Biochemical and Structural Insights of the Early Glycosylation Steps in Calicheamicin Biosynthesis

Journal Article · Wed Sep 17 04:00:00 EDT 2008 · Chem. Biol.

DOI:https://doi.org/10.1016/j.chembiol.2008.06.011· OSTI ID:1006814

Zhang, Changsheng; Bitto, Eduard; Goff, Randal D; Singh, Shanteri; Bingman, Craig A; Griffith, Byron R; Albermann, Christoph; Thorson, Jon S ^[1]

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1. UW

The enediyne antibiotic calicheamicin (CLM) {gamma}{sub 1}{sup I} 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006814
• Journal Information: Chem. Biol., Journal Name: Chem. Biol. Journal Issue: (8) ; 08, 2008 Vol. 15; ISSN 1554-8929
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ANTIBIOTICS
AROMATICS
BIOSYNTHESIS
CARBOHYDRATES
DNA
FUNCTIONALS