Novel Strategies for Improving Cell Viability and Production Yield

  • Hisahiro Tabuchi
  • Tomoya Sugiyama
  • Satoshi Tainaka
Conference paper
Part of the ESACT Proceedings book series (ESACT, volume 5)


Transporters play a crucial role in regulating cell metabolism, so we hypothesized that some transporters might be suitable targets for cell engineering to enhance MAb yield. The taurine transporter (TAUT) is stably expressed in CHO-DXB11 cells and may not only transport organic osmolytes but also alter the net cellular content of osmolytes, thereby affecting cell function. We found that MAb1/DXB11/TAUT cells that expressed pHyg-TAUT had higher MAb1 yield (p < 0.01) and lower lactate production (p < 0.05). One high-yield MAb1/DXB11/TAUT cell line (T10) maintained >80% viability for more than 1 month. T10 cells also showed suppression of ammonia accumulation and activation of glutathione metabolism. Their higher glutamine consumption may contribute to their increased viability and yield. These results demonstrate that overexpression of TAUT enhances cell culture performance by prolonging the culture period and increasing MAb yield. A further challenge was to find a way to modify the metabolic machinery for even high yields in a shorter culture period. We therefore engineered T10 cells to co-overexpress alanine aminotransferase (ALT1), which participates in the glucose-alanine cycle. We found that co-overexpression of ALT1 and TAUT gave even higher yield in 1-L bioreactors in a shorter time (5.3 g/L on Day 21).


Culture Period Parent Cell Bioreactor Culture Taurine Transporter Improve Cell Viability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by a grant from the Bioprocess Development Project of the New Energy and Industrial Technology Development Organization (NEDO), Japan.


  1. Amores-Sanchez MI, Medina MA. (1999). Glutamine, as a precursor of glutathione, and oxidative stress. Mol Genet Metab 67(2):100–105.PubMedCrossRefGoogle Scholar
  2. Burg MB, Ferraris JD. (2008). Intracellular organic osmolytes: function and regulation. J Biol Chem 283(12):7309–7313.PubMedCrossRefGoogle Scholar
  3. Garcia-Campusano F, Anaya VH, Robledo-Arratia L, Quezada H, Hernandez H, Riego L, Gonzalez A. (2009). ALT1-encoded alanine aminotransferase plays a central role in the metabolism of alanine in saccharomyces cerevisiae. Can J Microbiol 55(4):368–374.PubMedCrossRefGoogle Scholar
  4. Han X, Patters AB, Jones DP, Zelikovic I, Chesney RW. (2006). The taurine transporter: mechanisms of regulation. Acta Physiol (Oxf) 187(1–2):61–73.CrossRefGoogle Scholar
  5. Lang KS, Fillon S, Schneider D, Rammensee HG, Lang F. (2002). Stimulation of TNF alpha expression by hyperosmotic stress. Pflugers Arch 443(5–6):798–803.PubMedGoogle Scholar
  6. Zielke HR, Zielke CL, Ozand PT. (1984). Glutamine: a major energy source for cultured mammalian cells. Fed Proc 43(1):121–125.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Hisahiro Tabuchi
    • 1
  • Tomoya Sugiyama
    • 2
  • Satoshi Tainaka
    • 2
  1. 1.API Process Development Dept. (Bio Technology) Pharmaceutical Technology Div.Kitaku, TokyoJapan
  2. 2.Chugai Pharmaceutical Co., Ltd., Kita-KuKitakuJapan

Personalised recommendations