Functions of UDP-Glucuronosyltransferase (UGT)

UGT is a microsomal glycosyltransferase. The enzyme catalyzes the glucuronosylation reaction of glucuronic acid with a large number of chemicals. With the cloning of the UGT gene and the successful expression of the gene product, the function and gene structure of UGT have become better understood. UGT is mainly found in the endoplasmic reticulum membrane and nuclear membrane of hepatocytes. It is also present to varying degrees in other organs and tissues such as the kidney, gastrointestinal tract, skin, brain, etc. UGT metabolizes not only foreign chemicals but also endogenous chemicals such as bilirubin, short-chain fatty acids, bile acids, and fat-soluble vitamins. In addition, UGT has an important physiological role in the metabolism of steroids and thyroid hormones. It is also involved in the biosynthesis of sugar esters in the brain and the clearance of aromatic substances.

UGT Engineering Service at CD BioGlyco

CD BioGlyco has realized knockdown, insertion, suppression, overexpression, and many other purposes of genes. Our team will provide the best quality UGT gene editing services. The services include but are not limited to the following.

Fig.1 Types of UGT gene editing. (CD BioGlyco)

• UGT gene editing service
  UGT is common and widely studied in phase II drug metabolism. It is mainly involved in phenol, bilirubin, and steroid metabolism. It plays a central role in the metabolism and detoxification of a wide range of compounds. Members of this enzyme family catalyze the generation of glucuronic acid which is more polar and easier to excrete than the substrate molecule. We use various Techniques for Gene Editing to study the function of UGT genes in detoxification and their correlation with disease. We also exogenously express UGT genes by constructing microbial expression systems and insect cell expression systems. Various substrates are used to characterize their activities, and their applications in drug metabolism studies are explored. The UGT genes are involved in UDP-glucuronyltransferase 1A1 (UGT1A1), UDP-glucuronylglycosyltransferase 1A3 (UGT1A3), UDP-glucuronylglycosyltransferase 1A8 (UGT1A8), etc.

• UGT gene family analysis service
  There are still some species in which UGT has not been reported. We provide the UGT gene family analysis service. We analyze the UGT gene family by bioinformatics method and identify members of the UGT gene family. We also study the specific functions of the gene family through physical and chemical characterization, phylogenetic analysis, chromosomal localization, gene structure, conserved motif analysis, etc. Upon request, we also construct UGT gene mutants to validate the function of UGT and to clarify the detoxification function of UGT.

Published Data

Paper Title: Identification of a novel glucuronyltransferase from Streptomyces chromofuscus ATCC 49982 for natural product glucuronidation

Technology: Gene Knock-in

Journal: Applied Microbiology and Biotechnology

IF: 5.8

Published: 2022

Results: A putative UGT gene cluster was analyzed from the Streptomyces chromofuscus ATCC 49982 genome, which included a UGT gene (gcaC). The gcaC was cloned into Escherichia coli for heterologous expression. The results showed that the generated novel GcaC has broad substrate specificity. It catalyzes the generation of two products UDP-glucuronic acid and resveratrol. The present study provides a new method for the production of various natural products.

Fig.2 GcaC catalyzes the reaction between UDP-glucuronic acid and resveratrol. (Ren, et al., 2022)

Applications

• The relationship between plants and insects is constantly evolving. The use of UGT gene editing makes it possible to reverse insect resistance.
• UGTs in microorganisms are not well studied. The technologies for UGT gene editing are used to study the function of this type of enzyme in organisms.
• UGT abnormalities are correlated with the development of certain diseases. The technologies for UGT gene editing are used to study the mechanisms of disease development.

Highlights

• Compared to traditional gene modification techniques, our editing is highly efficient and minimizes the experimental period.
• We have a wide range of high-quality insect, yeast, mammalian, and bacterial expression systems to choose from.
• The use of UGT gene editing helps to study the detoxification function and thus provides a new direction for the development of new insecticides and drugs.

CD BioGlyco applies proven technologies for gene editing to realize the construction of multi-domain in vitro models. Our experienced researchers provide customized Gene Editing services and advice upon request. In addition to UGT, we also offer GAG Polymerase Engineering Service and Sulfotransferase Engineering Service. For detailed UGT gene editing services, please feel free to contact us.

Reference:

1. Ren, J.; et al. Identification of a novel glucuronyltransferase from Streptomyces chromofuscus ATCC 49982 for natural product glucuronidation. Applied Microbiology and Biotechnology. 2022, 106(3): 1165-1183.