Fungi short-chain carboxylate transporter: shift from microbe hereditary functional component to metabolic engineering target

2018 ◽  
Vol 102 (11) ◽  
pp. 4653-4662
Author(s):  
Hongwei Guo ◽  
Tianqiu Huang ◽  
Jun Zhao ◽  
Hongwen Chen ◽  
Guo Chen
2018 ◽  
Vol 2 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Qiong Wang ◽  
Michael J. Betenbaugh

As a complex and common post-translational modification, N-linked glycosylation affects a recombinant glycoprotein's biological activity and efficacy. For example, the α1,6-fucosylation significantly affects antibody-dependent cellular cytotoxicity and α2,6-sialylation is critical for antibody anti-inflammatory activity. Terminal sialylation is important for a glycoprotein's circulatory half-life. Chinese hamster ovary (CHO) cells are currently the predominant recombinant protein production platform, and, in this review, the characteristics of CHO glycosylation are summarized. Moreover, recent and current metabolic engineering strategies for tailoring glycoprotein fucosylation and sialylation in CHO cells, intensely investigated in the past decades, are described. One approach for reducing α1,6-fucosylation is through inhibiting fucosyltransferase (FUT8) expression by knockdown and knockout methods. Another approach to modulate fucosylation is through inhibition of multiple genes in the fucosylation biosynthesis pathway or through chemical inhibitors. To modulate antibody sialylation of the fragment crystallizable region, expressions of sialyltransferase and galactotransferase individually or together with amino acid mutations can affect antibody glycoforms and further influence antibody effector functions. The inhibition of sialidase expression and chemical supplementations are also effective and complementary approaches to improve the sialylation levels on recombinant glycoproteins. The engineering of CHO cells or protein sequence to control glycoforms to produce more homogenous glycans is an emerging topic. For modulating the glycosylation metabolic pathways, the interplay of multiple glyco-gene knockouts and knockins and the combination of multiple approaches, including genetic manipulation, protein engineering and chemical supplementation, are detailed in order to achieve specific glycan profiles on recombinant glycoproteins for superior biological function and effectiveness.


1994 ◽  
Vol 92 (4) ◽  
pp. 629-635 ◽  
Author(s):  
Mercedes Gallardo ◽  
Paloma Munoz De Rueda ◽  
Angel Jesus Matilla ◽  
Isabel Maria Sanchez-Calle

1985 ◽  
Vol 4 ◽  
pp. 116-123 ◽  
Author(s):  
P STEHLE ◽  
S ALBERS ◽  
I AMBERGER ◽  
P PFAENDER ◽  
P FURST

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1898-P
Author(s):  
ADELINA I.L. LANE ◽  
SAVANNA N. WENINGER ◽  
FRANK DUCA

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