METHOD OF MODIFYING PEPTIDE SYNTHETASES SUCH THAT THEY CAN N-METHYLATE THEIR SUBSTRATE AMINO ACIDS

摘要

The invention relates to a method of modifying peptide synthetases in such a manner that they can N-methylate their substrate amino acids. PPS are enzyme s that synthesize peptides in a non-ribosomal manner. PPS have a modular set-u p. Each module has an activation domain which recognizes and covalently binds t o the respective substrate amino acid. The peptide synthesis catalyzed by PPS proceeds by the condensation of the covalently bound substrate amino acids. A minor number of the known activation domains is capable of also N-methylatin g the bound substrate amino acids. The inventive method allows conversion of t he activation domains without N-methyl transferase activity to activation domai ns with N-methyl transferase activity while maintaining the original substrate specificity.