Formation of an aminovinyl-cysteine residue in thioviridamides occurs through a path independent of known lanthionine synthetase activity.
Cell Chem Biol
; 28(5): 675-685.e5, 2021 05 20.
Article
en En
| MEDLINE
| ID: mdl-33476565
ABSTRACT
2-Aminovinyl-cysteine (AviCys) is a thioether amino acid shared by a variety of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Based on investigations into the biosynthesis of thioviridamide RiPPs in Streptomyces sp. NRRL S-87, we here report a path for the formation of this unusual thioether residue. This path relies on four dedicated proteins phosphotransferase TvaCS-87, Lyase TvaDS-87, kinase homolog TvaES-87, and LanD-like flavoprotein TvaFS-87. TvaES-87 plays a critical role in effective AviCys formation. During the posttranslational modifications of the precursor peptide, it works with TvaFS-87 to form a minimum AviCys synthetase complex, which follows the combined activity of TvaCDS-87 for Thr dehydration and catalyzes Cys oxidative decarboxylation and subsequent Michael addition of the resulting enethiol nucleophile onto the newly formed dehydroamino acid residue for cyclization. With TvaES-87, TvaFS-87 activity for Cys processing can be coordinated with TvaCDS-87 activity for minimizing competitive or unexpected spontaneous reactions and forming AviCys effectively.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
/
Tioamidas
/
Cisteína
/
Hidroliasas
/
Complejos Multienzimáticos
Idioma:
En
Revista:
Cell Chem Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
China