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Received October 10, 2021
Accepted January 8, 2022
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Energy metabolism in Chinese hamster ovary (CHO) cells: Productivity and beyond
Department of Biological Sciences and Bioengineering, Inha University, 100, Inha-ro, Michuhol-gu, Incheon 22212, Korea
Korean Journal of Chemical Engineering, May 2022, 39(5), 1097-1106(10), 10.1007/s11814-022-1062-y
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Abstract
Chinese hamster ovary (CHO) cell lines have been widely used to produce recombinant proteins. While the biosynthesis of recombinant proteins is energy-intensive, CHO cells exhibit inefficient metabolism, characterized by rapid conversion of glucose to lactate, possibly leading to lower cell growth and productivity of therapeutic proteins. Therefore, it is important to understand and engineer cellular metabolism to increase recombinant protein production. In this review, cellular energy metabolism of CHO cells with respect to protein synthesis is overviewed. Then, genetic and process engineering approaches to enhance metabolic efficiency are described, resulting in the improvement of cell culture performance. Finally, recent modeling technologies for understanding and predicting cellular metabolic behaviors are reviewed. These efforts will aid to further advance the biomanufacturing of therapeutic proteins.
Keywords
References
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Leong DS, Tan JC, Chin CL, Mak SY, Ho YS, Ng SK, Sci. Rep., 7, 45216 (2017)
Leong DSZ, Teo BKH, Tan JGL, Kamari H, Yang YS, Zhang P, Ng SK, Sci. Rep., 8, 4037 (2018)
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Torres M, Berrios J, Rigual Y, Latorre Y, Vergara M, Dickson AJ, Altamirano C, Chem. Eng. Sci., 205, 201 (2019)
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Calleja LL, Lecina M, Repullo JL, Albiol J, Sola C, Cairo JJ, Appl. Microbiol. Biotechnol., 99, 9951 (2015)
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Mulukutla BC, Kale J, Kalomeris T, Jacobs M, Hiller GW, Biotechnol. Bioeng., 114, 1779 (2017)
Calmels C, McCann A, Malphettes L, Andersen MR, Metab Eng., 51, 9 (2019)
Yahia BB, Malphettes L, Heinzle E, Appl. Microbiol. Biotechnol., 99, 7009 (2015)
Huang Z, Lee DY, Yoon S, Biotechnol. Bioeng., 114, 2717 (2017)
Kyriakopoulos S, Ang KS, Lakshmanan M, Huang Z, Yoon S, Gunawan R, Lee DY, Biotechnol. J., 13, e1700229 (2018)
Tang P, Xu J, Louey A, Tan Z, Yongky A, Liang S, Li ZJ, Weng Y, Liu S, Crit. Rev. Biotechnol., 40, 265 (2020)
Sha S, Huang Z, Wang Z, Yoon S, Curr. Opin. Chem. Eng., 22, 54 (2018)
Islam MM, Schroeder WL, Saha R, Curr. Opin. Syst. Biol., 26, 72 (2021)
Stalidzans E, Seiman A, Peebo K, Komasilovs V, Pentjuss A, Biochem. Soc. Trans., 46, 261 (2018)
Gutierrez JM, Lewis NE, Biotechnol. J., 10, 939 (2015)
Rejc Z, Magdevska L, Trselic T, Osolin T, Vodopivec R, Mraz J, Pavliha E, Zimic N, Cvitanović T, Rozman D, Moškon M, Comput. Biol. Med., 88, 150 (2017)
Altamirano C, Illanes A, Becerra S, Cairo JJ, Godia F, J. Biotechnol., 125, 547 (2006)
Sheikholeslami Z, Jolicoeur M, Henry O, Biotechnol. Prog., 30, 535 (2014)
O'Brien CM, Zhang Q, Daoutidis P, Hu WS, Metab Eng., 66, 31 (2021)
Yahia BB, Malphettes L, Heinzle E, Metab Eng., 66, 204 (2021)
Selvarasu S, Kim DY, Karimi IA, Lee DY, J. Biotechnol., 150, 94 (2010)
Zhanga Y, Lin H, Yanga Z, Wanga J, Sun Y, Xu B, Zhao Z, J. Biomed. Inform., 99, 103294 (2019)
Schmitt J, Downey B, Beller J, Russell B, Quach A, Lyon D, Curran M, Mulukutla BC, Chu C, Biotechnol. Bioeng., 116, 2223 (2019)
Schinn SM, Morrison C, Wei W, Zhang L, Lewis NE, Biotechnol. Bioeng., 118, 2118 (2021)
Huang Z, Xu J, Yongkyb A, Morrisa CS, Polancoa AL, Reilyc M, Borysb MC, Lib ZJ, Yoon S, Biochem. Eng. J., 160, 1076938 (2020)
Calmels C, Arnoult S, Yahia BB, Malphettes L, Andersen MR, Metab. Eng., 9, e00097 (2019)
Huang Z, Yoon S, Processes, 8, 331 (2020)
Luo Y, Lovelett RJ, Price JV, Radhakrishnan D, Barnthouse K, Hu P, Schaefer E, Cunningham J, Lee KH, Shivappa RB, Ogunnaike BA, Biotechnol. J., 16, e2000261 (2021)
van Rosmalen RP, Smith RW, dos Santos VAPM, Fleck C, Suarez-Diez M, Metab. Eng., 64, 74 (2021)
Yeo HC, Hong J, Lakshmanan M, Lee DY, Metab. Eng., 60, 138 (2020)
