Expression of natural human [beta]1,4-GalT1 variants and of non-mammalian homologues in plants leads to differences in galactosylation of N-glycans

[beta]1,4-Galactosylation of plant N-glycans is a prerequisite for commercial production of certain biopharmaceuticals in plants. Two different types of galactosylated N-glycans have initially been reported in plants as the result of expression of human [beta]1,4-galactosyltransferase 1 (GalT). Here...

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Bibliographic Details
Published in:Transgenic research 2014-10, Vol.23 (5), p.717
Main Authors: Hesselink, Thamara, Rouwendal, Gerard J, A, Henquet, Maurice G, L, Florack, Dion E, Helsper, Johannes P, F, G, Bosch, Dirk
Format: Article
Language:English
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Summary:[beta]1,4-Galactosylation of plant N-glycans is a prerequisite for commercial production of certain biopharmaceuticals in plants. Two different types of galactosylated N-glycans have initially been reported in plants as the result of expression of human [beta]1,4-galactosyltransferase 1 (GalT). Here we show that these differences are associated with differences at its N-terminus: the natural short variant of human GalT results in hybrid type N-glycans, whereas the long form generates bi-antennary complex type N-glycans. Furthermore, expression of non-mammalian, chicken and zebrafish GalT homologues with N-termini resembling the short human GalT N-terminus also induce hybrid type N-glycans. Providing both non-mammalian GalTs with a 13 amino acid N-terminal extension that distinguishes the two naturally occurring forms of human GalT, acted to increase the levels of bi-antennary galactosylated N-glycans when expressed in tobacco leaves. Replacement of the cytosolic tail and transmembrane domain of chicken and zebrafish GalTs with the corresponding region of rat [alpha]2,6-sialyltransferase yielded a gene whose expression enhanced the level of bi-antennary galactosylation even further.[PUBLICATION ABSTRACT]
ISSN:0962-8819
1573-9368
DOI:10.1007/s11248-014-9806-z