A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis.
Proc Natl Acad Sci U S A
; 105(5): 1460-5, 2008 Feb 05.
Article
en En
| MEDLINE
| ID: mdl-18223152
ABSTRACT
The enediynes, unified by their unique molecular architecture and mode of action, represent some of the most potent anticancer drugs ever discovered. The biosynthesis of the enediyne core has been predicted to be initiated by a polyketide synthase (PKS) that is distinct from all known PKSs. Characterization of the enediyne PKS involved in C-1027 (SgcE) and neocarzinostatin (NcsE) biosynthesis has now revealed that (i) the PKSs contain a central acyl carrier protein domain and C-terminal phosphopantetheinyl transferase domain; (ii) the PKSs are functional in heterologous hosts, and coexpression with an enediyne thioesterase gene produces the first isolable compound, 1,3,5,7,9,11,13-pentadecaheptaene, in enediyne core biosynthesis; and (iii) the findings for SgcE and NcsE are likely shared among all nine-membered enediynes, thereby supporting a common mechanism to initiate enediyne biosynthesis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polienos
/
Proteína Transportadora de Acilo
/
Sintasas Poliquetidas
/
Enediinos
/
Antibióticos Antineoplásicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos