Ketoolivosyl-tetracenomycin C: A new ketosugar bearing tetracenomycin reveals new insight into the substrate flexibility of glycosyltransferase ElmGT

S. Eric Nybo, Khaled A. Shabaan, Madan K. Kharel, Happy Sutardjo, José A. Salas, Carmen Méndez, Jürgen Rohr

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)2247-2250
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number6
DOIs
StatePublished - Mar 15 2012

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (Grant CA 091901 to JR) and a predoctoral fellowship from the University of Kentucky graduate school to E.N.

Keywords

  • Combinatorial biosynthesis
  • Elloramycin
  • Glycosyltransferase
  • Ketosugar
  • Polyketide
  • Streptomyces

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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