Modulation of deoxysugar transfer by the elloramycin glycosyltransferase ElmGT through site-directed mutagenesis.

نویسندگان

  • Angelina Ramos
  • Carlos Olano
  • Alfredo F Braña
  • Carmen Méndez
  • José A Salas
چکیده

The glycosyltransferase ElmGT from Streptomyces olivaceus is involved in the biosynthesis of the antitumor drug elloramycin, and it has been shown to possess a broad deoxysugar recognition pattern, being able to transfer different l- and d-deoxysugars to 8-demethyl-tetracenomycin C, the elloramycin aglycone. Site-directed mutagenesis in residues L309 and N312, located in the alpha/beta/alpha motif within the nucleoside diphosphate-sugar binding region, can be used to modulate the substrate flexibility of ElmGT, making it more precise for transfer of specific deoxysugars.

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Combining sugar biosynthesis genes for the generation of L- and D-amicetose and formation of two novel antitumor tetracenomycins.

L- and D-stereoisomers of amicetose were generated by combining sugar biosynthesis genes from four different antibiotic gene clusters and both sugars were transferred to the elloramycin aglycone by the sugar flexible ElmGT glycosyltransferase.

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عنوان ژورنال:
  • Journal of bacteriology

دوره 191 8  شماره 

صفحات  -

تاریخ انتشار 2009