NRPSases for the production of indigoidine-labeled mono-, di-, tri-, or oligo-peptides.
Applications and Commercial Opportunity
Non-ribosomal peptides (NRPs) are a promising source of functional molecules such as antibiotics. The technology allows for the identification, high-throughput screening and easy purification of engineered NRPs by optical measures, for example in thin layer chromatography (TLC), HPLC / FPLC, or measurement of optical densities at 600 nm.
The technology was developed by researchers of the Division of Theoretical Bioinformatics at the DKFZ and the University of Heidelberg, Germany.
The patent application “Non-ribosomal protein synthesis pigment fusion peptides” was filed October 2, 2013 at the EPO.