Author/Authors :
Changsheng Zhang a، نويسنده , , Eduard Bitto and David B. McKay، نويسنده , , Randal D. Goff، نويسنده , , Shanteri Singh، نويسنده , , Craig A. Bingman، نويسنده , , Byron R. Griffith، نويسنده , , Christoph Albermann، نويسنده , , Gary E. Wesenberg and George N. Phillips Jr.، نويسنده , , Jon S. Thorson، نويسنده ,
Abstract :
The enediyne antibiotic calicheamicin (CLM) γ1I is a prominent antitumor agent that is targeted to DNA by a novel aryltetrasaccharide comprised of an aromatic unit and four unusual carbohydrates. Herein we report the heterologous expression and the biochemical characterization of the two “internal” glycosyltransferases CalG3 and CalG2 and the structural elucidation of an enediyne glycosyltransferase (CalG3). In conjunction with the previous characterization of the “external” CLM GTs CalG1 and CalG4, this study completes the functional assignment of all four CLM GTs, extends the utility of enediyne GT-catalyzed reaction reversibility, and presents conclusive evidence of a sequential glycosylation pathway in CLM biosynthesis. This work also reveals the common GT-B structural fold can now be extended to include enediyne GTs.
