20 results about "Nucleotidase" patented technology

The invention provides a uracil production strain and a construction method and application thereof.According to the strain, on an E.coli UR14 genome by means of a CRIPSR / Cas9 gene editing technology, firstly, psuG genes, preTA genes, rutA genes and upp genes are knocked out, so that decomposition of uracil is blocked; then, a uridine phosphorylase gene udp and a pyrimidine-5 '-nucleotide nucleotidase gene ppnN are subjected to overexpression, and synthesis and accumulation of uracil are synergistically enhanced; and finally, overexpression of the ribose phosphate mutase gene pgm further enhances the conversion of a by-product ribose phosphate 1-precursor 5-ribose phosphate 1-pyrophosphate and improves the carbon utilization rate, and the obtained strain has good genetic stability and high fermentation yield, can stably produce uracil, and has wide application prospects.

The present invention discloses the use of a nonspecific 5'-nucleotidase in the preparation of nicotinamide riboside. The nonspecific 5'-nucleotidase is selected from a nonspecific 5'-nucleotidase derived from Shewanella sp. HN-41. The nonspecific 5'-nucleotidase of the present invention can efficiently catalyze the hydrolysis of high-concentration nicotinamide mononucleotide (NMN) to produce nicotinamide riboside (NR), exhibits high enzymatic activity, and has value for industrial application.

The present invention relates to radio- and fluorescence-labeled compounds, as well as their use as Diagnostics for Detecting Ecto-5′-Nucleotidase (CD73). The invention is further directed to a pharmaceutical composition comprising said compounds as well as to the compounds and the pharmaceutical composition for use in a method of diagnosis of a disease associated with increased or decreased CD73-expression as well as in the treatment of a disease associated with increased CD73-expression.

Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and / or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

The present invention relates to an Escherichia coli that efficiently produces 5'-inosinic acid and its application, belonging to the field of bioengineering technology. In order to reduce the degradation of 5'-inosinic acid in Escherichia coli, four phosphatase encoding genes were knocked out using the CRISPR / Cas9 system, and it was found that knocking out the UMP phosphatase encoding gene nagD and the 5'-nucleotidase encoding gene ushA respectively can increase the production of 5'-inosinic acid. Subsequently, in order to inhibit the further conversion of 5'-inosinic acid into guanylate and adenylate, the 5'-inosinic acid dehydrogenase encoding gene guaB was knocked out alone. Finally, in order to enhance the supply and utilization of formyltetrahydrofolate required in the purine synthesis process, the promoter of the serine hydroxymethyltransferase encoding gene glyA was replaced with P tac The recombinant Escherichia coli produced 2113.12 mg / L of 5'-inosinic acid in 48 hours of fermentation, and no antibiotics were required during the fermentation process, indicating that the product has broad application prospects.

Provided are CD73 (also known as ecto-5'-nucleotidase) inhibitor compounds, and compositions and uses thereof for treating and / or preventing CD73-associated diseases, disorders, and conditions, including cancer-associated and immune-associated disorders. CD73 inhibitor compounds include compounds having a structure according to Formula I': (I') and pharmaceutically acceptable esters or salts thereof.

The invention belongs to the technical field of biological catalytic synthesis, and particularly relates to a method for synthesizing beta-nicotinamide mononucleotide (NMN) by enzyme catalysis, which comprises the following steps: by taking D-ribose as a starting substrate, and utilizing a three-step enzyme catalysis reaction system which is synergistically completed by an S-methyl-5-thioribose kinase mutant (SMTK), purine nucleotidase (PNP) and nicotinamide ribose kinase (NRK), synthesizing beta-nicotinamide mononucleotide (NMN) by enzyme catalysis. And efficient synthesis of the NMN is realized. In order to further optimize the cost, an ATP (adenosine triphosphate) regeneration system is innovatively introduced in the process, so that the consumption of ATP in the reaction process is effectively reduced. On the basis, by combining an enzyme directed evolution technology, an immobilized enzyme technology and a continuous reactor design, the catalytic reaction efficiency and the product purity level are remarkably improved. The whole process has the characteristics of greenness and environmental protection, the reaction conditions are mild and controllable, the product yield stably reaches more than or equal to 85%, and the requirements of industrial large-scale production are completely met.

The invention provides application of non-specific 5 '-nucleotidase in production of beta-nicotinamide ribose (NR), and belongs to the technical field of biology. The invention discovers that the non-specific 5 '-nucleotidase derived from specific bacteria has obviously better catalytic activity for catalyzing the hydrolysis of nicotinamide nucleotide (NMN) to generate beta-nicotinamide ribose (NR) compared with UshA derived from escherichia coli, and the 5'-nucleotidase can be used for large-scale industrial production of beta-nicotinamide ribose.

Methods of identifying compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and that possess particular pharmacokinetic characteristics are described herein. Methods of such compounds, and compositions comprising same, for the treatment and / or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, are also provided.

CD73 (also known as ecto-5′-nucleotidase) inhibitor compounds are provided, as well as compositions and uses thereof for treating or preventing CD73-associated or related diseases, disorders and conditions, including cancer- and immune-related disorders. CD73 inhibitor compounds include compounds having the structure set forth in Formula I′ and pharmaceutically acceptable esters or salts thereof.

The invention relates to the technical field of in-vitro detection reagents, in particular to a 5 '-nucleotidase calibrator and a preparation method thereof.The calibrator comprises 5'-nucleotidase, a borate buffering agent and animal serum, and the animal serum is selected from at least one of newborn calf serum, fetal calf serum, calf serum or sheep serum. The calibrator disclosed by the invention shows good stability and interchangeability, and ensures the detection accuracy of 5 '-nucleotidase.

The application provides a cytosine nucleoside producing strain and a construction method and application thereof, and the strain is constructed by using CRIPSR / Cas9 gene editing technology E. coli The cdd gene and cmk gene are knocked out on the UR12 genome, the nucleoside triphosphate reductase gene nrdD is weakened, and the nucleoside triphosphate pyrophosphatase gene nudG, the nucleoside diphosphate kinase gene ndk and the uridine acid kinase gene pyrH carrying a mutation point are overexpressed (D93A) The cytosine triphosphate synthase gene pyrG carrying a mutation point is introduced into the Corynebacterium glutamicum heterologously and in multiple copies (D160E、E162A、E168K，cgl) The bifunctional nucleotidase gene of Saccharomyces cerevisiae PHM8 (sce) The obtained strain has good genetic stability, high fermentation yield and can stably produce cytosine nucleoside.

Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and / or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

The present invention provides a cell including a recombinant DNA molecule including a first nucleic acid sequence encoding at least one first polypeptide being an enzyme selected from: inosine monophosphate dehydrogenase (Impdh), guanosine monophosphate synthetase (gmps), nucleotidase 5C (nt5c), polynucleotide phosphorylase (Pnp), or any combination thereof. Further provided is a method of using the cell of the invention, such as for synthesizing guanine.

Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and / or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

Various embodiments relate to compounds, having structures according to Structure A or Structure B, as specified herein. The compounds according to various embodiments may inhibit NT5C2 nucleotidase. The compounds according to various embodiments may synergistically decrease cell viability of NT5C2 R367Q mutant lymphoblasts when used in combination with 6-mercaptopurine (6-MP) to treat a cancer. The cancer may be, but is not limited to, acute lymphoblastic leukemia. Various embodiments relate to a compositions that may include one or more compounds according to any embodiment described herein or a pharmaceutically acceptable salt or derivative thereof and a pharmaceutically acceptable carrier. Various embodiments relate to methods of treating cancer. The method may comprise administering a therapeutically effective amount of one or more compounds according to any embodiment described herein or a pharmaceutically acceptable salt or derivative thereof.

This invention involves immunizing mice with human ecto-5′-nucleotidase (CD73) to obtain multiple monoclonal antibodies whose heavy-chain and light-chain sequences are both novel amino acid sequences and which can be used to prepare CD73 enzyme activity inhibitors and anti-tumor drugs.

The purpose of the present invention is to provide a novel method which makes it possible to produce a methyl compound by using a general organic raw material such as glycine, serine, formic acid, methanol, or glucose to efficiently regenerate SAM and promote a methylation reaction.　The present invention provides a method for producing a methyl compound using a cell in which the activity or expression of S-adenosylmethionine (SAM)-dependent methyltransferase and S-ribosylhomocysteine lyase (LuxS) is increased and which has been modified so as to reduce enzymatic activity of at least one selected from the group consisting of 5'-nucleotidase (UshA, UmpG, and / or UmpH), AMP nucleosidase (Amn and / or PpnN), adenine deaminase (AdeD), adenylate cyclase (CyaA), and S-adenosylmethionine decarboxylase (SpeD).

The present invention provides for compositions and methods for deploying ddhNTPs as immunomodulatory therapeutics to modulate P2 receptors, as nucleotidase inhibitors, for applications like host-acting anti-infectives, oncolytics, anti-aging agents, or tissue regeneration agents.