title: Complete set of glycosyltransferase structures in the calicheamicin biosynthetic pathway reveals the origin of regiospecificity.
abstract: Glycosyltransferases are useful synthetic catalysts for generating natural products with sugar moieties. Although several natural product glycosyltransferase structures have been reported, design principles of glycosyltransferase engineering for the generation of glycodiversified natural products has fallen short of its promise, partly due to a lack of understanding of the relationship between structure and function. Here, we report structures of all four calicheamicin glycosyltransferases (CalG1, CalG2, CalG3, and CalG4), whose catalytic functions are clearly regiospecific. Comparison of these four structures reveals a conserved sugar donor binding motif and the principles of acceptor binding region reshaping. Among them, CalG2 possesses a unique catalytic motif for glycosylation of hydroxylamine. Multiple glycosyltransferase structures in a single natural product biosynthetic pathway are a valuable resource for understanding regiospecific reactions and substrate selectivities and will help future glycosyltransferase engineering.
authors: Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
authors: Aram
authors: A
authors: Chang
authors: Shanteri
authors: S
authors: Singh
authors: Kate E
authors: KE
authors: Helmich
authors: Randal D
authors: RD
authors: Goff
authors: Craig A
authors: CA
authors: Bingman
authors: Jon S
authors: JS
authors: Thorson
authors: George N
authors: GN
authors: Phillips
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D002241:Carbohydrates / Q000737:chemistry; D053281:Enediynes / Q000737:chemistry; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism*; D006898:Hydroxylamines / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D002241:Carbohydrates; D053281:Enediynes; D006898:Hydroxylamines; D016695:Glycosyltransferases