86 results about "Mevalonate pathway" patented technology

The present invention provides methods of producing an isoprenoid or an isoprenoid precursor in a genetically modified host cell. The methods generally involve modulating the level of hydroxymethylglutaryl-CoA (HMG-CoA) in the cell, such that the level of HMG-CoA is not toxic to the cell and / or does not substantially inhibit cell growth, but is maintained at a level that provides for high-level production of mevalonate, IPP, and other downstream products of an isoprenoid or isoprenoid pathway, e.g., polyprenyl diphosphates and isoprenoid compounds. The present invention further provides genetically modified host cells that are suitable for use in a subject method. The present invention further provides recombinant nucleic acid constructs for use in generating a subject genetically modified host cell, including recombinant nucleic acid constructs comprising nucleotide sequences encoding one or more mevalonate pathway enzymes, and recombinant vectors (e.g., recombinant expression vectors) comprising same. The present invention further provides methods for identifying nucleic acids that encode HMG-CoA reductase (HMGR) variants that provide for relief of HMG-CoA accumulation-induced toxicity. The present invention further provides methods for identifying agents that reduce intracellular accumulation of HMG-CoA.

The invention features methods for producing isoprene from cultured cells using a feedback-resistant mevalonate kinase polypeptide, such as an archaeal mevalonate kinase polypeptide. The resulting isoprene compositions may have increased yields and / or purity of isoprene.

Isolated polynucleotides encoding polypeptides having the activity of enzymes in the mevalonate pathway are provided. These sequences are useful for recombinantly producing isoprenoid compounds, such as carotenoids, in particular zeaxanthin. Expression vectors, cultured cells, and methods of making isoprenoid compounds are also provided.

Isolated polynucleotides encoding polypeptides having the activity of enzymes in the mevalonate pathway are provided. These sequences are useful for recombinantly producing isoprenoid compounds, such as carotenoids, in particular zeaxanthin. Expression vectors, cultured cells, and methods of making isoprenoid compounds are also provided.

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 present invention provides genetically modified eukaryotic host cells exhibiting increased activity levels of one or more enzymes that generate precursors to be utilized by the mevalonate pathway enzymes, increased activity levels of one or more mevalonate pathway enzymes, prenyl transferase, and / or decreased levels of squalene synthase activity; such cells are useful for producing isoprenoid compounds. The present invention provides genetically modified eukaryotic host cells that produce higher levels of acetyl-CoA than a control cell; such cells are useful for producing a variety of products, including isoprenoid compounds. Methods are provided for the production of an isoprenoid compound or an isoprenoid precursor in a subject genetically modified eukaryotic host cell. The methods generally involve culturing a subject genetically modified host cell under conditions that promote production of high levels of an isoprenoid or isoprenoid precursor compound.

The present invention provides a process for producing isoprenoid compounds or proteins encoded by DNA using DNA that contains one or more of the DNA encoding proteins having activity to improve efficiency in the biosynthesis of isoprenoid compounds effective in pharmaceuticals for cardiac diseases, osteoporosis, homeostasis, prevention of cancer, and immunopotentiation, health food and anti-fouling paint products against barnacles; the DNA; the protein; and a method for screening a substance with antibiotic and weeding activities comprising screening a substance inhibiting enzymatic reaction on the non-mevalonate pathway.

The invention discloses a bacterial strain for producing lycopene and an application of the bacterial strain, and belongs to the field of synthetic biology. The bacterial strain for producing lycopene contains a mevalonate pathway and a related gene which is synthetized by the lycopene optimized by a codon; and the synthetic gene sequence of the lycopene optimized by the codon is shown in SEQ ID NO.1-3. The bacterial strain can be used for producing the lycopene; and a seed solution of the bacterial strain is inoculated into a culture medium containing a carbon source to carry out prokaryotic expression, so as to obtain the lycopene. The gene synthetized by the lycopene is optimized by the codon or each protein of the mevalonate pathway is closer to A to B:ERG13:tHMG1:ERG12:ERG8:MVD1:Idi=1:10:2:5:5:2:5; and production of the lycopene can be further promoted. By adopting the bacterial strain, the yield of the lycopene can be greatly improved to over 1g / L; and the fermentation cycle is shortened by over 50%.

The invention discloses a high-yield s-linalool genetic engineering strain and a building method, which belong to the field of genetic engineering. Through the metabolic engineering reformation, linalool synthetase from actinidiaarguta is expressed in saccharomyces cerevisiae CEN.PK2-1 in a heterologous way, the terpene synthesis path-mevalonic acid (MVA) path carbon metabolizing flow is increased, and the high-yield s-linalool genetic engineering strain CEN. PK2 linalool is obtained. Compared with an initial strain CEN. PK2-1C, the modified genetic engineering strain CEN. PK2 linalool can metabolize and produce s-linalool, in addition, the feedback inhibition of the s-linalool is obviously reduced, the yield of the s-linalool can reach 12 mg / L, and the genetic engineering strain has good application prospects.

The invention discloses a method for preparing farnesene by using a biodiesel by-product. The method comprises the steps of purification of the biodiesel by-product, wherein the purity of the purified glycerin reaches 63.8% (w / w), building of a recombinant host cell for preparing farnesene from the purified glycerin as the raw material, wherein the recombinant host cell comprises related genes in a mevalonate pathway or deoxymutulose-5-hexose monophosphate pathway, an isopentene pyrophosphate isomerase gene, a farnesene isopentenyl pyrophosphate synthetase gene and a farnesene synthetase gene. The method also comprises fermentation of the purified glycerin as the raw material in the recombinant host cell to prepare the farnesene, wherein the concentration of the obtained farnesene is 0.025g / L; and optimum construction of the recombinant host cell capable of improving the yield of the farnesene by employing the purified glycerin as the raw material, wherein the concentration of the obtained farnesene reaches 2.9g / L, and the concentration is improved by 115 times in comparison with that before optimization.

To provide a series of techniques capable of producing isoprene from syngas or the like.Provided is a recombinant cell prepared by introducing a nucleic acid encoding isoprene synthase into a host cell having an isopentenyl diphosphate synthesis ability by a non-mevalonate pathway, wherein the nucleic acid is expressed in the host cell, and the recombinant cell is capable of producing isoprene from at least one C1 compound selected from the group consisting of carbon monoxide, carbon dioxide, formic acid, and methanol. As the host cell, a Clostridium bacterium or a Moorella bacterium is exemplified. Also provided is a method for producing isoprene using the recombinant cell.