Non-Heme Iron Enzymes Catalyze Heterobicyclic and Spirocyclic Isoquinolone Core Formation in Piperazine Alkaloid Biosynthesis.
Angew Chem Int Ed Engl
; 63(20): e202401324, 2024 05 13.
Article
em En
| MEDLINE
| ID: mdl-38499463
ABSTRACT
We report the discovery and biosynthesis of new piperazine alkaloids-arizonamides, and their derived compounds-arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non-heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3-alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alcaloides
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2024
Tipo de documento:
Article