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ACS Synthetic Biology Jul 2020Protein glycosylation, the attachment of sugars to amino acid side chains, can endow proteins with a wide variety of properties of great interest to the engineering... (Review)
Review
Protein glycosylation, the attachment of sugars to amino acid side chains, can endow proteins with a wide variety of properties of great interest to the engineering biology community. However, natural glycosylation systems are limited in the diversity of glycoproteins they can synthesize, the scale at which they can be harnessed for biotechnology, and the homogeneity of glycoprotein structures they can produce. Here we provide an overview of the emerging field of synthetic glycobiology, the application of synthetic biology tools and design principles to better understand and engineer glycosylation. Specifically, we focus on how the biosynthetic and analytical tools of synthetic biology have been used to redesign glycosylation systems to obtain defined glycosylation structures on proteins for diverse applications in medicine, materials, and diagnostics. We review the key biological parts available to synthetic biologists interested in engineering glycoproteins to solve compelling problems in glycoscience, describe recent efforts to construct synthetic glycoprotein synthesis systems, and outline exemplary applications as well as new opportunities in this emerging space.
Topics: Animals; Bacteria; Biotechnology; Fungi; Glycosylation; Glycosyltransferases; Plants; Proteins; Synthetic Biology
PubMed: 32526139
DOI: 10.1021/acssynbio.0c00210 -
Advances in Experimental Medicine and... 2021Although changes in protein glycosylation are observed in a wide range of diseases and pathological states, the examples of use of glycans as biomarkers and therapeutic... (Review)
Review
Although changes in protein glycosylation are observed in a wide range of diseases and pathological states, the examples of use of glycans as biomarkers and therapeutic targets are limited. This is not in small part because the understanding of human glycome regulation in vivo is incomplete and fragmented. Combination of human glycomics and genomics offers a powerful "data-driven hypotheses" approach to dissect the complex human glycobiology in vivo in an agnostic manner.In this chapter we review a decade of quantitative genetic studies of human N-glycome, including studies of its heritability and gene-mapping via genome-wide association studies (GWASs). We show that GWASs of human N-glycome start revealing regulators of the biochemical network of N-glycosylation. Some of these regulators demonstrate pleiotropic effects on human disease, especially autoimmune and inflammatory. We emphasize the use of in silico functional methods and multi-omics approaches to prioritize functional mechanisms to be further validated in laboratory experiments. This combined approach will lead to better understanding of mechanisms of regulation of human protein glycosylation and will provide a rich source of etiologic insight, therapeutic interventions, and biomarkers.
Topics: Genome-Wide Association Study; Genomics; Glycomics; Glycosylation; Humans; Polysaccharides
PubMed: 34495534
DOI: 10.1007/978-3-030-70115-4_7 -
Glycoconjugate Journal Jun 2023After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function.... (Review)
Review
After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function. These events include inter-cell communication, cell proliferation, cell migration, extracellular matrix differentiation, and other critical biological processes. Glycosylation is the crucial conservative and universal post-translational modification in all eukaryotic cells [1], with influential roles in intercellular recognition, regulation, signaling, immune response, cellular transformation, and disease development. Studies have shown that abnormally glycosylation of proteins is a well-recognized feature of cancer cells, and specific glycan structures are considered markers of tumor development. There are many studies on gene expression and regulation during tissue repair and regeneration. Still, there needs to be more knowledge of complex carbohydrates' effects on tissue repair and regeneration, such as glycosylation. Here, we present a review of studies investigating protein glycosylation in the tissue repair and regeneration process.
Topics: Glycosylation; Wound Healing; Carbohydrates; Polysaccharides; Protein Processing, Post-Translational
PubMed: 37097318
DOI: 10.1007/s10719-023-10117-8 -
Klinicka Onkologie : Casopis Ceske a... 2022Glycosylation is a posttranslational modification responsible for many bio-logical processes including protein-protein interactions, cell signaling or cell cycle... (Review)
Review
BACKGROUND
Glycosylation is a posttranslational modification responsible for many bio-logical processes including protein-protein interactions, cell signaling or cell cycle regulation. Changes in glycosylation of serum proteins reflects the status of tissues and cells in the organism and therefore can be used as markers for dia-gnosis of cancer, its progression and determination of its subtypes. N-glycan profiling is often used for characterization of N-glycosylation changes. It is based on the measurements of N-glycans released from the serum proteins. Beside the N-glycan profiling, glycoproteomic approach is emerging as it preserves the information about glycan composition, original protein, and its glycosylation sites.
PURPOSE
This review covers existing works describing the changes in serum protein N-glycosylation in various cancer types. Attention was paid to both the glycomic and glycoproteomic approaches. The last part of the review shortly presents the analytical methods used for these analyses.
Topics: Blood Proteins; Glycomics; Glycosylation; Humans; Neoplasms; Polysaccharides
PubMed: 35760569
DOI: 10.48095/ccko2022174 -
Insect Biochemistry and Molecular... Apr 2017The majority of proteins is modified with carbohydrate structures. This modification, called glycosylation, was shown to be crucial for protein folding, stability and... (Review)
Review
The majority of proteins is modified with carbohydrate structures. This modification, called glycosylation, was shown to be crucial for protein folding, stability and subcellular location, as well as protein-protein interactions, recognition and signaling. Protein glycosylation is involved in multiple physiological processes, including embryonic development, growth, circadian rhythms, cell attachment as well as maintenance of organ structure, immunity and fertility. Although the general principles of glycosylation are similar among eukaryotic organisms, insects synthesize a distinct repertoire of glycan structures compared to plants and vertebrates. Consequently, a number of unique insect glycans mediate functions specific to this class of invertebrates. For instance, the core α1,3-fucosylation of N-glycans is absent in vertebrates, while in insects this modification is crucial for the development of wings and the nervous system. At present, most of the data on insect glycobiology comes from research in Drosophila. Yet, progressively more information on the glycan structures and the importance of glycosylation in other insects like beetles, caterpillars, aphids and bees is becoming available. This review gives a summary of the current knowledge and recent progress related to glycan diversity and function(s) of protein glycosylation in insects. We focus on N- and O-glycosylation, their synthesis, physiological role(s), as well as the molecular and biochemical basis of these processes.
Topics: Animals; Carbohydrate Metabolism; Glycosylation; Insect Proteins; Insecta
PubMed: 28232040
DOI: 10.1016/j.ibmb.2017.02.005 -
Biology of Reproduction Dec 2023Infertility is a challenging health problem that affects 8-15% of couples worldwide. Establishing pregnancy requires successful embryo implantation, but about 85% of... (Review)
Review
Infertility is a challenging health problem that affects 8-15% of couples worldwide. Establishing pregnancy requires successful embryo implantation, but about 85% of unsuccessful pregnancies are due to embryo implantation failure or loss soon after. Factors crucial for successful implantation include invasive blastocysts, receptive endometrium, invasion of trophoblast cells, and regulation of immune tolerance at the maternal-fetal interface. Maternal-fetal crosstalk, which relies heavily on protein-protein interactions, is a critical factor in implantation that involves multiple cellular communication and molecular pathways. Glycosylation, a protein modification process, is closely related to cell growth, adhesion, transport, signal transduction, and recognition. Protein glycosylation plays a crucial role in maternal-fetal crosstalk and can be divided into N-glycosylation and O-glycosylation, which are often terminated by sialylation or fucosylation. This review article examines the role of protein glycosylation in maternal-fetal crosstalk based on two transcriptome datasets from the GEO database (GSE139087 and GSE113790) and existing research, particularly in the context of the mechanism of protein glycosylation and embryo implantation. Dysregulation of protein glycosylation can lead to adverse pregnancy outcomes, such as missed abortion and recurrent spontaneous abortion, underscoring the importance of a thorough understanding of protein glycosylation in the diagnosis and treatment of female reproductive disorders. This knowledge could have significant clinical implications, leading to the development of more effective diagnostic and therapeutic approaches for these conditions.
Topics: Pregnancy; Female; Humans; Glycosylation; Embryo Implantation; Endometrium; Pregnancy Outcome; Abortion, Habitual
PubMed: 37658761
DOI: 10.1093/biolre/ioad105 -
Cells May 2021Evading host immune surveillance is one of the hallmarks of cancer. Immune checkpoint therapy, which aims to eliminate cancer progression by reprogramming the antitumor... (Review)
Review
Evading host immune surveillance is one of the hallmarks of cancer. Immune checkpoint therapy, which aims to eliminate cancer progression by reprogramming the antitumor immune response, currently occupies a solid position in the rapidly expanding arsenal of cancer therapy. As most immune checkpoints are membrane glycoproteins, mounting attention is drawn to asking how protein glycosylation affects immune function. The answers to this fundamental question will stimulate the rational development of future cancer diagnostics and therapeutic strategies.
Topics: Animals; Glycosylation; Humans; Immune Checkpoint Inhibitors; Neoplasms; Protein Processing, Post-Translational; Receptors, Immunologic
PubMed: 34064396
DOI: 10.3390/cells10051100 -
Biochemistry Jan 2018Protein glycosylation is one of the most common post-translational modifications and can influence many properties of proteins. Abnormal protein glycosylation can lead... (Review)
Review
Protein glycosylation is one of the most common post-translational modifications and can influence many properties of proteins. Abnormal protein glycosylation can lead to protein malfunction and serious disease. While appreciation of glycosylation's importance is growing in the scientific community, especially in recent years, a lack of homogeneous glycoproteins with well-defined glycan structures has made it difficult to understand the correlation between the structure of glycoproteins and their properties at a quantitative level. This has been a significant limitation on rational applications of glycosylation and on optimizing glycoprotein properties. Through the extraordinary efforts of chemists, it is now feasible to use chemical synthesis to produce collections of homogeneous glycoforms with systematic variations in amino acid sequence, glycosidic linkage, anomeric configuration, and glycan structure. Such a technical advance has greatly facilitated the study and application of protein glycosylation. This Perspective highlights some representative work in this research area, with the goal of inspiring and encouraging more scientists to pursue the glycosciences.
Topics: Amino Acid Sequence; Forecasting; Glycopeptides; Glycoproteins; Glycosylation; Humans; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Mutagenesis, Site-Directed; Polysaccharides; Protein Conformation; Protein Engineering; Protein Processing, Post-Translational; Protein Stability
PubMed: 29309128
DOI: 10.1021/acs.biochem.7b01055 -
International Journal of Biological... Jul 2017Protein crucial function and flexibility directly depend on its whole structure which is determined by the native distribution of structural elements. Any disturbances... (Review)
Review
Protein crucial function and flexibility directly depend on its whole structure which is determined by the native distribution of structural elements. Any disturbances in a protein architecture leads to many kind of abnormalities and intra- or extracellular accumulation of misfolded proteins which are the basis of conformational diseases. Glycation is one of the most important unwanted post-translational modifications (PTM) which modifies protein three dimensional decoration and triggers its abnormalities. In current review, we take a look at the brief history of protein glycation, its mechanism and kinetics, glycation consequences and toxic products and its involvement in protein chemical modification, aggregation amyloids and fibril formation and different mechanisms induced by such alterations.
Topics: Animals; Glycosylation; Humans; Kinetics; Protein Aggregates; Proteins
PubMed: 26751401
DOI: 10.1016/j.ijbiomac.2015.12.085 -
Biotechnology Advances Oct 2023In order to meet the rising demand for biologics and become competitive on the developing biosimilar market, there is a need for process intensification of... (Review)
Review
In order to meet the rising demand for biologics and become competitive on the developing biosimilar market, there is a need for process intensification of biomanufacturing processes. Process development of biologics has historically relied on extensive experimentation to develop and optimize biopharmaceutical manufacturing. Experimentation to optimize media formulations, feeding schedules, bioreactor operations and bioreactor scale up is expensive, labor intensive and time consuming. Mathematical modeling frameworks have the potential to enable process intensification while reducing the experimental burden. This review focuses on mathematical modeling of cellular metabolism and N-linked glycosylation as applied to upstream manufacturing of biologics. We review developments in the field of modeling cellular metabolism of mammalian cells using kinetic and stoichiometric modeling frameworks along with their applications to simulate, optimize and improve mechanistic understanding of the process. Interest in modeling N-linked glycosylation has led to the creation of various types of parametric and non-parametric models. Most published studies on mammalian cell metabolism have performed experiments in shake flasks where the pH and dissolved oxygen cannot be controlled. Efforts to understand and model the effect of bioreactor-specific parameters such as pH, dissolved oxygen, temperature, and bioreactor heterogeneity are critically reviewed. Most modeling efforts have focused on the Chinese Hamster Ovary (CHO) cells, which are most commonly used to produce monoclonal antibodies (mAbs). However, these modeling approaches can be generalized and applied to any mammalian cell-based manufacturing platform. Current and potential future applications of these models for Vero cell-based vaccine manufacturing, CAR-T cell therapies, and viral vector manufacturing are also discussed. We offer specific recommendations for improving the applicability of these models to industrially relevant processes.
Topics: Cricetinae; Animals; Glycosylation; Cricetulus; CHO Cells; Cell Culture Techniques; Bioreactors; Biological Products
PubMed: 37257729
DOI: 10.1016/j.biotechadv.2023.108179