Engineered Cytochrome P450-Catalyzed Oxidative Biaryl Coupling Reaction Provides a Scalable Entry into Arylomycin Antibiotics.
J Am Chem Soc
; 144(32): 14838-14845, 2022 08 17.
Article
em En
| MEDLINE
| ID: mdl-35905381
ABSTRACT
We report herein the first example of a cytochrome P450-catalyzed oxidative carbon-carbon coupling process for a scalable entry into arylomycin antibiotic cores. Starting from wild-type hydroxylating cytochrome P450 enzymes and engineered Escherichia coli, a combination of enzyme engineering, random mutagenesis, and optimization of reaction conditions generated a P450 variant that affords the desired arylomycin core 2d in 84% assay yield. Furthermore, this process was demonstrated as a viable route for the production of the arylomycin antibiotic core on the gram scale. Finally, this new entry affords a viable, scalable, and practical route for the synthesis of novel Gram-negative antibiotics.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Sistema Enzimático do Citocromo P-450
/
Antibacterianos
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2022
Tipo de documento:
Article