41 results about "Hexokinase" patented technology

The invention discloses a yarrowia lipolytica engineering strain with high yield of resveratrol as well as construction and application of the yarrowia lipolytica engineering strain, and belongs to the technical field of synthetic biology and metabolic engineering. The invention provides a yarrowia lipolytica engineering strain. A 4-coumaric acid-CoA ligase gene, a multi-copy resveratrol synthase gene, a transketolase 1 gene, a fusion gene of a histidine phosphate aminotransferase gene and a tyrosine ammonia lyase gene, a glycolytic pathway hexokinase gene, a 6-phosphofructokinase-1 gene and a phosphoglycerate kinase gene are integrated, so that the recombinant protein is obtained. According to the present invention, by using glucose as the substrate, the high yield of resveratrol can be achieved by using glucose as the substrate, the resveratrol yield during shake-flask culture fermentation can achieve 3.157 g / L, the resveratrol yield can be increased to 30.7 g / L during 5L-scale fed-batch fermentation, and the resveratrol yield can be increased to 30.7 g / L when the resveratrol yield is increased to 30.7 g / L when the resveratrol yield is increased to 30.7 g / L when the resveratrol yield is increased to 30.7 g / L; the maximum value is reported by the yarrowia lipolytica system at present.

The invention relates to the field of gene engineering and enzyme engineering, in particular to a thermostable hexokinase mutant and application thereof. The invention provides a hexokinase mutant, the amino acid sequence of the hexokinase mutant is mutated relative to the amino acid sequence of wild type hexokinase, one or more amino acids in the 204 site and the 344 site of the hexokinase mutant are mutated, and the mutated amino acids are selected from lysine, arginine, alanine or leucine; the amino acid sequence of the wild type hexokinase is as shown in SEQ ID NO. 1. The hexokinase mutant provided by the invention can effectively improve the stability of hexokinase from saccharomyces cerevisiae, is beneficial to solving the problem of instability of hexokinase in clinical detection of blood glucose and urine glucose, and has important application value.

The present invention relates to a non-invasive test for the detection of deep endometriosis. Particularly, although not exclusively, aspects of the present invention relate to one or more glycolysis-associated biomarkers (e.g., phosphoglycerate mutase 1 (PGAM1), Enolase-1 (ENO1), phosphofructokinase-1 (PFKP) and / or Hexokinase) and / or cytokines associated with aerobic glycolysis (e.g., IL-6 and / or TGF-β) which can be used to determine the likelihood of a subject having deep endometriosis based on a sample obtained from the subject.

The present invention discloses a recombinant saccharomyces cerevisiae for efficiently biosynthesizing inositol and its construction method and application, and belongs to the field of microbial genetic engineering. The recombinant saccharomyces cerevisiae of the present invention strengthens the expression of hexokinase gene hxk, inositol 3-phosphate synthase gene ino, inositol monophosphatase gene suhb, and realizes the rearrangement of glucose metabolism by knocking out the transcriptional repressor opi1 of inositol 3-phosphate synthase (Ino1) and glucose 6-phosphate dehydrogenase gene zwf1, and relieves feedback inhibition; In addition, the present invention further increases the yield of inositol by screening inositol external emission protein gene ompf, ompc and knocking out inositol internal transport protein gene itr1, itr2. The present invention realizes the efficient production of inositol (yield is as high as 195.7g / L), with good industrialization prospect.

Disclosed is an isoform of hexokinase 1 (HK1), namely hexokinase 1b (HK1b), for use as a prognosis marker and as a specific target for use in treatment of cancer.

The present invention provides a hexokinase, a preparation method thereof and an application. Among them, the hexokinase is obtained by mutating the hexokinase gene of wild-type Saccharomyces cerevisiae; the 52nd position of the amino acid sequence of the hexokinase is replaced and modified to E52V, and the 254th position is replaced and modified to S254P; the amino acid sequence is as shown in SEQ ID N0.1. The technical problem solved by the present invention is that the cost of the kit is high and the stability is poor during the detection of glucose by the hexokinase method.

The invention belongs to the technical field of polysaccharides, and particularly relates to a preparation method and application of mung bean sprout dietary fibers. The monosaccharide of the dietary fiber mainly comprises fucose, arabinose, galactose, glucose and mannose, and the molar ratio of the fucose to the arabinose to the galactose to the glucose to the mannose is 12.28: 2.60: 27.59: 7.06: 50.47. The structural unit is formed by mutually connecting-> 6)-alpha-D-Glcp-(1->,-> 5)-alpha-L-Araf-(1->,-> 3, 6)-alpha-D-Glcp-(1-> and the like to form a main chain, and a branch chain is mainly formed by connecting beta-D-Manp-(1-> to an O-3 position of a sugar residue-> 3, 6)-alpha-D-Glcp-(1-> and the like. In-vitro cell experiments prove that the dietary fiber can improve the insulin resistance state of HepG2 cells, the glucose consumption and the cell glycogen synthesis effect are improved, the activity of hexokinase and pyruvate kinase is improved, and the dietary fiber has no toxic effect influence on the cell growth activity in vitro. Therefore, the dietary fiber has a potential effect of improving insulin resistance, and is expected to become a functional food raw material for treating diabetes.

The invention discloses application of a hexokinase HK3 inhibitor in preparation of a medicine for preventing / treating chronic obstructive pulmonary disease. According to the research, clinical chronic obstructive pulmonary disease lung tissue in-situ neutrophile granulocyte sample transcriptome sequencing finds that differential genes are concentrated in a neutrophile granulocyte chemotactic pathway, enrichment expression of HK3 in neutrophile granulocytes is further analyzed, and expression enhancement in the chronic obstructive pulmonary disease neutrophile granulocytes is achieved; further research finds that the HK3 inhibitor can effectively protect weight loss, protect lung functions, relieve lung injury and reduce lung tissue collagen deposition, and in-vitro experimental analysis finds that the HK3 inhibitor can relieve chronic obstructive pulmonary lung oxidation-antioxidant imbalance caused by neutrophil ROS. The research proves that the HK3 inhibitor has a clinical application value in prevention and treatment of chronic obstructive pulmonary disease, and has a wide application prospect.

The application discloses application of a peach fruit hexokinase PpHXK3 gene in preparation of a plant cold-resistant product, and is characterized in that the nucleotide sequence is shown as SEQ ID NO. 1, and the amino acid sequence is shown as SEQ ID NO. 2; a cloning method of PpHXK3 comprises the following steps: extracting total RNA of peach fruit and reversely transcribing the total RNA into cDNA as a template, and designing upper and lower amplification primers according to a gene sequence of PpHXK3; finally, a PpHXK3 gene amplification product is obtained through PCR amplification; the application of PpHXK3 in preparation of polygalacturonase PpPG21 inhibitors and / or polygalacturonase PpPG23 inhibitors, and the application of PpHXK3 in preparation of peach fruit cold-resistant products and heterologous plant cold-resistant products are also provided; and the advantages are that the decomposition of pectin is reduced, the integrity of a cell wall structure and the hardness of a fruit are maintained, the fruit has higher cold resistance, and cold damage in a storage and transportation process is reduced.

Described herein are UV-resistant or UV-protective biological devices and extracts produced therefrom. The biological devices include microbial cells transformed with a DNA construct containing genes for producing UV-resistant proteins such as, for example, hexokinase, heat shock proteins, alcohol dehydrogenase, transferrin, flavonol synthase, zinc oxidase, and iron oxidase. Methods for producing and using the devices are also described herein. Finally, compositions and methods for using the devices and extracts to reduce or prevent UV-induced damage or exposure to materials, items, plants, and human and animal subjects are described herein.

The invention relates to methods of inhibiting hair growth in a subject, the method comprises administering an inhibitor of lactic acid fermentation to the subject, wherein the inhibitor is selected from the group consisting of pyruvate dehydrogenase kinase inhibitor, desoxyrhapontigenin, a phosphofructokinases inhibitor, a thioredoxin-1 inhibitor, L- Asparaginase, a GLUT1 inhibitor, a glutaminase C inhibitor, a hexokinase inhibitor and an mTORCI and mTORC2 inhibitor. Also provided herein are compositions for inhibiting hair growth and methods of screening for inhibitors of hair growth.

The invention discloses application of a peach fruit hexokinase PpHXK3 gene in preparation of a plant cold-resistant product. The peach fruit hexokinase PpHXK3 gene is characterized in that a nucleotide sequence is shown as SEQ ID NO.1, and an amino acid sequence is shown as SEQ ID NO.2; the cloning method of the PpHXK3 comprises the following steps: extracting total RNA (Ribonucleic Acid) of peach fruits, reversely transcribing the total RNA into cDNA (Complementary Deoxyribonucleic Acid) as a template, designing upstream and downstream amplification primers according to a PpHXK3 gene sequence, and finally, carrying out PCR (Polymerase Chain Reaction) amplification to obtain a PpHXK3 gene amplification product. The invention further provides application of the PpHXK3 in preparation of a polygalacturonase PpPG21 inhibitor and / or a polygalacturonase PpPG23 inhibitor and application of the PpHXK3 in preparation of peach fruit cold-resistant products and heterologous plant cold-resistant products, and the PpHXK3 has the advantages that decomposition of pectin is reduced, integrity of a cell wall structure and hardness of fruits are maintained, so that the fruits have high cold resistance, and the yield of the fruits is increased. And the cold damage in the storage and transportation process is reduced.

The invention belongs to the technical field of biochemical energy batteries, and discloses an implantable biochemical energy battery array, a chip and application. Comprising a plurality of biochemical energy power generation units which are mutually connected through a microfluidic channel to form a biochemical energy power generation array, the power generation array is connected in series and in parallel to form a battery array, and glucose fluid flows through the microfluidic channel. The power generation unit comprises a positive electrode, a biochemical decomposition chamber and a negative electrode, carrier materials of hexokinase HK, glucose 6-phosphate dehydrogenase G6PD, glucose 6-phosphate lactonase PGLS and glucose 6-phosphate dehydrogenase 6PGDH are fixed in the biochemical decomposition chamber, and the negative electrode is coated with an artificial film assembled with NADPH transhydrogenase and mitochondrial respiratory chain compound protein. According to the invention, glucose is used as fuel of the cell for continuous power generation, and the flexible array biochemical energy cell which is miniaturized, high in load, long in endurance, capable of being shaped and high in energy density can be provided.

A compound represented by the structure of Formula (II): wherein U is N or CH; when X is O, NH, or a bond, Z is N and when X is S, Z is CH; Y is CH2, C=O, or C=S; when X is a bond, Y is C=O; R1 is optionally substituted aryl, heteroaryl, or C(=O)-ORa; R2 and R3 are halogen, NO2, CN, C1-C4 alkyl, OR4, and NR5aR5b; R4, Ra, R5a, and R5b are hydrogen or C1-C4 alkyl; n is 0; m is 0, 1 or 2; and p and q are 0, 1, 2, 3 or 4; and the use of such compounds for treating, inhibiting, or suppressing a hexokinase-2 (HK2)-expressing cancer.

Disclosed herein are methods of inhibiting hexanketokinase (KHK) in a biological sample or subject, and methods of treating or preventing a disease or condition (e.g., a disease or condition associated with KHK dysregulation), the method comprises administering to the biological sample or the subject an effective amount of a compound represented by Formula I or a compound of Table A or a pharmaceutically acceptable salt thereof. (I)

The invention discloses a preparation method and application of a mannose hexaphosphate kinase mutant. The method comprises the following steps: constructing a protein prediction model by utilizing AAindex based on PyPEF software; a mutation site combination is predicted through a protein prediction model, a mutant gene is generated according to the predicted mutation site combination, and the mutation site combination comprises H92L, E119R and A138R; the mutant gene is cloned to a pET-28a (+) expression vector and then is introduced into escherichia coli for expression and purification to obtain the mannokinase hexaphosphate mutant. The mutant overcomes the problems of low enzymatic activity, poor stability and the like, and the enzymatic activity of the synthesized M6P is improved by more than 15 times compared with that of a wild type.

Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue fever. Studies have shown that DENV interacts with metabolic pathways, in particular the glycolysis is increased in DENV-infected cells. However, the dependence of DENV on this pathway has not been investigated in details. The inventors identified an interaction between the non-structural protein 3 (NS3) of DENV and GCKR, a host protein that regulates the liver-specific hexokinase GCK. NS3 expression alone was found to increase glucose consumption and lactate secretion in an hepatic cell line expressing GCK. The inventors observed that GCKR interaction with GCK decreases DENV replication, supporting the role of NS3 as an inhibitor of GCKR function. By targeting NAD(H) biosynthesis with the antimetabolite 6-Amino-Nicotinamide (6-AN), the inventors decreased cellular glycolytic activity and inhibited DENV replication in hepatic cell. The present invention thus relates to the use of inhibitors of NAD biosynthesis for the treatment of dengue virus infections.

The invention discloses a metabolic antagonist solution which is obtained by dissolving a metabolic antagonist in water, the metabolic antagonist is L-2-enol hexolactone and / or 2-deoxy-D-glucose, and the invention also discloses an application of the metabolic antagonist solution in storage of crude rosin. The metabolism antagonist solution provided by the invention aims at glycolysis and energy metabolism of impurities such as pine needles and barks, and discoloration and degradation of the crude rosin in the storage process are blocked from the source; the L-2-enol hexanoic acid lactone oxidation product enters cells through glucose transporters such as GLUT1 / 3 / 4, competes for binding sites with glucose, and interferes with glycolysis and energy metabolism of impurities such as pine needles and barks; the 2-deoxy-D-glucose has a pyranoid ring conformation highly similar to that of glucose, is acidified into 2-deoxyglucose-6-phosphoric acid by hexokinase, and hijacks a glycolytic pathway, resulting in metabolic blocking and energy depletion.

The invention discloses a pharmaceutical composition for inhibiting the activity of fusarium solani and application of the pharmaceutical composition. The active ingredients of the pharmaceutical composition are composed of plant essential oil cinnamyl aldehyde and hexokinase inhibitor lonidamine. Wherein the essential oil cinnamyl aldehyde is used as a main bacteriostatic agent, and the hexokinase inhibitor lonidamine is used as a synergistic bacteriostatic agent. Based on the characteristic that cinnamyl aldehyde exerts the bacteriostatic activity by interfering glycometabolism, the bacteriostatic activity of the natural product cinnamyl aldehyde is effectively improved by combining with hexokinase inhibitor drug combination, and potential drugs and medication strategies can be provided for treatment of fungal keratitis caused by fusarium solani.

The invention discloses an effect of an Erzhi pill extract in improvement of D-gal induced astrocyte energy metabolism disorder. The method specifically comprises the following steps: inducing C8-D1A mouse astrocytes by using D-gal to establish an energy metabolism disorder model, screening out an optimal modeling condition, screening out the optimal administration concentration of the Erzhi pill extract by using an MTT experiment and an ATP kit, detecting the expression levels of glycogen synthase protein and glycogen synthase gene by using Western blot and RT-qPCR, and determining the energy metabolism disorder of the Erzhi pill extract according to the expression level of the Erzhi pill extract and the expression level of the Erzhi pill extract. The kit is used for detecting the levels of glucose-6-phosphoric acid, lactic acid and ATP (adenosine triphosphate) and the activity of hexokinase and glycogen phosphorylase a in cells, and the Erzhi pill extract can improve the glycogen metabolism of astrocytes, improve the generation of glycogenic lactic acid, further provide energy for the activity of neuronal cells and improve the energy metabolism disorder of D-gal induced astrocytes.

The application belongs to the field of biomedical technology, and aims to solve the problems of lack of metabolic typing characteristics in the current ESCC molecular typing method, lack of esophageal squamous cell carcinoma molecular typing method based on proteomics and metabolomics, and provides an esophageal squamous carcinoma ESCC molecular typing marker based on DIA proteomics and non-targeted metabolomics and its application. The marker is a combination of 4 proteins and 2 metabolites, the 4 proteins are: hexokinase 3 (HK3), Sec1 family domain protein 1 (SCFD1), septin 5 (SEPTIN5), and signal sequence receptor alpha subunit (SSR1); the 2 metabolites are creatine and 2-deoxy-D-glucose (2'DG). The application fills the gap of the molecular typing method based on proteomics and metabolomics in the field of esophageal squamous carcinoma research, and the proposed molecular typing model can be used as a method for diagnosis, treatment and prognosis evaluation of esophageal squamous carcinoma patients.

Described herein are UV-resistant or UV-protective biological devices and extracts produced therefrom. The biological devices include microbial cells transformed with a DNA construct containing genes for producing UV-resistant proteins such as, for example, hexokinase, heat shock proteins, alcohol dehydrogenase, transferrin, flavonol synthase, zinc oxidase, and iron oxidase. Methods for producing and using the devices are also described herein. Finally, compositions and methods for using the devices and extracts to reduce or prevent UV-induced damage or exposure to materials, items, plants, and human and animal subjects are described herein.

The application relates to the fields of genetic engineering and enzyme engineering, and particularly relates to a heat-stable hexokinase mutant and application thereof. The application provides a hexokinase mutant, wherein the amino acid sequence of the hexokinase mutant is mutated at one or more of positions 204 and 344 of the amino acid sequence of wild-type hexokinase, and the mutated amino acid is selected from lysine, arginine, alanine or leucine; and the amino acid sequence of the wild-type hexokinase is shown in SEQ ID NO. 1. The hexokinase mutant provided by the application can effectively improve the stability of hexokinase from Saccharomyces cerevisiae, and is beneficial to solving the instability problem of hexokinase in clinical detection of blood glucose and urine glucose, and has important application value.

The present invention relates to the field of pharmaceutical technology, and specifically relates to pyrimidine derivative hexokinase inhibitors, pharmaceutically acceptable salts thereof, esters thereof or stereoisomers thereof, pharmaceutical compositions and preparations containing the compounds, pharmaceutically acceptable salts thereof, esters thereof or stereoisomers thereof, methods for preparing the compounds, pharmaceutically acceptable salts thereof, esters thereof or stereoisomers thereof, and uses of the compounds, pharmaceutically acceptable salts thereof, esters thereof or stereoisomers thereof in the preparation of drugs for treating and / or preventing diseases mediated by KHK and related diseases.

Disclosed is use of inhibiting hexokinase isozyme 2 in the treatment of herpes simplex viral keratitis. The present application provides use of an inhibitor of hexokinase isozyme 2 in the preparation of a pharmaceutical composition for treating or preventing herpes simplex viral keratitis in an individual. The present application further provides a pharmaceutical composition for treating or preventing herpes simplex viral keratitis. The present application further provides a method for screening for a drug for treating or preventing herpes simplex viral keratitis. The present application further provides a screening system and a screening device for a drug for treating or preventing herpes simplex viral keratitis. The present application further provides a related computer-readable storage medium.

The present invention provides a hexokinase inhibitor, a hexokinase inhibitor ruthenium complex and its application in the preparation of anti-tumor drugs, belonging to the technical field of anti-tumor drugs. The present invention uses 2-deoxy-d-ribose as a parent nucleus to replace the 2-deoxy-D-glucose structure for modification. The present invention adopts deoxyribose and amino acids, which are endogenous substances in the human body, to construct a hexokinase inhibitor with a structure shown in Formula I with low drug toxicity and high anti-tumor biological activity. At the same time, the present invention introduces the concept of ruthenium complex on the basis of the hexokinase inhibitor with a structure shown in Formula I, and the obtained hexokinase inhibitor ruthenium complex can undergo molecular self-assembly in an aqueous solution to form self-assembled nanoparticles, thereby improving the targeting of tumors. At the same time, the hexokinase inhibitor ruthenium complex can act on the aerobic respiration and glycolysis pathways of tumor cells, effectively inhibit the energy metabolism pathways of tumor cells, and further enhance the anti-tumor activity.

Compositions and methods are provided for treating tumor cells in which tumor cells that overexpress monocarboxylic acid transporter 4 (Mct-4), HIF-1 [alpha], hexokinase-2, and / or CD147 are targeted by one or more metabolic inhibitors.

Disclosed herein are methods for inhibiting ketohexokinase (KHK) in a biological sample or subject, and methods for treating or preventing a disease or disorder (e.g., a disease or disorder related to KHK dysregulation), comprising administering to the biological sample or subject an effective amount of a compound represented by formula I or a compound in Table A, or a pharmaceutically acceptable salt thereof. JPEG2026514128000048.jpg5955

Inhibitors directed at enzymes of the pentose phosphate pathway of protozoan parasites, e.g., Trypanosoma cruzi glucokinase, are described. Inhibitors are derivatives of gossypol (2,2′-Bis(formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene). The inhibitors can specifically target glucokinase and hexokinase of Trypanosoma cruzi (T. cruzi), Trypanosoma brucei (T. brucei), and Leishmania spp. and are useful in treatment of parasitic diseases including Chagas' disease and African sleeping sickness, among others.

The application provides a glycyrrhizin metal complex, a preparation method thereof and application thereof in preparation of anti-tumor and anti-inflammatory drugs, and belongs to the technical field of anti-tumor drugs. The glycyrrhizin is metal-complexed with cobalt, nickel and rubidium to construct a hexokinase inhibitor. The results of examples show that, compared with the NS group, the glycyrrhizin metal complex provided by the application exhibits a significant inhibitory effect on hexokinase, and has a good anti-proliferation effect on A549 (human non-small cell lung cancer cells), MCF-7 (human breast cancer cells), SK-Mel-28 (human malignant melanoma cells) and SW480 (human pancreatic cancer cells). In addition, the glycyrrhizin metal complex provided by the application improves the inhibitory activity of glycyrrhizin on OH free radicals, and has stronger anti-inflammatory activity than glycyrrhizin.