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

Bioorganic & medicinal chemistry letters 2012 Mar 15

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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. Copyright Â© 2012 Elsevier Ltd. All rights reserved.

Citation

S Eric Nybo, Khaled A Shabaan, Madan K Kharel, Happy Sutardjo, José A Salas, Carmen Méndez, Jürgen Rohr. Ketoolivosyl-tetracenomycin C: a new ketosugar bearing tetracenomycin reveals new insight into the substrate flexibility of glycosyltransferase ElmGT. Bioorganic & medicinal chemistry letters. 2012 Mar 15;22(6):2247-50