Ribosomal synthesis of dehydrobutyrine- and methyllanthionine-containing peptides

Abstract

We report here the ribosomal synthesis of methyllanthionine-containing cyclic peptides involving a site-specific incorporation of vinylglycine under the reprogrammed genetic code, followed by the isomerization of the vinylglycine to dehydrobutyrine, and the subsequent intramolecular Michael addition of a cysteine residue placed at a downstream position of the vinylglycine.

Recombinant Macrocyclic Lanthipeptides Incorporating Non-Canonical Amino Acids

“…To further explore the potential utility of this complex natural product, various efforts have been undertaken to generate variants of Nisin and other lantibiotics, 9 including the use of solid phase synthesis, 10-12 biomimetic approaches, 13 the in vitro biosynthesis of lanthionine-containing peptides 14-15 and an in vitro mutasynthetic approach. 16 …”

Encoded libraries of chemically modified peptides

“…Suga et al developed several other cyclization strategies with unnatural amino acids that might also be applied to mRNA-encoded peptide libraries in the future. Examples are the oxidative coupling of 5-hydroxytryptophan and benzylamine linked to the a-amino group of phenylalanine (Figure 3d) [32] or the Michael addition of cysteine to dehydrobutyrine (Figure 3e) [33]. In the latter reaction, the unnatural amino acid vinylglycine was incorporated and transformed by heating into dehydrobutyrine.…”

Engineering the Translation Apparatus to Incorporate Nonnatural Amino Acids

“…Impressively, this system is able to initiate translation with tRNA charged with peptides [40]. The incorporation of nonnatural amino acids by flexizymes and successive reactions between nonnatural amino acids can be further utilized as a novel way to generate cyclic peptides, which may have important physiological effects [38,[41][42][43][44][45]. In addition, the flexizyme has been further modified to increase its tRNA specificity by adding a sequence to its 3'-end [46].…”