Glycosyltransferases: Unraveling Molecular Insights and Biotechnological Implications
Authors:   Department of Biochemistry, Government College Women University, Faisalabad, Pakistan, Majeed Humara Naz , Zahoor Muhammad Kashif ,   Department of Zoology, Government College University, Faisalabad, Pakistan, Shaheen Sumaira ,   Department of Biochemistry, Government College Women University, Faisalabad, Pakistan
Published: May 2024

Glycosyltransferases (GTs) are present in almost all living organisms; plants, animals and microorganisms. GTs transfer sugar molecule from nucleotide sugars to a wide range of molecules including hormones, secondary metabolites, biotic and abiotic chemicals. When glycosyltransferases add a sugar moiety in any molecule, the hydrophilicity of that molecule changes and thus alter the chemical properties of the molecule. This phenomenon is vital for appropriate working of living organisms. For the first time, X-ray structure of bacteriophage T4-glucosyltransferase was reported in 1994. In bacteria, GTs play essential roles in various biological processes such as cell wall biosynthesis, surface glycosylation and virulence factor production. The point mutation as well as the domain-swapping has been reported in Bacteria. The sequence change as well as the whole cells has been engineered in bacteria too. GTs play very important role in survival, growth, development, metabolism, detoxification, insecticide resistance, chitin formation, chemosensation, defense and immunity, involved in various signaling pathways, etc. In plants, glycosyltransferase enzymes play essential role in biosynthesis of cell wall components, secondary metabolites, and signaling molecules. GTs are involved in the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, leading to the formation of glycosidic bonds. GTs modify flavonoids, alkaloids and terpenoids, etc. with sugar residues and alter the solubility, stability, and bioactivity of these compounds and regulate the plant defense mechanism and interaction with insects, microorganisms and other organisms. GTs have direct impact on plant homeostasis. Site directed mutagenesis (SDM) in UGTs or GTs cause a change in substrate specificity and produce increased or total loss in the catalytic activity GTs. This kind of change demonstrated that a change in substrate specificity could cause better glycosylation and perked up anticancer activity of UGTs. GTs are also involved in glycosylaton of phytohormones and regulate their metabolism and signaling pathways. GTs are involved in the activity, stability, and transport of these hormones and influence the plant growth, development, and responses to various environmental stimuli. Four UGT families encoding 200 genes are reported in humans which regulate cell signaling, protein folding, immune response, growth and development, detoxification, metabolism and elimination of drugs, DNA methylation and histone modifications, transcriptional regulation, post-transcriptional regulation and post-translational regulation, synthesis of human blood group antigens A and B and recently GTs are also reported as linked with COVID-19-related loss of smell or taste. Various bioinformatics tools have been developed which would help analyse in silico, the structure of the GTs using any reference enzyme. The activity and the ordered structures along with various stability assays can be performed before to conduct in vitro analyses such as mutagenesis. Targeted mutagenesis have been reported through site directed mutagenesis (SDM) or domain-swapping. Standard protocols of molecular biology i.e. transformation, protein expression, extraction and purification followed by mass spectrometric analysis has been described. This molecular technique would direct future endeavours to engineer more glycosyltransferases to augment their activity with different substrates and provide a basis for more exploration of GTs as an active compound for potential anti-cancer therapeutics. Additionally, the role of GTs in medicine, food industry, pharmaceutical industry and agriculture is discussed. More research work is needed for the better understanding of the biological processes and the mechanisms of glycosyltransferases involved in cancer, tumor, drug metabolism etc. New era of engineering is awaited to engineer these GT enzymes in vitro to get them boost in industry as well as to help cure cancer and other diseases as well.