caa a22 4500 605499594 CHVBK 20210128100551.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00253-015-6789-5 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6789-5 Understanding the intracellular effects of yeast extract on the enhancement of Fc-fusion protein production in Chinese hamster ovary cell culture [Elektronische Daten] [Dongdong Hu, Yating Sun, Xuping Liu, Jintao Liu, Xintao Zhang, Liang Zhao, Haibin Wang, Wen-Song Tan, Li Fan] 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. Springer-Verlag Berlin Heidelberg, 2015 Chinese hamster ovary cells nationallicence Yeast extract nationallicence Fc-fusion protein nationallicence Specific productivity nationallicence Cell cycle arrest nationallicence mTOR nationallicence Hu Dongdong 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 aut Sun Yating 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 aut Liu Xuping 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 aut Liu Jintao 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 aut Zhang Xintao 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 aut Zhao Liang 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 aut Wang Haibin Zhejiang Hisun Pharmaceutical Co., Ltd., Fuyang, 311404, Hangzhou, Zhejiang, China aut Tan Wen-Song 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 aut Fan Li 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 aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8429-8440 0175-7598 99:20<8429 2015 99 253 https://doi.org/10.1007/s00253-015-6789-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6789-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hu Dongdong 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 aut NATIONALLICENCE 700 1- Sun Yating 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 aut NATIONALLICENCE 700 1- Liu Xuping 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 aut NATIONALLICENCE 700 1- Liu Jintao 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 aut NATIONALLICENCE 700 1- Zhang Xintao 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 aut NATIONALLICENCE 700 1- Zhao Liang 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 aut NATIONALLICENCE 700 1- Wang Haibin Zhejiang Hisun Pharmaceutical Co., Ltd., Fuyang, 311404, Hangzhou, Zhejiang, China aut NATIONALLICENCE 700 1- Tan Wen-Song 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 aut NATIONALLICENCE 700 1- Fan Li 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 aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8429-8440 0175-7598 99:20<8429 2015 99 253