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.
|Number of pages||4|
|Journal||Bioorganic and Medicinal Chemistry Letters|
|State||Published - Mar 15 2012|
Bibliographical noteFunding 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.
- Combinatorial biosynthesis
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry