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Glycoengineering in plants for the development of N-glycan structures compatible with biopharmaceuticals

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Abstract

Plants and plant cells are emerging as promising alternatives for biopharmaceutical production with improved safety and efficiency. Plant cells are capable of performing post-translational modifications (PTMs) similar to those of mammalian cells and are safer than mammalian cells with regard to contamination by infectious pathogens, including animal viruses. However, a major obstacle to producing biopharmaceuticals in plants lies in the fact that plant-derived N-glycans include plant-specific sugar residues such as β1,2-xylose and α1,3-fucose attached to a pentasaccharide core (Man3GlcNAc2) as well as β1,3-galactose and α1,4-fucose involved in Lewis a (Lea) epitope formation that can evoke allergic responses in the human body. In addition, sugar residues such as α1,6-fucose, β1,4-galactose and α2,6-sialic acid, which are thought to play important roles in the activity, transport, delivery and half-life of biopharmaceuticals are absent among the N-glycans naturally found in plants. In order to take advantage of plant cells as a system in which to produce biopharmaceuticals development of plants producing N-glycan structures compatible with biopharmaceuticals is necessary. In this article we summarize the current state of biopharmaceutical production using plants as well as what is known about N-glycosylation processes occurring in the endoplasmic reticulum and Golgi apparatus in plants. Finally, we propose and discuss a strategy for and the associated technical barriers of producing customized N-glycans via removal of enzyme genes that add plant-specific sugar residues and introducing enzyme genes that add sugar residues absent in plants.

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Acknowledgments

This work was supported by grants from the Next-Generation BioGreen Program (SSAC, PJ008109), the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy (10048311) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A2001074), Republic of Korea. J.Y. Yoo and K.S. Ko were supported by scholarships from the BK21 program.

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  1. Division of Applied Life Science and PMBBRC, Gyeongsang National University, 501 Jinju-daero, Jinju, 660-701, Korea

    Jae Yong Yoo, Ki Seong Ko, Sang Yeol Lee & Kyun Oh Lee

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Yoo, J.Y., Ko, K.S., Lee, S.Y. et al. Glycoengineering in plants for the development of N-glycan structures compatible with biopharmaceuticals. Plant Biotechnol Rep 8, 357–376 (2014). https://doi.org/10.1007/s11816-014-0328-1

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