Collagens are fundamental constituents of the extracellular matrix and are the most abundant proteins in mammals. Collagens belong to the family of fibrous or fiber-forming proteins that self-assemble into fibrils that define their mechanical properties and biological functions. Up to now, 28 members of the collagen superfamily have been recognized. Collagen biosynthesis occurs in the endoplasmic reticulum, where specific post-translational modification-glycosylation-is also carried out. The glycosylation of collagens is very specific and adds β-d-galactopyranose and β-d-Glcp-(1→2)-d-Galp disaccharide through β-O-linkage to hydroxylysine. Several glycosyltransferases, namely COLGALT1, COLGALT2, LH3, and PGGHG glucosidase, were associated the with glycosylation of collagens, and recently, the crystal structure of LH3 has been solved. Although not fully understood, it is clear that the glycosylation of collagens influences collagen secretion and the alignment of collagen fibrils. A growing body of evidence also associates the glycosylation of collagen with its functions and various human diseases. Recent progress in understanding collagen glycosylation allows for the exploitation of its therapeutic potential and the discovery of new agents. This review will discuss the relevant contributions to understanding the glycosylation of collagens. Then, glycosyltransferases involved in collagen glycosylation, their structure, and catalytic mechanism will be surveyed. Furthermore, the involvement of glycosylation in collagen functions and collagen glycosylation-related diseases will be discussed.

Glycosyltransferases (GTs) catalyze the transfer of active monosaccharide donors to carbohydrates to create a wide range of oligosaccharide structures. GTs display strong regioselectivity and stereoselectivity in producing glycosidic bonds, making them extremely valuable in the in vitro synthesis of oligosaccharides. The synthesis of oligosaccharides by GTs often gives high yields; however, the enzyme activity may experience product inhibition. Additionally, the higher cost of nucleotide sugars limits the usage of GTs for oligosaccharide synthesis. In this review, we comprehensively discussed the structure and mechanism of GTs based on recent literature and the CAZY website data. To provide innovative ideas for the functional studies of GTs, we summarized several remarkable characteristics of GTs, including folding, substrate specificity, regioselectivity, donor sugar nucleotides, catalytic reversibility, and differences between GTs and GHs. In particular, we highlighted the recent advancements in multi-enzyme cascade reactions and co-immobilization of GTs, focusing on overcoming problems with product inhibition and cost issues. Finally, we presented various types of GT that have been successfully used for oligosaccharide synthesis. We concluded that there is still an opportunity for improvement in enzymatically produced oligosaccharide yield, and future research should focus on improving the yield and reducing the production cost.

Simple noninvasive evidence-based interventions for caries are needed to overcome limitations in the restorative paradigm. The self-assembling peptide P11-4 is a noninvasive intervention that regenerates enamel in initial caries lesions.
The authors conducted a systematic review and meta-analysis on the effectiveness of the P11-4 products Curodont Repair (Credentis; now manufactured by vVARDIS) (CR) and Curodont Repair Fluoride Plus (Credentis; now manufactured by vVARDIS) on initial caries lesions. Primary outcomes were lesion progression after 24 months, caries arrest, and cavitation. Secondary outcomes were changes in merged International Caries Detection and Assessment System score categories, quantitative light-induced fluorescence (QLF; Inspektor Research System), esthetic appearance, and lesion size.
Six clinical trials met the inclusion criteria. Results of this review represent 2 primary and 2 secondary outcomes. When compared with parallel groups, use of CR likely results in a large increase in caries arrest (relative risk [RR], 1.82 [95% CI, 1.32 to 2.50]; 45% attributable risk [95% CI, 24% to 60%]; number needed to treat [NNT], 2.8) and likely decreases lesion size by a mean (SD) of 32% (28%). The evidence also suggests that use of CR results in a large reduction in cavitation (RR, 0.32 [95% CI, 0.10 to 1.06]; NNT, 6.9) and is uncertain about lowering merged International Caries Detection and Assessment System score (RR, 3.68 [95% CI, 0.42 to 32.3]; NNT, 19). No studies used Curodont Repair Fluoride Plus. No studies reported adverse esthetic changes.
CR likely has clinically important effects on caries arrest and decreased lesion size. Two trials had nonmasked assessors, and all trials had elevated risks of bias. The authors recommend conducting longer trials. CR is a promising treatment for initial caries lesions. The protocol for this systematic review was registered a priori with PROSPERO (304794).

Triterpenoid saponins are widely used in medicine, health cares, cosmetics, food additives and agriculture because of their unique chemical properties and rich pharmacological activities. UDP-dependent glycosyltransferases (UGTs) are the key enzymes involved in triterpenoid saponin biosynthesis, and play important roles in the diversity of triterpenoid saponin structures and pharmacological activities. This review summarized the UGTs involved in plant triterpenoid saponin biosynthesis based on the sources of UGTs and the types of receptors. Moreover, the application of UGTs in heterologous biosynthesis of triterpenoid saponins based on synthetic biology was also discussed.

UNASSIGNED: The present systematic review was conducted to investigate the effect of the self-assembling peptide (SAP) - P11-4 in the remineralization of enamel caries.
UNASSIGNED: The systematic search for studies was conducted through CINAHL, EMBASE, MEDLINE, Scopus, PsychINFO, and various key journals. This review was conducted in adherence to PRISMA standards and was registered in PROSPERO with registration number CRD42019110156. The methodological quality of the studies was graded through Cochrane\'s tool of risk of bias in non-randomized studies - of interventions (ROBINS-I).
UNASSIGNED: In total, 91 studies were identified for screening, and 12 studies were eligible. Ten studies showed effective enamel remineralization with P11-4 compared to controls. One study showed a combination of P11-4 with fluoride varnish or Casein Phosphopeptide-Amorphous Calcium Phosphate Fluoride (CPP-ACPF) leads to significantly higher remineralization compared to P11-4 alone. Quality assessment of study showed 6 (50%) studies as medium risk of bias and 6 (50%) studies as low risk of bias.
UNASSIGNED: To conclude, the present study results showed SAP- P11-4 is effective in the remineralization of enamel caries.

Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLex is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLex tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde\'s two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.

Quercetin and its derivatives are important metabolites that belong to the flavonol class of flavonoids. Quercetin and some of the conjugates have been approved by the FDA for human use. They are widely distributed among plants and have various biological activities, such as being anticancer, antiviral, and antioxidant. Hence, the biosynthesis of novel derivatives is an important field of research. Glycosylation and methylation are two important modification strategies that have long been used and have resulted in many novel metabolites that are not present in natural sources. A strategy for modifying quercetin in E. coli by means of glycosylation, for example, involves overexpressing respective glycosyltransferases (GTs) in the host and metabolic engineering for increasing nucleoside diphosphate sugar (NDP sugar). Still others have used microorganisms other than E. coli, such as Streptomyces sp., for the biotransformation process. The overall study of the structural activity relationship has revealed that modification of some residues in quercetin decreased one activity but increased others. This review summarizes all of the information mentioned above.

Progress in the functional biochemical analysis of plant glycosyltransferases (GTs) has been slow because plant GTs are generally membrane proteins, operate as part of larger, multimeric complexes, and utilize a vast complexity of substrate acceptors. Therefore, the field would benefit from development of adequate high throughput expression as well as product detection and characterization techniques. Here we review current approaches to tackle such obstacles and suggest a new path forward: nucleic acid programmable protein arrays (NAPPA) with liquid sample desorption ionization (LS-DESI-MS) mass spectrometry. NAPPA utilizes in vitro transcription and translation to produce epitope-tagged fusion proteins from cloned GT cDNAs. LS-DESI is a soft ionization technique that allows rapid and sensitive MS-based product characterization in situ. Coupling both approaches provides the opportunity to examine individual GT functions as well as protein-protein interactions. Furthermore, advances in automated oligosaccharide synthesis and lipid nanodisc technology should allow testing of plant GT activity in presence of numerous substrate acceptors and lipid environments in a high throughput fashion. Thus, NAPPA-DESI-MS has great potential to make headway in biochemical characterization of the large number of plant GTs.

Bacterial antibiotic resistance is a rapidly expanding problem in the world today. Functionalization of the outer membrane of Gram-negative bacteria provides protection from extracellular antimicrobials, and serves as an innate resistance mechanism. Lipopolysaccharides (LPS) are a major cell-surface component of Gram-negative bacteria that contribute to protecting the bacterium from extracellular threats. LPS is biosynthesized by the sequential addition of sugar moieties by a number of glycosyltransferases (GTs). Heptosyltransferases catalyze the addition of multiple heptose sugars to form the core region of LPS; there are at most four heptosyltransferases found in all Gram-negative bacteria. The most studied of the four is HepI. Cells deficient in HepI display a truncated LPS on their cell surface, causing them to be more susceptible to hydrophobic antibiotics. HepI-IV are all structurally similar members of the GT-B structural family, a class of enzymes that have been found to be highly dynamic. Understanding conformational changes of heptosyltransferases are important to efficiently inhibiting them, but also contributing to the understanding of all GT-B enzymes. Finding new and smarter methods to inhibit bacterial growth is crucial, and the Heptosyltransferases may provide an important model for how to inhibit many GT-B enzymes.

α-Dystroglycanopathy, an autosomal recessive disease, is associated with the development of a variety of diseases, including muscular dystrophy. In humans, α-dystroglycanopathy includes various types of congenital muscular dystrophy such as Fukuyama type congenital muscular dystrophy (FCMD), muscle eye brain disease (MEB), and the Walker Warburg syndrome (WWS), and types of limb girdle muscular dystrophy 2I (LGMD2I). α-Dystroglycanopathy share a common etiology, since it is invariably caused by gene mutations that are associated with the O-mannose glycosylation pathway of α-dystroglycan (α-DG). α-DG is a central member of the dystrophin glycoprotein complex (DGC) family in peripheral membranes, and the proper glycosylation of α-DG is essential for it to bind to extracellular matrix proteins, such as laminin, to cell components. The disruption of this ligand-binding is thought to result in damage to cell membrane integration, leading to the development of muscular dystrophy. Clinical manifestations of α-dystroglycanopathy frequently include mild to severe alterations in the central nervous system and optical manifestations in addition to muscular dystrophy. Eighteen causative genes for α-dystroglycanopathy have been identified to date, and it is likely that more will be reported in the near future. These findings have stimulated extensive and energetic investigations in this research field, and novel glycosylation pathways have been implicated in the process. At the same time, the use of gene therapy, antisense therapy, and enzymatic supplementation have been evaluated as therapeutic possibilities for some types of α-dystroglycanopathy. Here we review the molecular and clinical findings associated with α-dystroglycanopathy and the development of therapeutic approaches, by comparing the approaches with the development of Duchenne muscular dystrophy.