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KMID : 0380020150300010044
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Korean Journal of Biotechnology and Bioengineering
2015 Volume.30 No. 1 p.44 ~ p.51
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Enhanced Production of Albumin-erythropoietin by Histone Deacetylase Inhibitors in Recombinant CHO Cells
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Kim Su-Jin
Seo Joon-Serk
Choi Sung-Hun
Cha Hyun-Myoung
Lim Jin-Hyuk
Shin Soo-Ah
Shin Yeon-Kyeong
Kim Dong-Il
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Abstract
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Chinese hamster ovary (CHO) cells are the most widely used mammalian host for the commercial production of recombinant proteins. However, they show relatively low yields of recombinant proteins in comparison with microbial cells. Various strategies have been tried to overcome this drawback. The acetyl moieties are attached to the N-terminus of histone by histone acetyltransferase (HAT) while histone deacetylase (HDAC) removes histone-bound acetyl groups. HDAC inhibitor (HDACi), such as sodium butyrate, sodium propionate and valproic acid, can enhance specific productivity of CHO cells. Human albumin-erythropoietin (Alb-EPO) is a novel 105 kDa protein comprising recombinant human EPO fused to human albumin. In this study, we examined the effects of HDACi on the production of Alb-EPO in CHO cells with various concentrations in the range of 0-1 mM. The results showed that sodium butyrate was found to be the best HDACi for enhancing productivity. It enhanced not only the production of Alb-EPO but also the apoptosis of recombinant CHO cells.
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KEYWORD
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Chinese hamster ovary cells, Histone deacetylase inhibitor, Albumin-EPO, Cell death
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