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Glyco-Engineering of Plant-Based Expression Systems.

Rainer Fischer^1,2, Tanja Holland^3,4, Markus Sack^3,5

¹Indiana Biosciences Research Institute, Indianapolis, IN, USA. rfischer@indianabiosciences.org.

Advances in Biochemical Engineering/Biotechnology

|August 3, 2018

Summary

Glyco-engineering plant-based systems produces human proteins with altered glycosylation. While removing plant glycans is key, some plant glycans offer therapeutic benefits.

Keywords:

Glycan Glycoprotein Glycotransferase N-linked O-linked Pharmaceutical protein Recombinant protein Transgenic plant Transient expression

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Area of Science:

Biochemistry
Molecular Biology
Biotechnology

Background:

Secreted proteins in eukaryotes undergo glycosylation, with glycan structures varying by species.
Human therapeutic proteins produced in plants often exhibit plant-like glycosylation, impacting stability, function, and immunogenicity.
Plant-derived glycans can differ significantly from human glycans, particularly in sialylation.

Purpose of the Study:

To explore glyco-engineering strategies in plant-based expression systems for producing therapeutic proteins.
To address the challenge of replicating human-like glycosylation in plants, including sialylation.
To investigate the potential benefits of plant-specific glycans on therapeutic proteins.

Main Methods:

Glyco-engineering of plant-based expression systems.
Coordinated expression of multiple human enzymes to achieve human-like glycosylation.
Analysis of glycan structures on plant-produced therapeutic proteins.

Main Results:

Plant-based systems can be engineered to produce human therapeutic proteins with modified glycosylation patterns.
The precise replication of complex human glycans, including sialylation, is achievable through coordinated enzyme expression.
Plant glycans can confer advantages, such as enhanced immunogenicity for vaccines and improved therapeutic protein efficacy.

Conclusions:

Glyco-engineering offers a viable approach to optimize therapeutic protein production in plants.
While removing plant-specific glycans is often desired, their presence can also be beneficial in certain applications.
Further research into both the removal and utilization of plant glycans is warranted for advancing biopharmaceutical development.