Understanding the intracellular effects of yeast extract on the enhancement of Fc-fusion protein production in Chinese hamster ovary cell culture

Verfasser / Beitragende:
[Dongdong Hu, Yating Sun, Xuping Liu, Jintao Liu, Xintao Zhang, Liang Zhao, Haibin Wang, Wen-Song Tan, Li Fan]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/20(2015-10-01), 8429-8440
Format:
Artikel (online)
ID: 605499594
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024 7 0 |a 10.1007/s00253-015-6789-5  |2 doi 
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245 0 0 |a Understanding the intracellular effects of yeast extract on the enhancement of Fc-fusion protein production in Chinese hamster ovary cell culture  |h [Elektronische Daten]  |c [Dongdong Hu, Yating Sun, Xuping Liu, Jintao Liu, Xintao Zhang, Liang Zhao, Haibin Wang, Wen-Song Tan, Li Fan] 
520 3 |a Yeast extract (YE), as a non-animal source additive for mammalian cell culture medium, has been widely used for manufacturing of therapeutic proteins. In the present study, one particular YE was found to have significantly improved the specific productivity (q p) of Fc-fusion protein in recombinant Chinese hamster ovary (rCHO) cell culture. In order to elucidate the intracellular effects of YE on protein productivity, steps of the target protein synthesis process were investigated to unveil their variations caused by YE addition. Stepwise analysis on Fc-fusion protein synthesis process showed that YE enhanced Fc-fusion protein gene transcription with cell cycle arrest at G1 phase; mammalian target of rapamycin (mTOR) signaling pathway was activated to enhance the translation of Fc-fusion protein, and the block in post-translational steps of Fc-fusion protein was alleviated by YE addition as well. Our results revealed the responses of multiple protein production steps to the addition of YE and provided a practical guidance for the separation and application of active compounds from hydrolysates. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Chinese hamster ovary cells  |2 nationallicence 
690 7 |a Yeast extract  |2 nationallicence 
690 7 |a Fc-fusion protein  |2 nationallicence 
690 7 |a Specific productivity  |2 nationallicence 
690 7 |a Cell cycle arrest  |2 nationallicence 
690 7 |a mTOR  |2 nationallicence 
700 1 |a Hu  |D Dongdong  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
700 1 |a Sun  |D Yating  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
700 1 |a Liu  |D Xuping  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
700 1 |a Liu  |D Jintao  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
700 1 |a Zhang  |D Xintao  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
700 1 |a Zhao  |D Liang  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
700 1 |a Wang  |D Haibin  |u Zhejiang Hisun Pharmaceutical Co., Ltd., Fuyang, 311404, Hangzhou, Zhejiang, China  |4 aut 
700 1 |a Tan  |D Wen-Song  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
700 1 |a Fan  |D Li  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/20(2015-10-01), 8429-8440  |x 0175-7598  |q 99:20<8429  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6789-5  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6789-5  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hu  |D Dongdong  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sun  |D Yating  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Liu  |D Xuping  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Liu  |D Jintao  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Xintao  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhao  |D Liang  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Haibin  |u Zhejiang Hisun Pharmaceutical Co., Ltd., Fuyang, 311404, Hangzhou, Zhejiang, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tan  |D Wen-Song  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fan  |D Li  |u State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309, 200237, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/20(2015-10-01), 8429-8440  |x 0175-7598  |q 99:20<8429  |1 2015  |2 99  |o 253