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Two types of transglutaminase catalysed reactions: cross-linking of polyamine or lysine to protein glutamine residues, and crosslinking of proteins.
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The transglutaminases (TGase; EC2.3.2.13) (R-glutaminyl-peptide-aminase-gamma-glutamyltransferase) are a family of enzymes that catalyse post-translational modifications in proteins, producing covalent amide bonds between a primary amine group in a polyamine or lysine (amine donor), and a gamma-carboxamide group of the glutamyl residue of some prot...
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... (TGase; EC2.3.2.13) (R-glutaminyl- peptide-aminase--glutamyltransferase) are a family of enzymes that catalyse post-translational modifications in proteins, producing covalent amide bonds between a primary amine group in a polyamine or lysine (amine donor), and a - carboxamide group of the glutamyl residue of some proteins (amine acceptor) see Fig. (1). The results of this activity are as follows: a) modification of the conformation of the pro- tein; and b) other more extensive conformation changes resulting from bonding between the same protein and between different proteins in order to form high molecular weight conjugates. TGases are widely distributed in organisms as different human, bacteria, nematodes, yeasts, algae, plants, and lower vertebrates. This would indicate that these enzymes play a fundamental role in biological processes [1]. A particular feature of the enzyme is that most of TGases require Ca +2 for their catalytic activity. It has been demonstrated that there is a great difference between protein sequence characteristics [2]; as one example, the two TGases cloned in bacteria (Bacillus subtillis and Streptoverticillium sp.) have no homologies with any known family of enzymes or other TGases. Nine TGases have been described in humans that differ in terms of specific substrates and which have revealed a high degree of sequence homology. The best known is human blood coagulation factor XIII (fibrin- stabilizing factor) [3]. Four transglutaminases are also known to be expressed in the human ...
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Metastasis accounts for 90% of the mortality associated with breast cancer. Upregulated expression of members of the lysyl oxidase (LOX) family of secreted copper amine oxidases catalyzes the crosslinking of collagens and elastin in the extracellular matrix. LOXs are linked to the development and metastatic progression of breast cancers. Accordingl...
Citations
... Other common additives utilised by the food industry include microbial transglutaminase (mTG) and, although useful for modifying the functionality of dietary protein, has Fig. 2 Enteric pathogens contribute to structural damage of the intestinal epithelium, either directly via the production of toxins or indirectly by inducing pro-inflammatory IRs in the gut. Such damage promotes the shedding of IECs, particularly during intracellular infection to prevent bacterial dissemination across the monolayer been found to increase intestinal permeability and suppress pathways involved in protection against enteric pathogens (Santos and Torné 2009;Hu et al. 2011;Kieliszek and Misiewicz 2014;Lerner and Benzvi 2021). The fact that TJ protein components, including claudin and occludin, may act as potential substrates for mTG, in addition to the emulsifying properties of this enzyme, provides a possible explanation for its ability to elevate intestinal permeability (Lerner et al. 2017;Lerner and Matthias 2020). ...
The intestinal epithelium acts as the first line of defence against pathogens present in the lumen of the gastrointestinal tract. The epithelium is composed of a single monolayer that includes a variety of cell types, each of which play roles in nutrient and water absorption, antimicrobial defence, and immunomodulation to maintain a homeostatic gut environment. Tight junction (TJ) complexes between adjacent intestinal epithelial cells are responsible for the structural integrity of the gut barrier and controlling the paracellular translocation of luminal contents. The effectiveness of TJs can be impacted by both genetic and environmental factors including microbiota dysbiosis and dietary components. The increased systemic entry of luminal contents has been associated with the development, progression, and/or relapse of autoimmune diseases such as Crohn’s and rheumatoid arthritis. In particular, the extraintestinal spread of luminal microbes possessing components with structural similarity to those of the human host are thought to be involved in the breakdown of immune tolerance towards host components. Here, the structure and function of the intestinal epithelium are discussed as well as the genetic and environmental factors that influence its permeability. There is emphasis on the role of increased intestinal permeability and how the subsequent translocation of luminal contents could be involved in the development and/or exacerbation of autoimmune diseases. This review reinforces how protecting the integrity of the intestinal epithelium and minimising immunological exposure to luminal components, either directly or indirectly, could be a useful strategy in reducing the prevalence and severity of autoimmune diseases.
... In reality and due to new applications, it represents one of the fastest-growing industrial areas. The number of patent applications filed on mTG is fast growing [3,16,21,[25][26][27]. The global mTG market is anticipated to rise at a considerable rate in the next decade. ...
... "Therefore, mTg can enhance the immunogenicity of gluten and should not be used in food products intended for consumption by CD patients" [46]. In fact, the worries and warnings on safe usage of the industrial enzyme exist in multiple publications [9][10][11][12][13][14]25,28,29,43,46,[111][112][113][114]. Notably, in some European countries like Switzerland and Germany, or in Canada, the public was notified of potential public safety concerns, and recommended labeling the enzyme on the final product [115,116]. ...
... Nearly thirty years have passed since mTG appeared in the processed food industry. Its applications are continually expanding, as is its consumption [6][7][8][19][20][21][22][23][24][25][26]. As with many other food additives, there is often the dark side of it, but despite this, the enzyme is categorized as a processing aid and received the GRAS definition, thus escaping labeling and avoiding a more restricted toxic and safety evaluation. ...
Microbial transglutaminase (mTG) is a heavily used food additive and its industrial transamidated complexes usage is rising rapidly. It was classified as a processing aid and was granted the GRAS (generally recognized as safe) definition, thus escaping full and thorough toxic and safety evaluations. Despite the manufacturers claims, mTG or its cross-linked compounds are immunogenic, pathogenic, proinflammatory, allergenic and toxic, and pose a risk to public health. The enzyme is a member of the transglutaminase family and imitates the posttranslational modification of gluten, by the tissue transglutaminase, which is the autoantigen of celiac disease. The deamidated and transamidated gliadin peptides lose their tolerance and induce the gluten enteropathy. Microbial transglutaminase and its complexes increase intestinal permeability, suppresses enteric protective pathways, enhances microbial growth and gliadin peptide’s epithelial uptake and can transcytose intra-enterocytically to face the sub-epithelial immune cells. The present review updates on the potentially detrimental side effects of mTG, aiming to interest the scientific community, induce food regulatory authorities’ debates on its safety, and protect the public from the mTG unwanted effects.
... Finally, this group decomposes to create the isopeptide group, forming a crosslinked system [ Fig. 2(b-iv)]. [46][47][48] Various synthetic peptides or biomacromolecules with glutamine and lysine were tested to fabricate hydrogel with the transglutaminase. [49][50][51]186 For example, in some cases, the cross-linking between each other is achieved with the enzyme using collagen or gelatin, whey protein, casein, and soy protein, which have both residues at the same time. ...
Enzymes play a central role in fundamental biological processes and have been traditionally used to trigger various processes. In recent years, enzymes have been used to tune biomaterial responses and modify the chemical structures at desired sites. These chemical modifications have allowed the fabrication of various hydrogels for tissue engineering and therapeutic applications. This review provides a comprehensive overview of recent advancements in the use of enzymes for hydrogel fabrication. Strategies to enhance the enzyme function and improve biocompatibility are described. In addition, we describe future opportunities and challenges for the production of enzyme-mediated crosslinkable hydrogels.
... The hy drol y sis of the γ -carboxamide group of glu t a mine plays a sub or di nate role and takes place at low lev els or in the ab sence of an ap pro pri ate acyl accep tor ( Folk and Chung, 2006 ). The fact that TGase can act over a wide va ri ety of pro teins makes it a pow er ful tool ca pa ble of mod i fy ing the struc tural prop er ties of var i ous pep tide ma trixes ( Ahhmed et al., 2007 ) with a high po ten tial for ap pli ca tion in dif fer ent fields such as food, bio med ical, cos metic in dus try, etc ( Santos and Torne, 2009 ). ...
A novel transglutaminase (TGase, EC 2.3.2.13) from antarctic Penicillium chrysogenum was partially purified using ammonium sulfate precipitation and anionic exchange chromatography. The final extract had a specific activity of 7.81 mU/mg, purification fold of 7.16, and a yield of 5.02%. The molecular weight was estimated to be 67 kDa by bioinformatic analysis and SDS - PAGE. Maximum TGase activity was observed at pH 8.0 and 30 °C, mesophilic conditions (near 40 °C) resulted in total inactivation. A slight improvement in TGase activity was observed in the presence of Ca 2+ , it increased to 127.78 ± 9.62% at 35 mM but return to normal values at higher concentrations. Additionally, the enzyme activity decreased progressively in the presence of EDTA and STPP suggesting that the enzyme is Ca 2+ dependent but this cofactor is being supplied by the fermented substrate. The partially purified TGase was used as an additive to modify the rheology of a cold - set gelatin gel achieving an in crease in the gel strength and gumminess of 32.25% and 30.50% respectively.
... Our findings will also add to the scientific understanding of TG and contribute to understanding the role of calcium in regulating TG activity. This knowledge may shed light on the development of TG inhibitors that can, for instance, be used in the treatment of human diseases characterised by TG overexpression, such as coeliac disease, Huntington's disease, Alzheimer's disease and fibrosis [39,40]. At present, we are continuing our investigations into this fascinating enzyme and its potential use in the food industry and medicine. ...
Transglutaminases are a family of enzymes that catalyse the crosslinking of proteins by forming covalent bonds between lysine and glutamine residues in various polypeptides. Crosslinking reactions are involved in blood clots, skin formation, embryogenesis and apoptosis. Clinically, these enzymes appear to be implicated in neurodegenerative diseases, tumors and coeliac diseases. Transglutaminases have great potential for use in the food industry because of their ability to cross‐link proteins that are not normally linked. Here, a gene coding for transglutaminase from Atlantic cod was cloned into a bacterial expression vector and used to transform protein expression in a strain of Escherichia coli. The successful expression of recombinant transglutaminase protein from Atlantic cod (AcTG‐1) as a soluble protein upon induction at low temperature was confirmed by sodium dodecyl sulphate–polyacrylamide gel electrophoresis, immunoblotting and mass spectrometry analysis. Biochemical characterisation demonstrated that the transglutaminase was active between 0 and 65°C, but was completely inactivated after 20 min incubation at 70°C. Interestingly the enzyme displayed cold‐adapted features, such as temperature instability combined with high catalytic efficiency at low temperatures (8–16°C). In addition, the enzyme had optimal activity at 50°C, a new feature for a cold‐adapted enzyme. AcTG‐1 was active in the pH range from 6 to 9, with an optimum at pH 8, and required 5 mM calcium for maximum activity. Potential calcium‐binding sites in the enzyme were predictable, making the enzyme an appropriate model for studying structure–function relationships in the calcium‐dependent transglutaminase family. In vitro gel analysis revealed that transglutaminase cross‐linked casein, collagen and gelatin. The binding of fish fillets in the presence of recombinant AcTG‐1 provided further macroscopic proof for the potential application of AcTG‐1 as a biological cross‐linker in the food industry. Once binding occurred, fish fillets withstood further processing such as frying, boiling, freeze/thawing and chilling. The low‐temperature activity and new enzymatic properties of AcTG‐1 appear to offer advantages over commercially available enzymatic glues in the food industry.
... Although the transglutaminase may come from different sources, the mechanism of the reaction is essentially similar. TGase (proteinglutamine γ-glutamyltransferase, EC2.3.2.13) has a specific reaction where this enzyme catalyzes posttranslational modifications of proteins, producing covalent amide bonds between a primary amine group in a polyamine or lysine (mine donor) and γ-carboxiamide groups of the glutamyl residue of some proteins (amine receptor) (Santos and Torne, 2009). Thus, the isopeptide bond of ε-(γ -Glu) lys will be formed by inter-and intramolecular bonding (Ando et al., 1989). ...
Halal is a term that describes substances that are deemed 'pure and clean' which Muslims are allowed to consume according to Islamic law. The industrialization of food processing in the 20 th and 21 st centuries has exposed Muslims community to various ingredients such as blood plasma, transglutaminase and gelatin introduced in meatballs and surimi product. Muslims are facing difficulties to ascertain which products are permitted or not under the Islamic law. Thus, this paper is to give knowledge of non-halal ingredients being introduced in meatballs and surimi products for consumers, researchers and policy makers. Local halal logo issued by Department of Islamic Development Malaysia (JAKIM) is needed to imply that all ingredients used in the food production and processing are Syariah compliance. The scientific evidence to substantiate any claim on Halal issue was developed based on several methods including PCR-based methods with different mitochondria and chromosomal DNA (MtDNA and cDNA) primers, real-time PCR with different probes and DNA binding agent, loop-mediated isothermal amplification (LAMP) with different primers developed, PCR-RFLP, ELISA and etc.
... Contrary to human TG, microbial TG is calcium independent, has a lower molecular weight, has a single structural domain and exhibits a different reactivity to some food proteins. These characteristics make mTG a very useful tool for modifying the functionality of proteins in food products[48,90]. The following are some observations where mTG may increase intestinal permeability by cross-linking amino acids or protein: 1. ...
... This probably represents one of the fastestgrowing areas of microbial transglutaminase usage, as reflected by an increasing number of patent applications filed on the application of microbial transglutaminase in medicine. 13 As a result of the increasing use of microbial transglutaminase in the food industry, the common Western diet now contains large amounts of microbial transglutaminase, 10,11 with the maximum daily intake ranging up to 15 mg. Each kilogram of food treated with microbial transglutaminase contains about 50-100 mg of microbial transglutaminase. ...
The incidence of celiac disease is increasing worldwide, and human tissue transglutaminase has long been considered the autoantigen of celiac disease. Concomitantly, the food industry has introduced ingredients such as microbial transglutaminase, which acts as a food glue, thereby revolutionizing food qualities. Several observations have led to the hypothesis that microbial transglutaminase is a new environmental enhancer of celiac disease. First, microbial transglutaminase deamidates/transamidates glutens such as the endogenous human tissue transglutaminase. It is capable of crosslinking proteins and other macromolecules, thereby changing their antigenicity and resulting in an increased antigenic load presented to the immune system. Second, it increases the stability of protein against proteinases, thus diminishing foreign protein elimination. Infections and the crosslinked nutritional constituent gluten and microbial transglutaminase increase the permeability of the intestine, where microbial transglutaminases are necessary for bacterial survival. The resulting intestinal leakage allows more immunogenic foreign molecules to induce celiac disease. The increased use of microbial transglutaminase in food processing may promote celiac pathogenesis ex vivo, where deamidation/transamidation starts, possibly explaining the surge in incidence of celiac disease. If future research substantiates this hypothesis, the findings will affect food product labeling, food additive policies of the food industry, and consumer health education.
© The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute.
... Contrary to human TG, microbial TG is calcium independent, has a lower molecular weight, has a single structural domain and exhibits a different reactivity to some food proteins. These characteristics make mTG a very useful tool for modifying the functionality of proteins in food products [48,90]. ...
The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry , claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression.
Copyright © 2015. Published by Elsevier B.V.
... This probably represents one of the fastestgrowing areas of microbial transglutaminase usage, as reflected by an increasing number of patent applications filed on the application of microbial transglutaminase in medicine. 13 As a result of the increasing use of microbial transglutaminase in the food industry, the common Western diet now contains large amounts of microbial transglutaminase, 10,11 with the maximum daily intake ranging up to 15 mg. Each kilogram of food treated with microbial transglutaminase contains about 50-100 mg of microbial transglutaminase. ...
