RebG- and RebM-catalyzed indolocarbazole diversification.
Chembiochem
; 7(5): 795-804, 2006 May.
Article
en En
| MEDLINE
| ID: mdl-16575939
ABSTRACT
Rebeccamycin and staurosporine represent two broad classes of indolocarbazole glycoside natural products with antitumor properties. Based upon previous sequence annotation and in vivo studies, rebG encodes for the rebeccamycin N-glucosyltransferase, and rebM for the requisite 4'-O-methyltransferase. In the current study, an efficient in vivo biotransformation system for RebG was established in both Streptomyces lividans and Escherichia coli. Bioconversion experiments revealed RebG to glucosylate a set of indolocarbazole surrogates, the products of which could be further modified by in vitro RebM-catalyzed 4'-O-methylation. Both RebG and RebM displayed substrate promiscuity, and evidence for a remarkable lack of RebG regioselectivity in the presence of asymmetric substrates is also provided. In the context of the created indolocarbazole analogues, cytotoxicity assays also highlight the importance of 4'-O-methylation for their biological activity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Bacterianas
/
Carbazoles
/
Glucosiltransferasas
/
Indoles
/
Metiltransferasas
Límite:
Humans
Idioma:
En
Revista:
Chembiochem
Asunto de la revista:
BIOQUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos