Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 411704
Title Molecular characterization and optimization of enzymes involved in glycosaminoglycan biosynthesis
Author(s) Raedts, J.G.J.
Source University. Promotor(en): John van der Oost, co-promotor(en): Servé Kengen. - [S.l.] : S.n. - ISBN 9789461730190 - 154
Department(s) Microbiological Laboratory
VLAG
Publication type Dissertation, internally prepared
Publication year 2011
Keyword(s) glycosaminoglycanen - hyaluronzuur - heparine - biosynthese - escherichia coli - genexpressie - glycosaminoglycans - hyaluronic acid - heparin - biosynthesis - gene expression
Categories Genetic Engineering / Industrial Microbiology
Abstract

Glycosaminoglycans are biological active polysaccharides composed of repeating disaccharides composed of a hexuronic acid and a hexosamine. They have various pharmaceutical applications and traditionally this type of molecule is isolated from animal tissue. Since extraction from animal derivatives has serious limitations for the production of a large variety of defined glycosaminoglycans, there is a general interest in developing alternative systems enabling a more tightly controlled synthesis. During this research project we explored alternative ways of controlled chemo-enzymatic synthesis ofmonodisperse and uniform glycosaminoglycans for pharmaceutical applications, with a main focus on heparin. Heparin is a highly sulfated and complex glycosaminoglycan which is worldwide used as an anticoagulant to prevent blood clotting during surgery.Upon closer investigation of the heparin biosynthesis the D-glucuronyl C5-epimerase was recognized as a key enzyme, as this is the only reaction that cannot be done chemically. Two alternative approaches were taken to get closer to an industrial applicable enzyme; improvement of the animal heparin sulfate D-glucuronyl C5-epimerase and identification and isolation of novel candidate C5-epimerases from prokaryotes. Both approaches gave functional production of C5-epimerases.

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