상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Glycoengineering of the methylotrophic yeast Hansenula polymorpha for the production of glycoproteins with trimannosyl core N-glycan by blocking core oligosaccharide assembly

Authors 

Doo-Byoung OhJ S ParkMoo Woong KimSeon Ah CheonEun Jung KimHye Yun MoonOh Suk KwonSang Ki RheeHyun Ah Kang

Publisher 

Wiley-Blackwell

Issue Date 

2008

Citation 

Biotechnology Journal, vol. 3, no. 5, pp. 659-668

Keywords 

ALG3glycoengineeringhansenula polymorphatrimannosyl core N-glycanoligosaccharidesproteinssynthesis (chemical)yeastbiotechnology

Abstract 

The initial lipid-linked oligosaccharide Glc3Man9GlcNAc2-dolichyl pyrophosphate (Dol-PP) for N-glycan is synthesized and assembled at the membrane of the endoplasmic reticulum (ER) and subsequently transferred to a nascent polypeptide by the oligosaccharide transferase complex. We have identified an ALG3 homolog (HpALG3) coding for a dolichyl-phosphate-mannose dependent α-1,3-mannosyltransferase in the methylotrophic yeast Hansenula polymorpha. The detailed analysis of glycan structure by linkage-specific mannosidase digestion showed that HpALG3 is responsible for the conversion of MAn5GlcNAc2-Dol-PP to Man6GlcNAc2-Dol-PP, the first step to attach a mannose to the lipid-linked oligosaccharide in the ER. The N-glycosylation pathway of H. polymorpha has been remodeled by deleting the HpALG3 gene in the Hpoch1 null mutant strain blocked in the yeast-specific outer mannose chain synthesis and by introducing an ER-targeted Aspergillus saitoi α-1,2-mannosidase gene. This glycoengineered H. polymorpha strain produced glycoproteins mainly containing trimannosyl core N-glycan (Man3GlcNAc2), which is the common core backbone of various human-type N-glycans. The results demonstrate the high potential of H. polymorpha to be developed as an efficient expression system for the production of glycoproteins with humanized glycans.

ISSN 

1860-6768

Link 

http://dx.doi.org/10.1002/biot.200700252

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)