Inhibitor of suv39h1 histone methyltransferase for use in cancer combination therapy
US-2024216388-A1 · Jul 4, 2024 · US
US9834760B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9834760-B2 |
| Application number | US-200913132765-A |
| Country | US |
| Kind code | B2 |
| Filing date | Dec 1, 2009 |
| Priority date | Dec 3, 2008 |
| Publication date | Dec 5, 2017 |
| Grant date | Dec 5, 2017 |
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According to the invention, there is provided barley-derived beverages characterized by notably reduced levels of both dimethyl sulfide (DMS) and/or its precursor S-methyl-L-methionine (SMM), or lacking said compounds. In addition, the invention relates to methods for producing the above-mentioned beverages—and also to barley plants useful in the preparation of such beverages, as well as other plant products prepared from said plants. Utilization of the invention clears the way for making improved production procedures of beverages with improved taste profiles, and promises also for notable reductions in the thermal energy input for production of beer.
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The invention claimed is: 1. A barley plant, or part thereof, wherein the barley plant carries a mutation in the gene encoding methionine-S-methyltransferase (MMT) that causes a total loss of MMT function. 2. The barley plant, or part thereof, according to claim 1 , wherein the mutation is within a splice site of the gene encoding MMT. 3. The barley plant, or part thereof, according to claim 1 , wherein the mutation in the gene encoding MMT is a G to A mutation of base 3076 of SEQ ID NO:3 or a G to A mutation of base 1462 of SEQ ID NO:16. 4. The barley plant or a part thereof according to claim 1 , wherein the mutation results in a gene encoding a truncated form of MMT comprising an N-terminal fragment of wild-type MMT and optionally additional C-terminal sequences not found in wild-type MMT, wherein said N-terminal fragment comprises at the most the 500 N terminal amino acid residues of SEQ ID NO:6. 5. The barley plant, or a part thereof, according to claim 1 , wherein said plant is selected from the group consisting of plants designated “Barley, Hordeum vulgare : Line 8063” deposited at ATCC 13 Oct. 2008 with the designation PTA-9543, and progeny plants thereof. 6. A plant product comprising a processed barley plant or part thereof, wherein said barley plant or part thereof is the barley plant or part thereof according to claim 1 . 7. The plant product according to claim 6 , wherein the plant product is a malt composition comprising a processed barley plant, or part thereof, wherein said barley plant carries the mutation in the gene encoding methionine-S-methyltransferase (MMT) that causes a total loss of MMT function. 8. The malt composition according to claim 7 , wherein the malt composition is milled malt. 9. The plant product according to claim 6 , wherein the plant product is a wort composition prepared using the barley plant, or part thereof, wherein the barley plant carries the mutation in the gene encoding methionine-S-methyltransferase (MMT) that causes a total loss of MMT function, or using a malt composition prepared from said barley plant or part thereof, or mixtures thereof. 10. The plant product according to claim 6 , wherein the plant product is selected from the group consisting of barley syrups, malt syrups, barley extracts and malt extracts. 11. A method of producing a beverage containing less than 20 ppb DMS, said method comprising the steps of: (i) preparing a composition comprising a barley plant or part thereof, according to claim 1 ; and (ii) processing the composition of (i) into a beverage; thereby obtaining a beverage containing less than 20 ppb DMS. 12. A method of producing a malt composition comprising at the most 200 ppb free DMS, said method comprising the steps of: (i) providing kernels of a barley plant according to claim 1 ; (ii) steeping said kernels; (iii) germinating the steeped kernels under predetermined conditions; and (iv) treating germinated kernels with heat; thereby producing a malt composition comprising at the most 200 ppb free DMS. 13. The barley plant or part thereof according to claim 1 , wherein the barley plant carries: (i) the mutation in the gene encoding MMT, causing total loss of MMT activity; and (ii) a mutation in the gene encoding lipoxygenase 1, causing a total loss of lipoxygenase 1 activity. 14. The barley plant, or part thereof according to claim 13 , wherein the mutation in the gene encoding MMT is a G to A mutation of base 3076 of SEQ ID NO:3 or a G to A mutation of base 1462 of SEQ ID NO:16. 15. The plant product according to claim 6 prepared from a barley plant, or part thereof, wherein the barley plant carries: (i) the mutation in the gene encoding MMT, causing total loss of MMT activity; and (ii) a mutation in the gene encoding lipoxygenase 1, causing a total loss of lipoxygenase 1 activity. 16. The plant product according to claim 15 , wherein the plant product is a beverage. 17. The plant product according to claim 15 , wherein the beverage is beer. 18. A beverage prepared from a barley plant according to claim 1 or a part of said plant, wherein said beverage contains a level of dimethyl sulfide (DMS) below 20 ppb. 19. The beverage according to claim 18 , wherein said beverage is a malt beverage. 20. The beverage according to claim 18 , wherein the beverage is beer. 21. The beverage according to claim 18 , wherein the beverage contains less than 15 ppb DMS. 22. The beverage according to claim 18 , wherein the beverage contains less than 20 ppb, S methyl-1-methionine (SMM). 23. The beverage according to claim 18 , wherein the beverage is prepared from a barley plant, or a part thereof, wherein the mutation in the gene encoding MMT is a G to A mutation of base 3076 of SEQ ID NO:3 or a G to A mutation of base 1462 of SEQ ID NO:16. 24. The beverage according to claim 18 , wherein the beverage contains no detectable DMS. 25. The beverage according to claim 18 , wherein the beverage contains no detectable S-methyl-1-methionine (SMM). 26. A method of preparing a barley plant carrying a mutation in the gene encoding MMT, causing total loss of MMT activity, comprising the steps of: (i) mutagenizing one or more of barley plants, barley kernels, barley embryos, barley cells, or barley tissue, thereby obtaining generation M0 barley; (ii) propagating said generation M0 barley for at least 2 generations, thereby obtaining generation Mx barley plants, wherein x is an integer ≧2; (iii) obtaining one or more samples from said Mx barley plants; (iv) determining the level of SMM in said one or more samples; (v) selecting one or more plants with no detectable SMM activity; (vi) sequencing at least part of the MMT gene from the one or more plants of step (v); and (vii) selecting one or more plants carrying at least one mutation in the MMT gene; thereby obtaining at least one barley plant carrying at least one mutation in the gene encoding MMT, wherein said barley plant has a total loss of MMT activity.
Use of specific genetic variants of barley or other sources of fermentable carbohydrates for beer brewing · CPC title
Methyltransferases (general) (2.1.1.) · CPC title
involving biosynthetic or metabolic pathways, i.e. metabolic engineering, e.g. nicotine, caffeine · CPC title
Processes specially adapted for making special kinds of beer · CPC title
Preparation of malt extract or of special kinds of malt, e.g. caramel, black malt (malt products for use as foodstuffs A23L) · CPC title
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