title: Ketoolivosyl-tetracenomycin C: a new ketosugar bearing tetracenomycin reveals new insight into the substrate flexibility of glycosyltransferase ElmGT.
abstract: A new tetracenomycin analog, 8-demethyl-8-(4'-keto)-α-L-olivosyl-tetracenomycin C, was generated through combinatorial biosynthesis. Streptomyces lividans TK 24 (cos16F4) was used as a host for expression of a 'sugar plasmid' (pKOL) directing the biosynthesis of NDP-4-keto-L-olivose. This strain harbors all of the genes necessary for production of 8-demethyl-tetracenomycin C and the sugar flexible glycosyltransferase ElmGT. To the best of our knowledge, this report represents the first characterization of a tetracenomycin derivative decorated with a ketosugar moiety. Also, as far as we know, 4-keto-L-olivose has only been described as an intermediate of oleandomycin biosynthesis, but has not been described before as an appendage for a polyketide compound. Furthermore, this report gives further insight into the substrate flexibility of ElmGT to include an NDP-ketosugar, which is unusual and is rarely observed among glycosyltransferases from antibiotic biosynthetic pathways.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.
authors.forename: S Eric
authors.initials: SE
authors.lastname: Nybo
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Shabaan
authors.forename: Madan K
authors.initials: MK
authors.lastname: Kharel
authors.forename: Happy
authors.initials: H
authors.lastname: Sutardjo
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rohr
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D052978:Disk Diffusion Antimicrobial Tests; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D016695:Glycosyltransferases / Q000737:chemistry* / Q000378:metabolism; D048170:Streptomyces lividans / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C573026:ketoolivosyl-tetracenomycin C; D016695:Glycosyltransferases