Enzymatic Synthesis of the C-Glycosidic Moiety of Nogalamycin R.
ACS Chem Biol
; 13(9): 2433-2437, 2018 09 21.
Article
em En
| MEDLINE
| ID: mdl-30114358
ABSTRACT
Carbohydrate moieties are essential for the biological activity of anthracycline anticancer agents such as nogalamycin, which contains l-nogalose and l-nogalamine units. The former of these is attached through a canonical O-glycosidic linkage, but the latter is connected via an unusual dual linkage composed of C-C and O-glycosidic bonds. In this work, we have utilized enzyme immobilization techniques and synthesized l-rhodosamine-thymidine diphosphate (TDP) from α-d-glucose-1-TDP using seven enzymes. In a second step, we assembled the dual linkage system by attaching the aminosugar to an anthracycline aglycone acceptor using the glycosyl transferase SnogD and the α-ketoglutarate dependent oxygenase SnoK. Furthermore, our work indicates that the auxiliary P450-type protein SnogN facilitating glycosylation is surprisingly associated with attachment of the neutral sugar l-nogalose rather than the aminosugar l-nogalamine in nogalamycin biosynthesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Streptomyces
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Nogalamicina
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Enzimas Imobilizadas
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Antibióticos Antineoplásicos
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2018
Tipo de documento:
Article