Discovery of the Lanthipeptide Curvocidinâ
and Structural Insights into its Trifunctional Synthetase CuvL.
Angew Chem Int Ed Engl
; 62(23): e202302490, 2023 06 05.
Article
em En
| MEDLINE
| ID: mdl-37014271
ABSTRACT
Lanthipeptides are ribosomally-synthesized natural products from bacteria featuring stable thioether-crosslinks and various bioactivities. Herein, we report on a new clade of tricyclic class-IV lanthipeptides with curvocidin from Thermomonospora curvata as its first representative. We obtained crystal structures of the corresponding lanthipeptide synthetase CuvL that showed a circular arrangement of its kinase, lyase and cyclase domains, forming a central reaction chamber for the iterative substrate processing involving nine catalytic steps. The combination of experimental data and artificial intelligence-based structural models identified the N-terminal subdomain of the kinase domain as the primary site of substrate recruitment. The ribosomal precursor peptide of curvocidin employs an amphipathic α-helix in its leader region as an anchor to CuvL, while its substrate core shuttles within the central reaction chamber. Our study thus reveals general principles of domain organization and substrate recruitment of class-IV and class-III lanthipeptide synthetases.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inteligência Artificial
/
Ligases
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha