Comparative phenotypic analysis of CHO clones and culture media for lactate shift

• Published in: Journal of biotechnology 2018-10, Vol.283, p.97-104
• Main Authors: Hong, Jong Kwang, Nargund, Shilpa, Lakshmanan, Meiyappan, Kyriakopoulos, Sarantos, Kim, Do Yun, Ang, Kok Siong, Leong, Dawn, Yang, Yuansheng, Lee, Dong-Yup
• Format: Article
• Language: English
• Subjects: Alanine; Animals; Aspartic Acid - metabolism; Carbon balance analysis; Cell Culture Techniques - methods; Cell Proliferation; CHO Cells; Cricetinae; Cricetulus; Culture Media - chemistry; Glutamine - metabolism; Glutamine depletion; Lactate shift; Lactic Acid - chemistry; Metabolic Networks and Pathways; Multivariate statistical analysis; Phenotype; Serine - metabolism
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/j.jbiotec.2018.07.042

•Explored the effects of media and clonal variation on the lactate shift in CHO cells.•Conducted multivariate statistical analysis of various CHO cell cultures.•Found glutaminolysis as preferred pathway for lactate production by pyruvate supply.•Understood the balanced selection of clone and media composition for lactate shift. We explored the effects of media and clonal variation on the lactate shift which can be considered as one of the desirable features in CHO cell culture. Various culture profiles with the specific growth and antibody production rates under three different media conditions in two CHO producing clones were evaluated by resorting to multivariate statistical analysis. In most cases, glutamine depletion coincided with lactate consumption, suggesting that glutaminolysis rather than glycolysis was the preferred pathway for the pyruvate supply toward lactate production. With respect to the lactate shift, high performing medium showed higher glutamate uptake, higher aspartate secretion and lower serine uptake compared to other media conditions. In addition, clone itself exhibited the desired lactate consumption more consistently accompanying with distinguishing phenotype. The clone exhibiting lactate shift produced lesser lactate in exponential phase but two-fold higher non-toxic alanine, thus leading to better culture environment. Thus, we understand the balanced selection of clone and media composition enables cells to utilize the metabolic pathways for the desired lactate shift.