185 results about "Mevalonic acid" patented technology

A microorganism having the ability to biosynthesize mevalonic acid from acetyl-CoA is obtained by transfecting a DNA participating in biosynthesis of mevalonic acid from acetyl-CoA into a host microorganism, preferably into a microorganism having only a non-mevalonic acid pathway, to express the DNA therein. Mevalonic acid can be efficiently produced by culturing the microorganism, and recovering mevalonic acid that is produced and accumulated in a large amount in the culture.

Methods for synthesizing isopentenyl pyrophosphate are provided. A first method comprises introducing into a host microorganism a plurality of heterologous nucleic acid sequences, each coding for a different enzyme in the mevalonate pathway for producing isopentenyl pyrophosphate. A related method comprises introducing into a host microorganism an intermediate in the mevalonate pathway and at least one heterologous nucleic acid sequence, each sequence coding for an enzyme in the mevalonate pathway necessary for converting the intermediate into isopentenyl pyrophosphate. The invention also provides nucleic acid sequences, enzymes, expression vectors, and transformed host cells for carrying out the methods.

The invention features methods for producing isoprene from cultured cells having increased expression levels and/or activity levels of a mevalonate kinase polypeptide and an isoprene synthase polypeptide. The invention also provides methods for producing isoprene from cultured cells having reduced accumulation of intermediates (such as mevalonate, isopentenyl diphosphate, 3,3-dimethylallyl diphosphate, geranyl diphosphate, or farnesyl diphosphate) in the biosynthesis of isoprene or isoprenoids that may otherwise cause undesirable amounts of growth inhibition, toxicity, or cell death. The resulting isoprene compositions may have increased yields and/or purity of isoprene.

The invention discloses a bacterial strain for producing farnesene and an application of the bacterial strain, belonging to the field of synthetic biology. The bacterial strain for producing the farnesene contains related genes for synthesizing the farnesene through a mevalonic acid pathway and codon optimization; and the sequence of a farnesene synthetic gene afs optimized by codons is as shown by SEQ ID NO.1. The bacterial strain can be used for producing the farnesene, and a seed solution of the bacterial strain is inoculated into a culture medium containing a carbon source to carry out prokaryotic expression to obtain the farnesene. The gene for synthesizing the farnesene is subjected to codon optimization or the farnesene is synthesized by using the mevalonic acid pathway to ensure that each protein is closer to a ratio of AtoB:ERG13:tHMG1:ERG12:ERG8:MVD1:Idi:IspA:AFS=1:10:2:5:5:2:5:2:2, so that the production of the farnesene can be further promoted. By adopting the bacterial strain, the output of the farnesene is greatly improved to be more than 1g/L.

The invention provides for methods for the production of mevalonate, isoprene, isoprenoid precursor molecules, and/or isoprenoids in cells via the heterologous expression of phosphoketolase enzymes.

The present invention provides a pharmaceutical kit useful for treating cancer cells in a mammal. Using this kit, the cancer cells are first sensitized by administering to the mammal an agent which comprises an effective amount of a HMG-CoA reductase inhibitor. The sensitized cancer cells are then treated with an anti-cancer agent which reduces the survival or growth of the cancer cells.

The present invention provides methods for treating a variety of hyperproliferative and inflammatory mucocutaneous disorders, including, basal cell carcinoma, squamous cell carcinoma, psoriasis and atopic dermatitis, as well as skin irritation and disorders associated with skin aging and skin photodamage using inhibitors of cholesterol metabolism. The present invention further relates to the discovery that the combined use of several inhibitors of cholesterol metabolism produces synergistic effects. Furthermore, the present invention is directed to the use of inhibitors of cholesterol metabolism as excipients to enhance the effects of antiinflammatory drugs.

Provided herein are metabolically modified microorganisms characterized by having an increased keto-acid flux when compared with the wild-type organism and comprising at least one polynucleotide encoding an enzyme, and causing the production of a greater quantity of a chemical product when compared with the wild-type organism. The recombinant microorganisms are useful for producing a large number of chemical compositions from various nitrogen containing biomass compositions and other carbon sources. More specifically, provided herein are methods of producing alcohols, acetaldehyde, acetate, isobutyraldehyde, isobutyric acid, n- butyraldehyde, n-butyric acid, 2-methyl-l-butyraldehyde, 2-methyl-l -butyric acid, 3- methyl-l-butyraldehyde, 3 -methyl- 1 -butyric acid, ammonia, ammonium, amino acids, 2,3-butanediol, 1,4-butanediol, 2-methyl-l, 4-butanediol, 2-methyl- 1,4-butanediamine, isobutene, itaconate, acetoin, acetone, isobutene, 1,5-diaminopentane, L-lactic acid, D- lactic acid, shikimic acid, mevalonate, polyhydroxybutyrate (PHB), isoprenoids, fatty acids, homoalanine, 4-aminobutyric acid (GABA), succinic acid, malic acid, citric acid, adipic acid, p-hydroxy-cinnamic acid, tetrahydrofuran, 3-methyl-tetrahydrofuran, gamma-butyrolactone, pyrrolidinone, n-methylpyrrolidone, aspartic acid, lysine, cadeverine, 2-ketoadipic acid, and/or S-adenosyl-methionine (SAM), from a suitable nitrogen rich biomass.

The present invention provides pharmaceutical compositions, methods, combinations, and kits for treating a disorder related to elevated serum cholesterol concentration, for example, hypercholesterolemia, atherosclerosis, elevated LDL plasma levels, low HDL plasma levels, hypertriglyceridemia, hyperlipidemia, hypertension, cholesterol gallstones, and lipid storage diseases. The compositions, methods, combinations, and kits of the present invention are pharmaceutical compositions comprising atherapeutically effective amount of a lipid regulating agent, such as a HMG-CoA reductase inhibitor, and compound that inhibits cholesterol synthesis at a point between the formation of acetate and mevalonate. A typical pharmaceutical composition of the invention contains and effective amount of atorvastatin and an effective amount of policosanol.

Disclosed are the uses of specific genes of the mevalonate and isoprenoid biosynthetic pathways, and of inactive gene sites (the pseudogene) to (1) enhance biosynthesis of isopentenyl diphosphate, dimethylallyl diphosphate and isoprenoid pathway derived products in the plastids of transgenic plants and microalgae, (2) create novel antibiotic resistant transgenic plants and microalgae, and (3) create a novel selection system and/or targeting sites for mediating the insertion of genetic material into plant and microalgae plastids. The specific polynucleotides to be used, solely or in any combination thereof, are publicly available from GeneBank and contain open reading frames having sequences that upon expression will produce active proteins with the following enzyme activities: (a) acetoacetyl CoA thiolase (EC 2.3.1.9), (b) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase (EC 4.1.3.5), (c) HMG-CoA reductase (EC 1.1.1.34), (d) mevalonate kinase (EC 2.7.1.36), (e) phosphomevalonate kinase (EC 2.7.4.2), (f) mevalonate diphosphate decarboxylase (EC 4.1.1.33), (g) isopentenyl diphosphate (IPP) isomerase (EC 5.3.3.2), and (h) phytoene synthase (EC 2.5.1.32).

The invention provides a biological method for synthesizing alpha-pinene or beta-pinene from acetyl coenzyme A and a reconstitution cell capable of synthesizing the alpha-pinene or beta-pinene, wherein the acetyl coenzyme A is obtained from a simple starting material like glucose. The method for synthesizing the alpha-pinene or beta-pinene by adopting a biological process comprises the following steps: transferring acetyl coenzyme A acyltransferase, 3-hydroxy-3-methyl glutaryl coenzyme A synthase, hydroxymethyl glutaryl coenzyme A reductase, mevalonic acid kinase, mevalonic acid-5-phosphokinase, mevalonic acid-5-diphosphonic acid decarboxylase, isopentenylpyrophosphate isomerase, geranyldiphosphate synthetase and pinene synthase into an appropriate host cell by adopting metabolic engineering technology, and culturing the obtained reconstitution cell, so that the target product, namely alpha-pinene or beta-pinene can be obtained.

The invention belongs to the technical field of mineral engineering, and aims to provide a mineral separation process for recycling iron and rare earth in baotite magnetite flotation tailings. Three sections of ore grinding and three sections of magnetic separation are adopted, and iron ore concentrate which contains more than 63% of iron and has the recycling rate larger than 72% is obtained from the magnetite flotation tailings containing 28%-32% of iron. Then total tailings in an iron recycling process serve as rare earth flotation materials, sodium polyphosphate or sodium hexametaphosphate serves as pulp dispersing agents, 2-hydroxy3-naphthyl mevalonic acid or salicylhydroxami acid and alkyl hydroximic acid in a mass ratio of 6-8:1 serve as rare earth collecting agents, water glass serves as efficient flotation combination reagents of pH regulators and inhibitor, the dispersing state of pulp micro-fine particle minerals is well controlled, the rare earth separation process with once coarse separation and three-time fine separation is adopted, rare earth ore concentrate which contains more than 53% of rare earth and has the recovery rate larger than 47% is obtained from the tailings containing 5-7% of rare earth, and effective separation of rare earth minerals and gangue minerals is achieved.

The present disclosure describes methods for treating or preventing Type 1 diabetes mellitus in juveniles, particularly in juveniles newly diagnosed with Type 1 diabetes. This prevention or treatment of Type 1 diabetes is achieved by administering one or more therapeutic agents to a juvenile in need, wherein the therapeutic agent is, for example, a competitive inhibitor of mevalonate synthesis, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, or an inducer of AMP protein kinase (AMPK) activity. In certain embodiments, juveniles with Type 1 diabetes are treated with an HMG-CoA reductase inhibitor such as a statin, thereby decreasing the destruction of islet cells, or maintaining endogenous insulin production, in the juvenile.

The present invention provides a method for measuring the concentration of an analyte in a test solution wherein the analyte is mevalonic acid and/or 3-hydroxymethylglutaryl coenzyme A, comprising the following steps (p) and (q): (p) a step of allowing an enzyme that catalyzes a reaction represented by Reaction Formula 1 and an enzyme that catalyzes a reaction represented by Reaction Formula 2 to act on a test solution containing mevalonic acid and/or 3-hydroxymethylglutaryl coenzyme A in the presence of a hydrogen acceptor X, a hydrogen donor Y, and coenzyme A; and (q) a step of measuring an amount of: a reduced hydrogen acceptor X that is produced; or an oxidized hydrogen donor Y that is produced; or a hydrogen acceptor X that is decreased; or a hydrogen donor Y that is decreased, wherein the hydrogen donor Y and the reduced hydrogen acceptor X are not the same.

The invention discloses a method for positioning and synthesizing terpenoids by means of the Yarrowia lipolytica way. The method comprises the steps that an acetoacetyl coenzyme A thiolase, HMG-CoA synthetase and HMG-CoA reductase in the synthetic route of mevalonic acid in Yarrowia lipolytica are over-expressed and positioned to the peroxisome, and engineering bacteria MP1 are obtained; on the basis of the engineering bacteria MP1, the alpha-farnesene synthesis way is expressed, and engineering bacteria FP1 are obtained; or, the beta-carotene synthesis way is expressed, and engineering bacteria CP1 are obtained; or, the linalool synthesis way is expressed, engineering bacteria LP1 are obtained; the bacteria FP1 or CP1 or LP1 can synthesize the terpenoids under the aerobatic condition by means of a culture medium containing fatty acid or grease, and the yield of the synthesized terpenoids is higher compared with a traditional method. According to the method, fatty acid, grease and cheap food waste oil can be used for generating mevalonic acid downstream terpenoids, and the considerable application prospect and the economic value are achieved.

The invention discloses a method for constructing a high-yield sclareol engineering strain by a synthetic biology methdo, and an application thereof. The construction method for the strain relates to express plant sourced key enzymes for synthesizing sclareol, wherein the key enzymes comprise a pyrophosphoric acid ladanum enediol ester synthase and a sclareol synthase; and overexpress a combination of one or more yeast endogenous enzyme-based genes, wherein the enzyme-based genes comprise a key enzyme of a mevalonic acid approach-(hydroxymethyl) coenzyme A reductase, and two enzymes of an isopentenylpyrophosphate approach-a farnesyl pyrophosphate synthase and a geranylgeranyl diphosphate synthase. The method can efficiently produce sclareol, with a shake flask fermentation level reaches 9 mg/l, and has industrial application prospects.

The invention discloses a terpenoid synthase for producing nerolidol and application thereof, and belongs to the field of synthetic biology. Terpene synthase TPF09930 for producing the nerolidol is provided, a nucleotide sequence of the terpene synthase TPF09930 is as shown in SEQIDNO:2, the terpene synthase TPF09930 is combined with mevalonic acid pathway related genes to construct a strain for producing the nerolidol. By overexpression of Escherichia coli XL1 blue-derived atoB gene or idi gene of mevalonic acid pathway, catalytic substrate Farnesyl pyrophosphate can be synthesized in large scale, and producing of the nerolidol can be further promoted. The terpene synthase has specificity and high efficiency, can improve the nerolidol yield, greatly overcomes the defects of a large amount of raw materials and a low nerolidol yield, reduces study cost, and ensures greenness and environmental friendliness.

Microorganisms for the production of high-value chemicals from free fatty acids are provided. The microorganisms comprise genetic mutations that alter fatty acid metabolism. The genetic mutations include a mutation or deletion of a fadR gene in which the FadR enzyme activity is partially or substantially eliminated and a mutation in an atoC gene that provides overexpression of the microorganism's ato operon. Methods of using the microorganisms to produce high-value chemicals are also provided. The high-value chemicals include ethanol, methyl acetate, succinate, gamma-butyrolactone, 1,4-butanediol, acetone, iso-propanol, butyrate, butanol, mevalonate, propionate, ethanolamine and 1,2-propanediol.