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

  作者 Nybo, SE; Shabaan, KA; Kharel, MK; Sutardjo, H; Salas, JA; Mendez, C; Rohr, J  
  选自 期刊  Bioorganic & Medicinal Chemistry Letters;  卷期  2012年22-6;  页码  2247-2250  
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[摘要]A new tetracenomycin analog, 8-demethyl-8-(4'-keto)-alpha-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. (C) 2012 Elsevier Ltd. All rights reserved.

 
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