Expanding the Substrate Scope of Acyltransferase LovD9 for the Biosynthesis of Statin Analogues.
Chemistry
; 29(42): e202300911, 2023 Jul 26.
Article
em En
| MEDLINE
| ID: mdl-37139626
ABSTRACT
This study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by the laboratory evolved acyltransferase LovD9. Vinyl and p-nitrophenyl esters have emerged as alternate substrates for LovD9-catalyzed acylation. While vinyl esters can reach product yields as high as the ones obtained by α-dimethyl butyryl-S-methyl-3-mercaptopropionate (DMB-SMMP), the thioester for which LovD9 was evolved, p-nitrophenyl esters display a reactivity even higher than DMB-SMMP for the first acylation step yet the acylation product yield is lower. The reaction mechanisms were elucidated through quantum mechanics (QM) calculations.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Hidroximetilglutaril-CoA Redutases
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article