Galactose Feeding in CHO Cell Culture Process：the Impacts on the Cell Growth,Metabolism and Glycosylation of Fc Fusion Protein

doi:10.13560/j.cnki.biotech.bull.1985.2019-0138

Abstract

Abstract: This work aims to get insights into the effects of feeding galactose on the CHO cell growth,metabolism and product expression during fed-batch culture process. Through substituting glucose with equimolar galactose in the feed medium of CHO cell culture process,the impacts of feeding galactose with varied ratio on cell growth,metabolism and product characteristics of Fc fusion protein were investigated. Results showed that the data from shake flask indicated more than 60% galactose substitution adversely affected cell growth,and the pH of late culture process increased significantly. Moreover,with the increase of galactose substitution proportion in the feed medium,metabolic by-product lactate concentration rapidly decreased,while accumulation of ammonia increased significantly;in addition,the concentrations of glutamic acid and alanine also showed a gradient increase. Within low substitution percentage（0%-40%）of galactose,the titer and sialic acid content increased with the increase of substitution proportion;however,within a higher proportion（60%-100%）,they both decreased with the replacement ratio increasing. Through stably controlling the culture pH in the bioreactor,by replacing the 40% of total glucose with galactose,the titer and total sialic acid content of Fc fusion protein were enhanced by 43% and 37% respectively. In sum,substitution of glucose with galactose in CHO fed-batch process may greatly enhance product expression and sialic acid content,and is conducive to establish the high-yield and high-quality CHO culture process.

Key words: galactose, cell metabolism, glycosylation, Fc fusion protein

XIAO Zheng, FAN Li, TAN Wen-song. Galactose Feeding in CHO Cell Culture Process：the Impacts on the Cell Growth,Metabolism and Glycosylation of Fc Fusion Protein[J]. Biotechnology Bulletin, 2019, 35(8): 138-145.

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