Hybrid glycosylated products and their production and use

C - Chemistry – Metallurgy – 12 – P

Patent

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Details

C12P 19/00 (2006.01) C07H 17/08 (2006.01) C12N 1/00 (2006.01) C12N 1/21 (2006.01) C12N 9/10 (2006.01) C12N 15/52 (2006.01) C12N 15/54 (2006.01) C12N 15/76 (2006.01) C12P 19/62 (2006.01)

Patent

CA 2405958

The present invention relates to hybrid glycosylated products, and in particular, to natural products such as polyketides and glycopeptides, and to processes for their preparation. The invention is particularly concerned with recombinant cells in which a cloned microbial glycosyltransferase can be conveniently screened for its ability to generate specific glycosylated derivatives when supplied with polyketide, peptide, or polyketide-peptides as substrates. The invention demonstrates that cloned glycosyltransferases when rapidly screened for their ability to attach a range of activated sugars to a range of exogenously supplied or endogenously generated aglycone templates, show a surprising flexibility towards both aglycone and sugar substrates, and that this process allows the production of glycosylated polyketides in good yield. This overcomes the problem not only of supplying novel sugar attachments to individual polyketides, including polyketides altered by genetic engineering, but also of increasing the diversity of polyketide libraries by combinatorial attachment of sugars.

La présente invention concerne des produits hybrides glycosylés et, en particulier, des produits naturels tels que les polykétides et les glycopeptides, et leurs procédés de préparation. L'invention concerne en particulier des cellules de recombinaison dans lesquelles une glycosyltransférase microbienne clonée peut être facilement criblée pour sa capacité à générer des dérivés glycosylés spécifiques lorsqu'elle est associée à des substrats formés par des polykétides, des peptides, ou des polykétides-peptides. L'invention démontre que les glycosyltransférases clonées, rapidement criblées pour leur capacité à fixer une quantité de sucres activés à une quantité de matrices d'aglycone obtenues de façon exogène ou générées de façon endogène, présentent une flexibilité surprenante par rapport aux substrats d'aglycone et de sucre, et que ce procédé permet d'obtenir un bon rendement de polykétides glycosylés. Ceci permet non seulement de résoudre le problème lié aux nouvelles fixations de sucre à fournir aux polykétides individuels, y compris des polykétides altérés par génie génétique, mais aussi d'augmenter la diversité des bibliothèques de polykétides par des fixations de sucres combinatoires.

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