1.
J Am Chem Soc
; 144(32): 14838-14845, 2022 08 17.
Artigo
em Inglês
| MEDLINE
| ID: mdl-35905381
RESUMO
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.