49 results about "Pyruvic Kinase" patented technology

The invention provides a valine production strain and a construction method and application thereof, a designed acetohydroxy acid synthase mutant is that the 88th basic group of an ilvB gene is changed from a to c, the 382nd basic group is changed from a to g, the 413th basic group is changed from c to t, the gene sequence of a designed artificial operon comprises a promoter, an ilvB (A138V) gene or ilvB (Q30K, S128G, A138V) gene of coding mutated acetohydroxy acid synthase, and an ilvN (G20D, I21D, I21D, I21D, I21D, I21D, I21D, I21D) gene. I22F) gene, a pyk gene for coding pyruvate kinase, and a terminator; by designing a specific acetohydroxyacid synthase mutant and related biological materials and artificial operon, the strain constructed by directional modification of the strain by using a pK18mobsacB system gene editing technology based on allele exchange has the advantages of good genetic stability, high fermentation yield and the like, and valine can be stably produced.

Methods for preparing pyruvate kinase (PK) activators or salts or hydrates thereof are provided herein. Synthetic methods for preparing pyruvate kinase (PK) activators, or salts or hydrates thereof, are provided herein. Such activators may be prepared using compounds having formula (A-1) and / or formula (B-1). Specific PK activators and various intermediates prepared by and / or used by the synthetic methods described herein are also disclosed.

The invention discloses application of eupatolide in preparation of a medicine for preventing and treating inflammatory bowel disease, application of eupatolide in preparation of a medicine for preventing and treating inflammatory bowel disease and application of a medicine preparation containing eupatolide in preparation of a medicine for preventing and treating inflammatory bowel disease, and researches that eupatolide (EPT) can be used for preparing the medicine for preventing and treating inflammatory bowel disease through targeting pyruvate kinase isoenzyme 2 (PKM2, Gene ID: 5135). The inflammatory response, glycolysis metabolism and mitochondrial homeostasis are synergistically regulated and controlled, so that the inhibition effect on the inflammatory bowel disease is exerted. Meanwhile, EPT has the advantages of being low in dosage, feasible in oral administration, free of obvious toxic and side effects and the like, and a solid experimental basis is provided for further developing EPT into candidate drugs for preventing and treating inflammatory bowel diseases.

The invention relates to a pyruvate kinase-targeted compound shown as a formula I, a preparation method and application thereof, and application of the pyruvate kinase-targeted compound serving as a plant antibacterial agent, and part of the pyruvate kinase-targeted compound shows excellent bactericidal activity.

Described herein are compounds that activate pyruvate kinase, pharmaceutical compositions, and methods of using the same. The compounds are represented by Formula (I), wherein R 1 , R 2 , R a , R b , R j , R k , and Q are as defined herein.

The invention relates to Corynebacterium glutamicum with high indigo yield as well as a construction method and application thereof, and belongs to the technical field of gene recombination fermentation. The recombinant corynebacterium glutamicum can be used for overexpression of the following genes: a D-glucose-6-phosphate dehydrogenase gene zwf, a II type deoxyarabinose type heptulose phosphate synthase gene aroG and a flavin-containing monooxygenase gene CcFMO. The recombinant corynebacterium glutamicum can weaken the following genes: a pyruvate kinase gene pyk and a tryptophan synthase gene trpB. The corynebacterium glutamicum is used for overexpressing a zwf gene, an aroG gene and a CcFMO gene, weakening a pyk gene and a trpB gene and enhancing the expression quantity of an indole synthetic pathway related enzyme gene, so that the yield of the corynebacterium glutamicum at a shake flask stage reaches 619mg / L in a fermentation production process of indigo under the condition of not additionally adding tryptophan. The invention provides the recombinant corynebacterium glutamicum with high indigo yield, which is low in production cost, good in stability and high in synthesis efficiency, and is suitable for practical popularization and application.

Provided herein are amorphous and crystalline hemisulfate salt forms of the formula.Also provided are pharmaceutical compositions comprising the amorphous and crystalline hemisulfate salt forms, methods for their manufacture, and uses thereof for treating conditions associated with pyruvate kinase such as e.g., pyruvate kinase deficiency.

The invention relates to the technical field of biological medicines, in particular to application of tetramer-form pyruvate kinase type 2 (PKM2) in preparation of a medicine for treating obesity. Pyruvate kinase type 2 is a key enzyme in a glycolytic pathway and has two conformations of dimer and tetramer, and the tetramer-form enzyme has high activity. The invention discovers that the PKM2 tetramer stabilizer TEPP-46 can stabilize PKM2 in a high-activity tetramer state and improve obesity-related metabolic disorder induced by high fat diet. The invention discloses a new way for regulating and controlling energy metabolism by stabilizing the form of the PKM2 tetramer, and provides a new medicine application direction for treating obesity and related metabolic diseases.

Provided herein is the use of particular dose levels or amounts of certain pyruvate kinase activators or pharmaceutically acceptable salts or compositions thereof, for treating anemia associated with low risk MDS, lower risk MDS and / or intermediate risk MDS (collectively, LRMDS) and other conditions.

The invention relates to compounds of formula (Ia) and to their use in treating or preventing an inflammatory disease, a disease associated with an undesirable immune response, cancer, obesity, a diabetic disease or a blood disorder:wherein RA, RB, RC and RD, X, Y1, Y2, Y3, Z1, Z2 and m are as defined herein.

Provided herein are methods for preparing activators of Pyruvate Kinase (PK) or a salt or a hydrate thereof, as well as intermediates useful in the preparation of such compounds or salts or hydrates thereof. Also provided are a number of crystalline forms of select compounds or salts or hydrates disclosed herein.

The invention discloses a method for detecting the concentration of acetic acid in an anaerobic fermentation system by using a bioelectrochemical sensor, acetic acid is detected by using the bioelectrochemical sensor, the bioelectrochemical sensor comprises a screen-printed electrode, and the working surface of the screen-printed electrode is modified with reduced graphene oxide and polymethylene blue. The working surface of the screen printing electrode is connected with acetokinase, pyruvate kinase and lactic dehydrogenase through a cross-linking agent. According to the method, the adopted sensor has better conductivity, higher response speed and higher current intensity, when the sensor is used for detecting the concentration of acetic acid in a fermentation system, the sensor has the advantages of being easy to operate, low in sample consumption, low in price, high in accurate measurement precision, high in detection speed and the like, and rapid detection of the concentration of acetic acid can be achieved; the acetic acid concentration in the anaerobic fermentation process in different periods can be timely and accurately obtained, effective data can be provided for anaerobic fermentation analysis, and the method has important significance for monitoring the process stability of anaerobic fermentation.

The present application provides a Pichia pastoris engineering bacterium and a kit and application thereof, a method for obtaining the Pichia pastoris engineering bacterium, a method for improving glucose oxidase yield of the Pichia pastoris, and a method for producing glucose oxidase, wherein the Pichia pastoris engineering bacterium carries a glucose oxidase gene and a pyruvate kinase gene. The Pichia pastoris engineering bacterium of the present application can realize high glucose oxidase yield and high enzyme activity, and lays a good foundation for large-scale production of glucose oxidase.

Provided for are activators of pyruvate kinase isoform M2 (PKM2), pharmaceutical compositions thereof, and related methods of treating neurologic and neurodegenerative disease as well as well as other PKM2-associated disorders.

The application relates to the technical field of engineering bacteria, and particularly discloses recombinant Escherichia coli for synthesizing fucosyllactose as well as a construction method and application thereof. In the genome of the recombinant Escherichia coli, phosphofructokinase genes or phosphofructokinase genes and pyruvate kinase genes are knocked out, so that glucose carbon flow is reduced to flow to a tricarboxylic acid cycle required for cell growth, and the intake of glucose carbon flow is forced to flow more to the synthesis of products (GDP-L-fucose in the synthesis of FL), and the synthesis efficiency of the products is improved. Meanwhile, the glucose carbon flow flowing to the cell growth is greatly reduced, and the glucose effect can be removed, so that the tolerance of the fermentation process to excessive glucose residues is improved, and the difficulty of downstream production amplification is reduced. The recombinant Escherichia coli uses glycerol and glucose compound carbon sources as raw materials, uses lactose as a substrate, and has a 3-fucosyllactose yield of 73.88 g / L in a 5L tank fermentation, which is the highest level reported at present.

Provided herein are methods of treating sickle cell disease, methods of increasing hemoglobin levels in a subject diagnosed with sickle cell disease, and methods of reducing hemolysis-associated complications in a subject diagnosed with sickle cell disease, together with kits for such treatments, in a subject in need thereof, comprising administering a Gardos channel inhibitor such as 2,2-bis(4-fluorophenyl)-2-phenylacetamide and a pyruvate kinase activator such as N-(4-((4-(Cyclopropylmethyl)-1-piperazinyl)carbonyl)phenyl)-8- quinolinesulfonamide to the subject. Subjects eligible for treatment include subjects as having hemolysis dominant (HD) sickle cell disease on the basis of laboratory markers, clinical history, and / or sequelae.

The invention discloses recombinant escherichia coli, a construction method thereof and application of the recombinant escherichia coli in production of 3-dehydroshikimic acid, and belongs to the technical field of bioengineering. According to the recombinant escherichia coli, escherichia coli FMME-DHS03 is used as an original strain, pyruvate kinase gene pykA is knocked out, excessive 3-dehydroquinic acid synthase gene aroB, transketolase gene tktA and galactose permease gene galP are added, the finally obtained recombinant strain is fermented for 40 h, the yield of 3-dehydroshikimic acid reaches 130.9 g / L, and the yield of glucose reaches 0.55 g / g. The process for producing the 3-dehydroshikimic acid through fermentation is simple and easy to operate, free of additional antibiotics, short in period, high in yield, low in culture medium cost and suitable for industrial production.

Provided is a chiral cannabidiol (CBD) derivative drug, comprising four chiral derivatives, i.e., (7S)-(-)-CIAC001, (7R)-(-)-CIAC001, (7S)-(+)-CIAC001, and (7R)-(+)-CIAC001; and a use of the four chiral derivatives of CBD in the treatment of neuroinflammation and opioid addiction. Also disclosed are anti-neuroinflammation effects and the ability to regulate the activity of pyruvate kinase M2 (PKM2) of CBD analogs.

A method for treating brain injury in a subject comprises administering a therapeutically effective amount of a PKM2 (pyruvate kinase M2) protein variant. The protein variant is delivered systemically and can reduce tissue damage after ischemic brain tissue reperfusion. The methods specifically involve the use of G415R mutants of PKM2 protein variants. The treatment is suitable for brain injury caused by hemorrhagic stroke and ischemic stroke. The PKM2 protein variants are ideally administered intravenously within one hour of reperfusion to maximize their therapeutic efficacy.

This renal fibrosis inhibitor contains a substance that interferes with pyruvate kinase M2.

A joint detection kit for detecting intestinal polyp factors, and a preparation method therefor, a detection method therefor and the use thereof. The joint detection kit at least comprises a plurality of test strips for detecting the following indicators: M2-pyruvate kinase, matrix metalloproteinase 9, myeloperoxidase, glutathione S-transferase Pi, cytidine deaminase, retinol binding protein 4, serine protease inhibitor F2, calprotectin and fecal occult blood. Conjugate pads (2) of each reagent strip are coated with detection antibody-colloidal gold conjugates. Detection lines (3) of the reagent strip are coated with specific capture antibodies, and the specific capture antibodies on each test strip are different. The joint detection performed by the joint detection kit can effectively improve the sensitivity and specificity of the detection on intestinal polyps. The detection time is merely 15 min, with the detection rate of more than 91%. Therefore, the accuracy on the detection and diagnosis of colorectal cancer caused by intestinal polyps is improved.

The invention provides a tumor-targeting nanometer generator for optically-controlled chemical generation of peroxynitrite and a preparation method and application thereof.The tumor-targeting nanometer generator for optically-controlled chemical generation of peroxynitrite comprises an inner core and a coating layer coating the inner core, the inner core comprises BNN-6-loaded Prussian blue, and the coating layer comprises a BNN-6-loaded Prussian blue and a BNN-6-loaded Prussian blue. The coating layer comprises a tumor cell membrane. According to the present invention, the specific generation of ONOO <-> on tumor cells under the irradiation of the near-infrared I region light can be achieved, the activity of pyruvate kinase (PK) and glutaminase (GLS) can be inhibited, and the glycolysis and the glutamine metabolism of the tumor cells can be destroyed;

An in vitro method for assessing or predicting the response of a human patient to periodontal disease treatment is disclosed. The method is based on the insight that biomarker proteins are determined. Thus, in a saliva sample of a patient, the concentration of a specific combination of proteins is measured. One such combination is hemoglobin subunit delta (Hb-delta) and pyruvate kinase (PK). Another combination is at least two of alpha-1-acid glycoprotein (A1AGP), pyruvate kinase (PK), and matrix metallopeptidase-8 (MMP-8), and keratin-4 (K-4). A third combination is alpha-1-acid glycoprotein (A1AGP), pyruvate kinase (PK), and S100 calcium-binding protein A8 (S100A8). Based on the measured concentrations, at least one value is determined that reflects the joint concentration of this proteins. The at least one value can be indicative of the likelihood that the human patient has or will successfully treat periodontitis. The at least one value can be compared to at least one threshold value that reflects the joint concentration in the same way that is associated with successful treatment of periodontitis. This comparison allows to assess whether the test value is an indication of the periodontal treatment status of the patient.

Provided herein is the use of pyruvate kinase (PK) activators or pharmaceutically acceptable salts or compositions thereof, for treating renal fibrosis and other renal diseases.

The invention relates to application of pyruvate kinase (PKM), triosephosphate isomerase (TPI1), alpha-enolase (ENO1) and lactic dehydrogenase (LDHB) in urine in preparation of medicines for exercise function evaluation (exercise intensity, exercise density, exercise duration, exercise function, exercise posture and physiological state), exercise risk prediction, exerciser physique evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise function evaluation, exercise and scientific exercise guidance, exercise scheme screening and other reagents are applied. Research proves that the proteins PKM, TPI1, ENO1 and LDHB in urine are key proteins for exercise training monitoring for the first time. Compared with the prior art, the expression of the four proteins in a urine sample after movement is obviously increased. The sensitivity and the specificity of various purposes such as function evaluation, exercise risk prediction and scientific exercise guidance of exercise training can be improved through independent use of one of the components and combined use of multiple components.

The application specifically relates to a method for preparing glutathione by immobilized enzyme and application. The method for preparing glutathione provided by the application comprises synthesizing glutathione by using saccharomyces cerevisiae haploid ascospores as a fixed enzyme catalyst to catalyze substrate reaction, using an ATP in-situ regeneration reaction system of phosphoenolpyruvate as an energy supply system, the saccharomyces cerevisiae haploid ascospores are knocked out or inactivated in combination of one or more than two of cell wall beta-glucan synthesis genes, and GSH1 genes, GSH2 genes and PYK1 genes are co-expressed. The saccharomyces cerevisiae haploid ascospores for simultaneously producing GSH1, GSH2 and pyruvate kinase are used as a fixed enzyme catalyst to catalyze synthesis of glutathione, three enzymes no longer need to be added externally, raw material cost is greatly reduced, the obtained product is easy to purify, and the prepared glutathione is high in purity.

Disclosed is an in vitro method for assessing whether a human patient suffering from periodontitis has mild periodontitis or advanced periodontitis. The method is based on the insight to determine a selection of two biomarker proteins. Accordingly, in a sample of saliva a patient suffering from periodontitis, the concentrations are measured of the proteins Pyruvate Kinase (PK) and at least one of Matrix metalloproteinase-9 (MMP9), S100 calcium-binding protein A8 (S100A8), and Hemoglobin subunit beta (Hb-beta); or of the proteins Matrix metalloproteinase-9 (MMP9) and at least one of S 100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9). Based on the concentrations as measured, a value is determined reflecting the joint concentrations for said proteins. This value is compared with a threshold value reflecting in the same manner the joint concentrations associated with advanced periodontitis. The comparison allows assessing whether the testing value is indicative of the presence of advanced periodontitis or of mild periodontitis in said patient. Thereby, typically, a testing value reflecting a joint concentration below the joint concentration reflected by the threshold value is indicative for mild periodontitis in said patient, and a testing value reflecting a joint concentration at or above the joint concentration reflected by the threshold value, is indicative for advanced periodontitis in said patient.

The present application relates to the technical field of bioengineering, and particularly relates to a recombinant Saccharomyces cerevisiae and a construction method and application thereof, comprising the following steps: step one, using the whole genome of Enterococcus faecalis as a template, a recombinant strain SC1-1 is constructed; step two, using the recombinant strain SC1-1 as a primary strain, L-lactate dehydrogenase CYB2 gene of Saccharomyces cerevisiae is knocked out to obtain a recombinant strain SC2; step three, using the recombinant strain SC2 as a primary strain, branched-chain-2-oxo acid decarboxylase THI3 gene of Saccharomyces cerevisiae is knocked out to obtain a recombinant strain SC3; step four, using the whole genome of Saccharomyces cerevisiae as a template, a recombinant strain SC4 is constructed. The present application innovatively optimizes the source of L-lactate dehydrogenase L-LDH, knocks out L-lactate dehydrogenase CYB2 and branched-chain-2-oxo acid decarboxylase THI3, overexpresses pyruvate kinase CDC19 and H(+)-ATPase PMA2, and makes the L-lactic acid production of Saccharomyces cerevisiae increase to 33.45 g / L.

Described herein are methods for using compounds that activate pyruvate kinase.