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Enzymatic Synthesis of the C-Glycosidic Moiety of Nogalamycin R.

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 ?-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 ?-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.

SUBMITTER: Siitonen V

PROVIDER: S-EPMC6203184 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Enzymatic Synthesis of the C-Glycosidic Moiety of Nogalamycin R.

Siitonen Vilja V Nji Wandi Benjamin B Törmänen Akke-Pekka AP Metsä-Ketelä Mikko M

ACS chemical biology 20180820 9

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 enz ...[more]

PMID: 30114358

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