Expression of recombinant human erythropoietin having more complex N-glycans in Drosophila S2 cells through hexosaminidase inhibition

BIOT 269

Yeon Kyu Kim, livest@postech.ac.kr1, Kyoung Ro Kim, icejijon@postech.ac.kr1, Young Hwan Kim, yhkim@kbsi.re.kr2, and Hyung Joon Cha, hjcha@postech.ac.kr1. (1) Department of Chemical Engineering, POSTECH (Pohang University of Science and Technology), Pohang, 790-784, South Korea, (2) Proteomics Team, Korea Basic Science Institute, Daejon, 305-333, South Korea
Human proteins often require post-translational modifications for their biological activities. Insect Drosophila melanogaster S2 cell system is a non-lytic expression system for eukaryotic foreign protein production and has a high productivity. We performed successful secreted production of human erythropoietin (hEPO) in stably transfected S2 cell system. However, this system has different N-glycosylation pattern with mammalian cell system. Thus, we tried the modification of their N-glycosylation pathway. A chemical inhibitor for hexosaminidase was applied to the culture because we guessed this enzyme is a main factor of simple N-glycosylation in Drosophila S2 cells. According to MALDI-TOF mass spectrometry or Western blot, purified S2-cells derived proteins hEPO, had a smaller molecular weight than mammalian derived native proteins. These data suggested that S2-cells derived proteins were incompletely glycosylated, so their biological activities in human body could be abnormal. We also analyzed the N-glycan itself with 2D- HPLC. From these data, we found that the proteins produced in Drosophila S2 cells have N-glycans of simple core structures. When 2-ADN was added, the culture profile was not changed and hEPO had a slightly bigger molecular weight than an original one. Its N-glycans were also analyzed by MALDI-TOF MS and the more complex structure that had a terminal N-acetylglucosamine was clearly detected.
 

Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007