Journal
JOURNAL OF BIOTECHNOLOGY
Volume 186, Issue -, Pages 110-118Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jbiotec.2014.06.026
Keywords
Tyrosine solubility; Fed-batch; Monoclonal antibody; Productivity; Single feed
Categories
Ask authors/readers for more resources
Fed-batch culture bioprocesses are currently used predominantly for the production of recombinant proteins, especially monoclonal antibodies. In these cultures, concentrated feeds are added during cultivation to prevent nutrient depletion, thus extending the cellular growth phase and increasing product concentrations. One limitation in these bioprocesses arises from the low solubility or stability of some compounds at high concentrations, in particular amino acids. This study describes the synthesis and evaluation of a phosphotyrosine disodium salt as a tyrosine source in fed-batch processes. This molecule is highly soluble in concentrated feeds at neutral pH. Mechanistic studies demonstrated that the molecule is cleaved in the cell culture supernatant after processing by released phosphatases, leading to phosphate and free L-tyrosine which can be taken up by the cells. No intact phosphotyrosine was detected intra-cellularly or incorporated into the sequence of the monoclonal antibody. The use of this new molecule allows the simplification of fed-batch processes in large scale manufacturing via the implementation of neutral pH, highly concentrated feeds. (C) 2014 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available