Association of Radical Chemistry with LanD Flavoprotein Activity for C-Terminal Macrocyclization of a Ribosomal Peptide by Formation of an Unsaturated Thioether Residue.
Angew Chem Int Ed Engl
; 62(35): e202308733, 2023 08 28.
Article
en En
| MEDLINE
| ID: mdl-37431841
ABSTRACT
LanD flavoproteins catalyze oxidative decarboxylation of the C-terminal Cys residue of a peptide to produce an enethiol. This enethiol is highly reactive and can be coupled with an upstream dehydroamino acid through Michael addition to form S-[2-aminovinyl](3-methyl)cysteine, an unsaturated thioether residue known to be characteristic of an array of C-terminally macrocyclized, ribosomally synthesized and posttranslationally modified peptides (RiPPs). Based on a two-stage bioinformatics mining of posttranslational modifications (PTMs) related to C-terminal Cys processing, we report herein that LanD activity can couple with radical S-adenosylmethionine chemistry to provide a new unsaturated thioether residue, S-[2-aminovinyl]-3-carbamoylcysteine, by conjugating the resultant enethiol with Cß of the Asn residue in the C-terminal NxxC motif of a peptide for macrocyclization. This study furthers our understanding of the variety of PTMs involved in creating the structure diversity of macrocyclic RiPPs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfuros
/
Flavoproteínas
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2023
Tipo del documento:
Article
País de afiliación:
China