- Previous Article
- Next Article
- Table of Contents
Korean Journal of Chemical Engineering, Vol.39, No.5, 1097-1106, May, 2022
Energy metabolism in Chinese hamster ovary (CHO) cells: Productivity and beyond
E-mail:
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:Chinese Hamster Ovary (CHO) Cells;Biomanufacturing;Recombinant Protein;Energy Metabolism;Lactate
Metabolic Shift
- Walsh G, Nat. Biotechnol., 36, 1136 (2018)
- Grilo AL, Mantalaris A, Trends Biotechnol., 37, 9 (2019)
- Zhu MM, Mollet M, Hubert RS, Kyung YS, Zhang GG, Handbook of industrial chemistry and biotechnology, 3rd edition, Springer (2017).
- Lai T, Yang Y, Ng SK, Pharmaceuticals, 69, 579 (2013)
- Pereira S, Kildegaard HF, Andersen MR, Biotechnol. J., 13, e1700499 (2018)
- Rosano GL, Ceccarelli EA, Front. Microbiol., 5, 172 (2014)
- Henry MN, MacDonald MA, Orellana CA, Gray PP, Gillard M, Baker K, Nielsen LK, Marcellin E, Mahler S, Martínez VS, Biotechnol. Bioeng., 117, 1187 (2020)
- Hartley F, Walker T, Chung V, Morten K, Biotechnol. Bioeng., 115, 1890 (2018)
- Horvat J, Narat M, Spadiut O, Biotechnol. Prog., 36, e3001 (2020)
- Ivarsson M, Noh H, Morbidelli M, Soos M, Biotechnol. Prog., 31, 347 (2015)
- Cacciatore JJ, Chasin LA, Leonard EF, Biotechnol. Adv., 28, 673 (2010)
- Gonzalez MG, Latorre Y, Zuniga R, Aguillon JC, Molina MC, Altamirano C, Crit. Rev. Biotechnol., 39, 665 (2019)
- Blondeel EJM, Aucoin MG, Biotechnol. Adv., 36, 1505 (2018)
- Beyer B, Schuster M, Jungbauer A, Lingg N, Biotechnol. J., 13, 1700476 (2018)
- Martinez VS, Dietmair S, Quek LE, Hodson MP, Gray P, Nielsen LK, Biotechnol. Bioeng., 110, 660 (2013)
- Young JD, Curr. Opin. Biotechnol., 24, 1108 (2013)
- Rich PR, Biochem. Soc. Trans., 31, 1095 (2003)
- Romanova N, Niemann T, Greiner JFW, Kaltschmidt B, Kaltschmidt C, Noll T, Biotechnol. Bioeng., 118, 2348 (2021)
- Alhuthali S, Kotidis P, Kontoravdi C, Int. J. Mol. Sci., 22, 3290 (2021)
- Lieske PL, Wei W, Crowe KB, Figueroa B, Zhang L, Biotechnol. J., 15, e1900306 (2020)
- Liberti MV, Locasale JW, Trends Biochem. Sci., 41, 211 (2016)
- Heiden MGV, Cantley LC, Thompson CB, Science, 324, 1029 (2009)
- Warburg O, Cancer Res., 9, 148 (1925)
- Hume DA, Radik JL, Ferber E, Weidemann MJ, Biochem. J., 174, 703 (1978)
- DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB, Proc. Natl. Acad. Sci., 104, 19345 (2007)
- Lunt SY, Heiden MGV, Annu. Rev. Cell Dev. Biol., 27, 441 (2011)
- Zu XL, Guppy M, Biochem. Biophys. Res. Commun., 313, 459 (2004)
- Locasale JW, Cantley LC, Cell Metab., 14, 443 (2011)
- Zagari F, Jordan M, Stettler M, Broly H, Wurm FM, N. Biotechnol., 30, 238 (2013)
- Ghorbaniaghdam A, Chen J, Henry O, Jolicoeur M, PLoS One, 9, e90832 (2014)
- Ma N, Ellet J, Okediadi C, Hermes P, McCormick E, Casnocha S, Biotechnol. Prog., 25, 1353 (2009)
- Wahrheit J, Niklas J, Heinzle E, Metab. Eng., 23, 9 (2014)
- Sun YT, Zhao L, Ye Z, Fan L, Liu XP, Tan WS, Biochem. Eng. J., 81, 126 (2013)
- Le H, Kabbur S, Pollastrini L, Sun Z, Mills K, Johnson K, Karypis G, Hu WS, J. Biotechnol., 162, 210 (2012)
- Templeton N, Dean J, Reddy P, Young JD, Biotechnol. Bioeng., 110, 2013 (2013)
- Yong J, Bischof H, Burgstaller S, Siirin M, Murphy A, Malli R, Kaufman RJ, Elife, 8, e49682 (2019)
- Klein MC, Zimmermann K, Schorr S, Landini M, Klemens PAW, Altensell J, Jung M, Krause E, Nguyen D, Helms V, Nat. Commun., 9, 3489 (2018)
- Yoo HC, Park SJ, Nam M, Kang J, Kim K, Yeo JH, Kim JK, Heo Y, Lee HS, Lee MY, Lee CW, Kang JS, Kim YH, Cell Metab., 31, 267 (2020)
- Yoo HC, Yu YC, Sung Y, Han JM, Exp. Mol. Med., 52, 1496 (2020)
- Budge JD, Knight TJ, Povey J, Roobol J, Brown IR, Singh G, Dean A, Turner S, Jaques CM, Young RJ, Racher AJ, Smales CM, Metab. Eng., 57, 203 (2020)
- Li W, Fan Z, Lin Y, Wang TY, Front. Bioeng. Biotechnol., 9, 646363 (2021)
- Houten SM, Violante S, Ventura FV, Wanders RJ, Annu. Rev. Physiol., 78, 23 (2016)
- Gutierrez JM, Feizi A, Li S, Kallehauge TB, Hefzi H, Grav LM, Ley D, Hizal DB, Betenbaugh MJ, Voldborg B, Kildegaard HF, Nat. Commun., 11, 68 (2020)
- Hiller K, Grote A, Scheer M, Munch R, Jahn D, Nucleic Acids Res., 32, 375 (2004)
- Fankhauser N, Maser P, Bioinformatics, 21, 1846 (2005)
- Yang Z, Halim A, Narimatsu Y, Joshi HJ, Steentoft C, Schjoldager KTBG, Schulz MA, Sealover NR, Kayser KJ, Mol. Cell Proteomics., 13, 3224 (2014)
- Kapp LD, Lorsch JR, Annu. Rev. Biochem., 73, 657 (2004)
- Noh SM, Sathyamurthy M, Lee GM, Curr. Opin. Chem. Biol., 2, 391 (2013)
- Tihanyi B, Nyitray L, Drug Discov. Today, 38, 25 (2021)
- Reinhart LDD, Sommeregger W, Gili A, Schafellner S, Castan A, Kaisermayer C, Kunert R, BMC Proc., 9, 36 (2015)
- Kim SH, Lee GM, Appl. Microbiol. Biotechnol., 74, 152 (2007)
- Jeon MK, Yu DY, Lee GM, Appl. Microbiol. Biotechnol., 92, 779 (2011)
- Noh SM, Park JH, Lim MS, Kim JW, Lee GM, Appl. Microbiol. Biotechnol., 101, 1035 (2017)
- Irani N, Wirth M, Heuvel JVD, Wagner R, Biotechnol. Bioeng., 66, 238 (1999)
- Vallee C, Durocher Y, Henry O, J. Biotechnol., 169, 63 (2014)
- Toussaint C, Henry O, Durocher Y, J. Biotechnol., 217, 122 (2016)
- Gupta SK, Srivastava SK, Sharma A, Nalage VHH, Salvi D, Kushwaha H, Chitnis NB, Shukla P, PLoS One, 12, e0181455 (2017)
- Gupta SK, Sharma A, Kushwaha H, Shukla P, Front. Pharmacol., 8, 463 (2017)
- Wlaschin KF, Hu WS, J. Biotechnol., 131, 168 (2007)
- 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)
- Wilkens CA, Altamirano C, Gerdtzen ZP, Biotechnol. Bioprocess Eng., 16, 714 (2011)
- Torres M, Berrios J, Rigual Y, Latorre Y, Vergara M, Dickson AJ, Altamirano C, Chem. Eng. Sci., 205, 201 (2019)
- Buchsteiner M, Quek LE, Gray P, Nielsen LK, Biotechnol. Bioeng., 115, 2315 (2018)
- Moller J, Bhat K, Guhl L, Portner R, Jandt U, Zeng AP, Eng. Life Sci., 21, 100 (2021)
- Urquiza LT, Martin AEA, James DC, Nagy T, Falconer RJ, Biotechnol. Prog., 36, e2940 (2020)
- Scorrano L, De Matteis MA, Emr S, Giordano F, Hajnóczky G, Kornmann B, Lackner LL, Levine TP, Pellegrini L, Reinisch K, Nat. Commun., 10, 1287 (2019)
- Calleja LL, Lecina M, Repullo JL, Albiol J, Sola C, Cairo JJ, Appl. Microbiol. Biotechnol., 99, 9951 (2015)
- Zalai D, Koczka K, Parta L, Wechselberger P, Klein T, Herwig C, Biotechnol. Prog., 31, 1657 (2015)
- Osman JBJJ, Varley J, Biotechnol. Bioeng., 79, 398 (2002)
- Brunner M, Doppler P, Klein T, Herwig C, Fricke J, Eng. Life Sci., 18, 204 (2018)
- Gagnon M, Hiller G, Luan YT, Kittredge A, DeFelice J, Drapeau D, Biotechnol. Bioeng., 108, 1328 (2011)
- 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)