FIELD: biotechnology.
SUBSTANCE: invention relates to the biotechnology. Described is a method of displaying a cyclic peptide on the surface of a bacteriophage particle, comprising the following steps: (a) providing a host cell comprising a nucleic acid sequence encoding a precursor of a cyclic peptide; a nucleic acid sequence encoding a bacteriophage particle capsid protein; a leader sequence which is recognized by the post-translational modification (PTM) system enzyme; and one or more nucleic acid sequences encoding a post-translational modification system enzyme which is a lantypeptide synthase; (b) initiating or enabling expression of said cyclic peptide precursor; (c) enzymatic dehydration of one or more amino acid residues in a precursor of a cyclic peptide; (d) forming one or more intramolecular bonds by binding said one or more dehydrated residues with cysteine or lysine, thereby forming a cyclic peptide; and (e) obtaining bacteriophage particles in said host cell, wherein said bacteriophage particles "map" said cyclic peptide on the surface, and wherein said cyclic peptide is attached to the C-end of the capsid protein of said bacteriophage particles. Invention also relates to a nucleic acid molecule which "maps" a cyclic peptide on the surface of a bacteriophage particle, where said nucleic acid encodes (a) a capsid protein of said bacteriophage particle; (b) a leader sequence which is recognized by the post-translational modification (PTM) system enzyme, and (c) a cyclic peptide precursor, wherein the nucleic acid coding the cyclic peptide precursor is located at the C-end of the capsid protein of said bacteriophage particle, and wherein said cyclic peptide precursor is able to form an intramolecular linkage by binding one or more dehydrated residues with cysteine or lysine. Described is a bacteriophage particle which "maps" on its surface a cyclic peptide obtained by said method, where said cyclic peptide is attached to the C-end of the capsid protein of said bacteriophage particle. Besides, a genetically diverse library of bacteriophage particles according to para. 11, where each of said bacteriophage particles "maps" the cyclic peptide from a genetically diverse cyclic peptide library, wherein said cyclic peptides contain an intramolecular linkage formed by binding one or more dehydrated residues with cysteine or lysine.
EFFECT: invention extends the range of phage displays.
13 cl, 5 dwg, 4 ex
Authors
Dates
2019-10-03—Published
2015-12-21—Filed