Biosynthesis of cmp-legionaminic acid from fructose-6-p, and...

C - Chemistry – Metallurgy – 12 – P

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C12P 19/32 (2006.01) C07H 19/16 (2006.01) C12P 19/00 (2006.01) C12P 19/26 (2006.01) C12P 19/30 (2006.01)

Patent

CA 2747214

The sialic acid-like sugar legionaminic acid is found as a virulence-associated surface glyco-conjugate in Legionella pneumophila and Campylobac-ter coli. In this work, we have purified and biochemical-ly characterized eleven candidate biosynthetic enzymes from C. jejuni, thereby fully reconstituting the biosyn-thesis of legionaminic acid and its CMP-activated form, starting from fructose-6-P. This pathway involves unique GDP-linked intermediates and provides a facile means for the efficient large-scale synthesis of an im-portant sialic acid mimic and novel precursors.

Le glucide de type acide, acide légionaminique, est observé en tant que glycoconjugué de surface associé à la virulence chez Legionella pneumophila et Campylobacter coli. Selon la présente invention, nous avons purifié et caractérisé sur le plan biochimique onze enzymes biosynthétiques candidates de C. jejuni, de manière à reconstituer totalement la biosynthèse d'acide légionaminique et sa forme CMP-activée, à partir de fructose-6-P. Cette voie met en uvre des intermédiaires GDP-liés uniques et constitue un moyen facile pour la synthèse à grande échelle efficace d'un mimétique d'acide sialique important et de nouveaux précurseurs.

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