A Markov chain model for N-linked protein glycosylation - towards a low-parameter tool for model-driven glycoengineering.

TitleA Markov chain model for N-linked protein glycosylation - towards a low-parameter tool for model-driven glycoengineering.
Publication TypeJournal Article
Year of Publication2015
AuthorsSpahn PN, Hansen AH, Hansen HG, Arnsdorf J, Kildegaard HF, Lewis NE
JournalMetab Eng
PubMed Date10/2015
ISSN1096-7184
Abstract

Glycosylation is a critical quality attribute of most recombinant biotherapeutics. Consequently, drug development requires careful control of glycoforms to meet bioactivity and biosafety requirements. However, glycoengineering can be extraordinarily difficult given the complex reaction networks underlying glycosylation and the vast number of different glycans that can be synthesized in a host cell. Computational modeling offers an intriguing option to rationally guide glycoengineering, but the high parametric demands of current modeling approaches pose challenges to their application. Here we present a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling. The model recapitulates the biological complexity of glycosylation, but does not require user-provided kinetic information. We use this method to predict and experimentally validate glycoprofiles on EPO, IgG as well as the endogenous secretome following glycosyltransferase knock-out in different Chinese hamster ovary (CHO) cell lines. Our approach offers a flexible and user-friendly platform that can serve as a basis for powerful computational engineering efforts in mammalian cell factories for biopharmaceutical production.

Alternate JournalMetab. Eng.
PubMed ID26537759
Cover Image: 

Location

Location

417 Powell-Focht Bioengineering Hall

9500 Gilman Drive La Jolla, CA 92093-0412

Contact Us

Contact Us

In Silico Lab:  858-822-1144

Wet Lab:  858-246-1625

FAX:   858-822-3120

Website Concerns: sbrgit@ucsd.edu

User Login