Biosynthetic Origin of the Atypical Stereochemistry in the Thioheptose Core of Albomycin Nucleoside Antibiotics.
J Am Chem Soc
; 141(6): 2211-2214, 2019 02 13.
Article
em En
| MEDLINE
| ID: mdl-30673214
ABSTRACT
Albomycins are peptidyl thionucleoside natural products that display antimicrobial activity against clinically important pathogens. Their structures are characterized by a thioheptose with atypical stereochemistry including a d-xylofuranose ring modified with a d-amino acid moiety. Herein it is demonstrated that AbmH is a pyridoxal 5'-phosphate (PLP)-dependent transaldolase that catalyzes a threo-selective aldol-type reaction to generate the thioheptose core with a d-ribofuranose ring and an l-amino acid moiety. The conversion of l-to d-amino acid configuration is catalyzed by the PLP-dependent epimerase AbmD. The d- ribo to d- xylo conversion of the thiofuranose ring appears according to gene deletion experiments to be mediated by AbmJ, which is annotated as a radical S-adenosyl-l-methionine (SAM) enzyme. These studies establish several key steps in the assembly of the thioheptose core during the biosynthesis of albomycins.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ferricromo
/
Heptoses
/
Antibacterianos
/
Nucleosídeos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article