Recent Developments in Deciphering the Biological Role of Plant Complex N-Glycans

Strasser, Richard

doi:10.3389/fpls.2022.897549

Cited by 9 publications

(10 citation statements)

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“…GNTI is a key enzyme of the N-glycan processing pathway as it initiates the formation of complex N-glycans ( von Schaewen et al., 1993 ; Schachter, 2000 ), and GNTI deficiency leads to severe phenotypes in plants ( Strasser, 2022 ). The tobacco GNTI protein is well characterized, and specific roles have been assigned to the cytoplasmic tail ( Schoberer et al., 2009 ), the transmembrane domain ( Schoberer et al., 2019 ), and the stem region ( Schoberer et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…The attached N-glycans subsequently undergo trimming and processing from mannosidic-type ones to complex-type ones. The complex N-glycans are generated in the Golgi apparatus, and distinct modifications on these N-glycans contribute to specific functions of the glycoproteins ( Strasser, 2022 ). N-acetylglucosaminyltransferase I (GNTI or MGAT1) is one of the key processing enzymes in the cis /medial Golgi, as it initiates the formation of hybrid-type and complex N-glycans by transferring a single GlcNAc residue to Man 5 GlcNAc 2 ( Strasser et al., 1999a ).…”

Section: Introductionmentioning

confidence: 99%

“…Oryza sativa and Lotus japonicas GNTI knockout mutants display severe growth defects and problems with reproduction ( Fanata et al., 2013 ; Pedersen et al., 2017 ). Arabidopsis thaliana GNTI-deficient plants are more sensitive to salt stress and show alterations in root hair development ( Kang et al., 2008 ; Frank et al., 2021 ; Strasser, 2022 ). Together, these examples highlight the importance of GNTI function for different multicellular organisms, including plants.…”

Section: Introductionmentioning

confidence: 99%

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The tobacco GNTI stem region harbors a strong motif for homomeric protein complex formation

Schoberer,

Izadi,

Kierein

et al. 2023

Front. Plant Sci.

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IntroductionThe Golgi apparatus of plants is the central cellular organelle for glycan processing and polysaccharide biosynthesis. These essential processes are catalyzed by a large number of Golgi-resident glycosyltransferases and glycosidases whose organization within the Golgi is still poorly understood.MethodsHere, we examined the role of the stem region of the cis/medial Golgi enzyme N-acetylglucosaminyltransferase I (GNTI) in homomeric complex formation in the Golgi of Nicotiana benthamiana using biochemical approaches and confocal microscopy.ResultsTransient expression of the N-terminal cytoplasmic, transmembrane, and stem (CTS) regions of GNTI leads to a block in N-glycan processing on a co-expressed recombinant glycoprotein. Overexpression of the CTS region from Golgi α-mannosidase I, which can form in planta complexes with GNTI, results in a similar block in N-glycan processing, while GNTI with altered subcellular localization or N-glycan processing enzymes located further downstream in the Golgi did not affect complex N-glycan processing. The GNTI-CTS-dependent alteration in N-glycan processing is caused by a specific nine-amino acid sequence motif in the stem that is required for efficient GNTI-GNTI interaction.DiscussionTaken together, we have identified a conserved motif in the stem region of the key N-glycan processing enzyme GNTI. We propose that the identified sequence motif in the GNTI stem region acts as a dominant negative motif that can be used in transient glycoengineering approaches to produce recombinant glycoproteins with predominantly mannosidic N-glycans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The tobacco GNTI stem region harbors a strong motif for homomeric protein complex formation

Schoberer,

Izadi,

Kierein

et al. 2023

Front. Plant Sci.

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“…A complex metabolic network and many glycosylation pathways are used during the enzymatic glycosylation of proteins to produce a wide variety of proteoforms ( Schjoldager et al., 2020 ). For instance in humans, N-acetylglucosaminyl transferases IV and V present in Golgi functions in galactosylation, branch elongation and sialic acid capping, which is not found in plants ( Strasser, 2022 ; Strasser, 2023 ). In order to produce therapeutic proteins of interest in plant with desired glycosylation pattern, β-1,4 galactosyl transferase co-expression and sub-cellular localization to Golgi is preferred ( Navarre et al., 2017 ; Strasser, 2022 ).…”

Section: Systems Engineering Approaches To Produce Recombinant Biopha...mentioning

confidence: 99%

Artificial intelligence-driven systems engineering for next-generation plant-derived biopharmaceuticals

Parthiban,

Vijeesh,

Gayathri

et al. 2023

Front. Plant Sci.

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Recombinant biopharmaceuticals including antigens, antibodies, hormones, cytokines, single-chain variable fragments, and peptides have been used as vaccines, diagnostics and therapeutics. Plant molecular pharming is a robust platform that uses plants as an expression system to produce simple and complex recombinant biopharmaceuticals on a large scale. Plant system has several advantages over other host systems such as humanized expression, glycosylation, scalability, reduced risk of human or animal pathogenic contaminants, rapid and cost-effective production. Despite many advantages, the expression of recombinant proteins in plant system is hindered by some factors such as non-human post-translational modifications, protein misfolding, conformation changes and instability. Artificial intelligence (AI) plays a vital role in various fields of biotechnology and in the aspect of plant molecular pharming, a significant increase in yield and stability can be achieved with the intervention of AI-based multi-approach to overcome the hindrance factors. Current limitations of plant-based recombinant biopharmaceutical production can be circumvented with the aid of synthetic biology tools and AI algorithms in plant-based glycan engineering for protein folding, stability, viability, catalytic activity and organelle targeting. The AI models, including but not limited to, neural network, support vector machines, linear regression, Gaussian process and regressor ensemble, work by predicting the training and experimental data sets to design and validate the protein structures thereby optimizing properties such as thermostability, catalytic activity, antibody affinity, and protein folding. This review focuses on, integrating systems engineering approaches and AI-based machine learning and deep learning algorithms in protein engineering and host engineering to augment protein production in plant systems to meet the ever-expanding therapeutics market.

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“…l -fucose (6-deoxy- l -galactose) is ubiquitously found in mammals, plants, insects and microbes as part of oligosaccharides, glycoproteins such as mucins, or lipid forming glycoconjugates via α linkage [ 1 ], whilst β- l -fucose is rare and only seldomly reported in bacteria [ 2 ]. These structures are involved in a myriad of physiological processes, including immune recognition [ 3 ], development and neural functions [ 4 , 5 ] plant immunity [ 6 , 7 ] or host-microbe interactions (for a review see [ 8 ]). For example, Fuc has been implicated in bacteria colonisation by modulating chemotaxis [ 9 ], swimming motility [ 10 ], pathogenesis [ 11 ] or by acting as nutrient source for commensal or pathogenic bacteria [ 12–14 ].…”

Section: Introductionmentioning

confidence: 99%

Structure and function of microbial α-l-fucosidases: a mini review

Owen

Juge

2023

Essays in Biochemistry

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Fucose is a monosaccharide commonly found in mammalian, insect, microbial and plant glycans. The removal of terminal α-l-fucosyl residues from oligosaccharides and glycoconjugates is catalysed by α-l-fucosidases. To date, glycoside hydrolases (GHs) with exo-fucosidase activity on α-l-fucosylated substrates (EC 3.2.1.51, EC 3.2.1.-) have been reported in the GH29, GH95, GH139, GH141 and GH151 families of the Carbohydrate Active Enzymes (CAZy) database. Microbes generally encode several fucosidases in their genomes, often from more than one GH family, reflecting the high diversity of naturally occuring fucosylated structures they encounter. Functionally characterised microbial α-l-fucosidases have been shown to act on a range of substrates with α-1,2, α-1,3, α-1,4 or α-1,6 fucosylated linkages depending on the GH family and microorganism. Fucosidases show a modular organisation with catalytic domains of GH29 and GH151 displaying a (β/α)8-barrel fold while GH95 and GH141 show a (α/α)6 barrel and parallel β-helix fold, respectively. A number of crystal structures have been solved in complex with ligands, providing structural basis for their substrate specificity. Fucosidases can also be used in transglycosylation reactions to synthesise oligosaccharides. This mini review provides an overview of the enzymatic and structural properties of microbial α-l-fucosidases and some insights into their biological function and biotechnological applications.

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Recent Developments in Deciphering the Biological Role of Plant Complex N-Glycans

Cited by 9 publications

References 62 publications

The tobacco GNTI stem region harbors a strong motif for homomeric protein complex formation

The tobacco GNTI stem region harbors a strong motif for homomeric protein complex formation

Artificial intelligence-driven systems engineering for next-generation plant-derived biopharmaceuticals

Structure and function of microbial α-l-fucosidases: a mini review

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