Biosynthetic pathway deflection – a new cell line engineering approach

Von, Rose Thomas, Sandig, Sandig Volker

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 771
• Langue: English

Extrait

von Horstenet al.BMC Proceedings2011,5(Suppl 8):O4 http://www.biomedcentral.com/17536561/5/S8/O4

M E E T I N GA B S T R A C TOpen Access Biosynthetic pathway deflection–a new cell line engineering approach * Hans Henning von Horsten, Thomas Rose, Volker Sandig From22nd European Society for Animal Cell Technology (ESACT) Meeting on Cell Based Technologies Vienna, Austria. 1518 May 2011

With increasing information on genome, transcriptome and metabolome of commonly used production cell lines, engineering becomes an increasingly popular approach to achieve desired product attributes, growth behavior and nutrient consumption. Tools range from feeding intermediate metabolites, overexpression or deregulation of key enzymes of a pathway to knockout and RNA silencing. While conceptionally simple, the lat ter approaches are either labor intensive or costly to apply at large scale.

Fucose targeted glycoengineering Aiming at glycan modulation we added another princi ple to this toolbox: enzymatic deflection of a biochem ical pathway. Fucose is synthesized inside the cell from GDPmannose via short lived intermediates before it is transported to the Golgi apparatus for attachment to the nascent glycan (Figure 1). A bacterial enzyme is used to redirect synthesis towards a heterologous acti vated hexose that cannot be utilized by the cell resulting in depletion of the natural pathway (deflecting enzyme,

Figure 1Overview of GDPLFucose Biosynthesis showing the point of substrate deflection within the fucose denovo synthesis pathway.

ProBioGen AG, Berlin, Germany

© 2011 Horsten et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.