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Evaluation and use of disaccharides as energy source in protein-free mammalian cell cultures


From Left: Mak Shi Ya, Dr Ho Ying Swan, Dr Ng Say Kong, Dawn Leong, Christine Chin, Dr Janice Tan

Authors

Dawn Sow Zong Leong 1, Janice Gek Ling Tan 1, Christine Lin Chin 1, Shi Ya Mak 1, Ying Swan Ho 1, Say Kong Ng 1, 2

1 Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore
2 Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore

Published in Scientific Reports 2017 7: 45216 (Online Version)

 

Abstract

Cell membranes are made of phospholipids which have very low permeability to sugars. Hence, mammalian cells are generally considered to only take up simple sugars, enabled by transporter proteins on the cell membrane that allows these simple sugars to enter them. More complex sugars such as disaccharides (sugars with 2 joint units of simple sugar monomers) and other carbohydrates are to be broken down into simple sugars in the digestive system and in the blood stream, before our cells can utilize them.

In the production of recombinant proteins, mammalian cells are typically cultivated using glucose, a simple sugar, as an energy source, as serum or enzymes that can break down complex sugars are not added to the bioreactors for safety and economic reasons. In this study, we successfully cultivated mammalian cells using a more complex sugar – maltose which is a disaccharide consisting of 2 glucose units – as an energy source Our results are significant because there is no known transporter for maltose in mammalian cells, and the cells that we used (CHO and HEK293) are not known to express secreted or transmembrane enzymes that can break down maltose. Therefore, our findings set the stage for future research to explore this currently unknown mechanism that would be important to further our understanding of mammalian cell sugar metabolism. In addition, this discovery can potentially be applied to improve the production of biologicsusing serum-free mammalian cell cultures. To our knowledge, this is the first report of a protein-free mammalian cell culture using disaccharides as an energy source.


Figure 1. Hydrolysis of Maltose into 2 Glucose units.

 

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