Remodeling of the Glycosylation Pathway in the Methylotrophic Yeast Hansenula polymorpha to Produce Human Hybrid-Type N-Glycans

Seon Ah Cheon; Hyunah Kim; Doo-Byoung Oh; Ohsuk Kwon; Hyun Ah Kang

doi:10.1007/s12275-012-2097-2

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Research Support, Non-U.S. Gov't
Remodeling of the Glycosylation Pathway in the Methylotrophic Yeast Hansenula polymorpha to Produce Human Hybrid-Type N-Glycans: Seon Ah Cheon ^1,2, Hyunah Kim ³, Doo-Byoung Oh ², Ohsuk Kwon ², Hyun Ah Kang ^1,3; Journal of Microbiology 2012;50(2):341-348.
DOI: https://doi.org/10.1007/s12275-012-2097-2
Published online: April 27, 2012

¹Research Center for Biomolecules and Biosystems, College of Natural Science, Chung-Ang University, Seoul 156-756, Republic of Korea, ²Systems and Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea, ³Department of Life Science, College of Natural Science, Chung-Ang University, Seoul 156-756, Republic of Korea

Corresponding author: Hyun Ah Kang , Tel: +82-2-820-5863,

Received: 22 February 2012 • Accepted: 13 March 2012

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Abstract

As a step forward to achieve the generation of human complex- type N-glycans in the methylotrophic yeast Hansenula polymorpha, we here report the modification of the yeast glycosylation pathway by heterologous expression of the human gene encoding β-1,2-N-acetylglucosaminyltransferase I (GnTI). For the optimal expression of human GnTI in the yeast Golgi compartment, the catalytic domain of the GnTI was fused to various N-terminal leader sequences derived from the yeast type II membrane proteins. The vectors containing GnTI fusion constructs were introduced into the H. polymorpha och1Δ single and och1Δalg3Δ double mutant strains expressing the ER-targeted Aspergillus saitoi α-1,2 mannosidase, respectively. Both of the glycoengineered Hpoch1Δ and Hpoch1ΔHpalg3Δ strains were shown to produce successfully the hybrid-type glycans with a monoantennary N-acetylglucosamine (GlcNAc1Man5GlcNAc2 and GlcNAc1Man3GlcNAc2, respectively) by N-glycan profile analysis of cell wall proteins. Furthermore, by comparative analysis of byproduct formation and the glycosylation site occupancy, we propose that the Hpoch1Δ strain would be more suitable than the Hpoch1ΔHpalg3Δ strain as a host for the production of recombinant proteins with humanized glycans.

Keywords: Hansenula polymorpha;humanized hybrid-type N-glycans;ALG3;OCH1

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Remodeling of the Glycosylation Pathway in the Methylotrophic Yeast Hansenula polymorpha to Produce Human Hybrid-Type N-Glycans

J. Microbiol. 2012;50(2):341-348. Published online April 27, 2012

DOI: https://doi.org/10.1007/s12275-012-2097-2

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