Chemical and biosynthetic evolution of the antimycin-type depsipeptides.
Mol Biosyst
; 9(11): 2712-9, 2013 Nov.
Article
en En
| MEDLINE
| ID: mdl-23989727
ABSTRACT
Evolution of natural products, and particularly those resulting from microbial assembly line-like enzymes, such as polyketide (PK) and nonribosomal peptides (NRP), has resulted in a variety of pharmaceutically important and chemically diverse families of molecules. The antimycin-type depsipeptides are one such grouping, with a significant level of diversity and members that have noted activities against key targets governing human cellular apoptosis (e.g. Bcl-xL and GRP78). Chemical variance originates from ring size, with 9-, 12-, 15-, and 18-membered classes, and we show that such distinctions influence their molecular targeting. Further, we present here a systematic interrogation of the chemistry and assembly line evolution of antimycin-type analogues by conducting metabolomic profiling and biosynthetic gene cluster comparative analysis of the depsipeptide assembly lines for each member of the antimycin-group. Natural molecular evolution principles of such studies should assist in artificial re-combinatorializing of PK and NRP assembly lines.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Productos Biológicos
/
Depsipéptidos
Límite:
Humans
Idioma:
En
Revista:
Mol Biosyst
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Canadá