PROCESS FOR PREPARING METHACRYLIC ACID OR METHACRYLIC ESTERS

• US 20100291644A1
• Filed: 05/30/2008
• Published: 11/18/2010
• Est. Priority Date: 06/02/2006
• Status: Active Grant

• Current Assignee: Evonik Rã¶Hm GmbH (Rag-Stiftung)
• Original Assignee: Evonik Rã¶Hm GmbH (Rag-Stiftung)
• Inventors: May, Alexander, Alber, Birgit, Fuchs, Georg, Buchholz, Stefan, Eggeling, Lothar, Siegert, Hermann, Poetter, Markus, Marx, Achim
• Granted Patent: US 9,234,218 B2
• Time in Patent Office: Days
• US Class Current: 435/135
• CPC Class Codes: C08F 120/06 Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
• CPC Class Codes: C08F 120/10 Esters
• CPC Class Codes: C12N 9/0008 acting on the aldehyde or oxo group of donors (1.2)
• CPC Class Codes: C12N 9/001 acting on the CH-CH group of donors (1.3)
• CPC Class Codes: C12N 9/1096 transferring nitrogenous groups (2.6)
• CPC Class Codes: C12N 9/16 acting on ester bonds (3.1)
• CPC Class Codes: C12N 9/88 Lyases (4.)
• CPC Class Codes: C12P 7/40 containing a carboxyl group including Peroxycarboxylic acids
• CPC Class Codes: C12P 7/42 Hydroxy-carboxylic acids
• CPC Class Codes: C12P 7/52 Propionic acid; Butyric acids
• CPC Class Codes: C12P 7/625 Polyesters of hydroxy carboxylic acids
• CPC Class Codes: C12Y 102/04004 3-Methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) (1.2.4.4), i.e. branched-chain-alpha-ketoacid dehydrogenase
• CPC Class Codes: C12Y 103/99012 2-Methylacyl-CoA dehydrogenase (1.3.99.12)
• CPC Class Codes: C12Y 206/01042 Branched-chain-amino-acid transaminase (2.6.1.42)
• CPC Class Codes: C12Y 301/02004 3-Hydroxyisobutyryl-CoA hydrolase (3.1.2.4)
• CPC Class Codes: C12Y 402/01017 Enoyl-CoA hydratase (4.2.1.17), i.e. crotonase

Abstract

The present invention relates to a process for the preparation of methacrylic acid or methacrylic esters, comprising the process steps of

• IA) preparation of 3-hydroxyisobutyric acid by a process comprising the process step of bringing a cell which has been genetically modified in comparison with its wild type in such a way that it is capable of forming more 3-hydroxyisobutyric acid, or polyhydroxyalkanoates based on 3-hydroxyisobutyric acid in comparison with its wild type, into contact with a nutrient medium comprising, as carbon source, carbohydrates, glycerol, carbon dioxide, methanol, L-valine or L-glutamate under conditions under which 3-hydroxyisobutyric acid or polyhydroxyalkanoates based on 3-hydroxyisobutyric acid are formed from the carbon source, if appropriate, isolation of the 3-hydroxyisobutyric acid from the nutrient medium and also, if appropriate, neutralization of the 3-hydroxyisobutyric acid,
• IB) dehydration of the 3-hydroxyisobutyric acid with formation of methacrylic acid and also, where appropriate, esterification methacrylic acid.

The invention also relates to a process for the preparation of polymethacrylic acid or polymethacrylic esters.

Claims

1. A process for preparing a methacrylic acid or a methacrylic ester, comprising

IA) preparing a 3-hydroxyisobutyric acid by a process comprising bringing a cell which is genetically modified in comparison with a wild type of the cell, wherein the cell is capable of forming more 3-hydroxyisobutyric acid, or polyhydroxyalkanoate comprising 3 hydroxyisobutyric acid, into contact with a nutrient medium comprising, as carbon source, carbohydrate, glycerol, carbon dioxide, methane, methanol, L-valine or L-glutamate under a condition wherein a 3-hydroxyisobutyric acid or polyhydroxyalkanoate comprising 3-hydroxyisobutyric acid is obtained from the carbon source, optionally isolating the 3-hydroxyisobutyric acid from the nutrient medium and optionally neutralizing the 3-hydroxyisobutyric acid, and

IB) dehydrating the 3-hydroxyisobutyric acid, forming a methacrylic acid and optionally esterifying the methacrylic acid.

2. The process as claimed in claim 1, wherein forming the 3-hydroxyisobutyric acid or polyhydroxyalkanoate comprising 3-hydroxyisobutyric acid comprises forming methylmalonate semialdehyde as precursor.

3. The process as claimed in claim 2, wherein forming the 3-hydroxyisobutyric acid or polyhydroxyalkanoate comprising 3-hydroxyisobutyric acid comprises forming succinyl-coenzyme A as intermediate.

4. The process as claimed in claim 3, wherein the cell has an activity of an enzyme E₁, wherein the activity catalyzes conversion of succinyl-coenzyme A into methylmalonyl-coenzyme A, and is increased in comparison with the wild type of the cell.

5. The process as claimed in claim 4, wherein the enzyme E₁ is a methylmalonyl-coenzyme A mutase (EC 5.4.99.2).

6. The process as claimed in claim 3, wherein the cell has an activity of at least one of following enzymes E₂ to E₄, wherein the activity is increased in comparison with the wild type of the cell:

an enzyme E₂, which catalyzes the conversion of methylmalonyl-coenzyme A into methyl malonate;

an enzyme E₃, which catalyzes the conversion of methyl malonate into methylmalonate semialdehyde;

an enzyme E₄ which catalyzes the conversion of methylmalonate semialdehyde into 3-hydroxyisobutyrate.

7. The process as claimed in claim 6, wherein

E₂ is a methylmalonyl-coenzyme A hydrolase (EC 3.1.2.17),

E₃ is an aldehyde dehydrogenase (EC 1.2.1.3) or an aldehyde oxidase (EC 1.2.3.1) and

E₄ is a 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31) or a 3-hydroxyacyl-coenzyme A dehydrogenase (EC 1.1.1.35).

8. The process as claimed in claim 3, wherein the cell has an activity of at least one of following enzymes E₄, E₅, E₆ and E₇ wherein the activity is increased in comparison with the wild type of the cell:

an enzyme E₆, which catalyzes the conversion of (R) methylmalonyl-coenzyme A into (S) methylmalonyl-coenzyme A;

an enzyme E₇, which catalyzes the conversion of (S) methylmalonyl-coenzyme A into propionyl-coenzyme A;

an enzyme E₅, which catalyzes the conversion of propionyl-coenzyme A into methylmalonate semialdehyde; and

an enzyme E₄, which catalyzes the conversion of methylmalonate semialdehyde into 3-hydroxyisobutyric acid.

9. The process as claimed in claim 8, wherein

E₆ is a methylmalonyl-coenzyme A epimerase (EC 5.1.99.1)

E₇ is a methylmalonyl-coenzyme A decarboxylase (EC 4.1.1.41),

E₅ is a methylmalonate-semialdehyde dehydrogenase (EC 1.2.1.27), and

E₄ is a 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31) or a 3-hydroxyacyl-coenzyme A dehydrogenase (EC 1.1.1.35).

10. The process as claimed in claim 3, wherein the cell has an activity of at least one of following enzymes E₄, E₅ and E₇ wherein the activity is increased in comparison with the wild type of the cell:

an enzyme E₇, which catalyzes the conversion of methylmalonyl-coenzyme A into propionyl-coenzyme A;

an enzyme E₅, which catalyzes the conversion of propionyl-coenzyme A into methylmalonate semialdehyde;

an enzyme E₄, which catalyzes the conversion of methylmalonate semialdehyde into 3-hydroxyisobutyric acid.

11. The process as claimed in claim 10, wherein

E₇ is a methylmalonyl-coenzyme A decarboxylase (EC 4.1.1.41),

E₅ is a methylmalonate-semialdehyde dehydrogenase (EC 1.2.1.27), and

E₄ is a 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31) or a 3-hydroxyacyl-coenzyme A dehydrogenase (EC 1.1.1.35).

12. The process as claimed in claim 3, wherein the cell has an activity of at least one of following enzymes E₂₈ and E₄₆ wherein the activity is increased in comparison with the wild type of the cell:

an enzyme E₄₆, which catalyzes the conversion of L-glutamate into 2-oxoglutarate;

an enzyme E₂₈, which catalyzes the conversion of 2-octoglutarate into succinyl-coenzyme A.

13. The process as claimed in claim 12, wherein

E₄₆ is a glutamate synthase (EC 1.4.1.13 or EC 1.4.1.14), a glutamate dehydrogenase (EC 1.4.1.2, EC 1.4.1.3 or EC 1.4.1.4) or an aspartate transaminase (EC 2.6.1.1 or EC 2.6.1.2) and

E₂₈ is a 2-oxoglutarate synthase (EC 1.2.7.3).

14. The process as claimed in claim 2, wherein forming 3-hydroxyisobutyric acid or polyhydroxyalkanoate comprising 3-hydroxyisobutyric acid comprises forming propionyl-coenzyme A as intermediate.

15. The process as claimed in claim 14, wherein the cell has an activity of at least one of following enzymes E₄, E₅ and E₄₇ to E₅₂ wherein the activity is increased in comparison with the wild type of the cell:

an enzyme E₄₇, which catalyzes the conversion of acetyl-coenzyme A into malonyl-coenzyme A;

an enzyme E₄₈, which catalyzes the conversion of malonyl-coenzyme A into malonate semialdehyde;

an enzyme E₄₉, which catalyzes the conversion of malonate semialdehyde into 3-hydroxypropionate;

an enzyme E₅₀, which catalyzes the conversion of 3-hydroxypropionate into 3-hydroxypropionyl-coenzyme A;

an enzyme B₅₁, which catalyzes the conversion of 3-hydroxypropionyl-coenzyme A into acryloyl-coenzyme A;

an enzyme E₅₂, which catalyzes the conversion of acryloyl-coenzyme A into propionyl-coenzyme A;

an enzyme E₅, which catalyzes the conversion of propionyl-coenzyme A into methylmalonate semialdehyde;

an enzyme E₄, which catalyzes the conversion of methylmalonate semialdehyde into 3-hydroxyisobutyrate.

16. The process as claimed in claim 15, wherein

E₄ is a 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31) or a 3-hydroxyacyl-coenzyme A dehydrogenase (EC 1.1.1.35),

E₅ is a methylmalonate-semialdehyde dehydrogenase (EC 1.2.1.27),

E₄₇ is a malonyl-coenzyme A decarboxylase (EC 4.1.1.9), a malonate coenzyme A transferase (EC 2.8.3.3), a methylmalonyl-coenzyme A carboxy-transferase (EC 2.1.3.1) or an acetyl-coenzyme A carboxylase (EC 6.4.1.2),

E₄₈ is a malonate-semialdehyde dehydrogenase (EC 1.2.1.18),

E₄₉ is a 3-hydroxypropionate dehydrogenase (EC 1.1.1.59),

E₅₀ is a 3-hydroxyisobutyryl-coenzyme A hydrolase (EC 3.1.2.4),

E₅₁ is an enoyl-coenzyme A hydratase (EC 4.2.1.17) and

E₅₂ is an acyl-coenzyme A dehydrogenase (EC 1.3.99.3).

17. The process as claimed in claim 2, wherein forming the 3-hydroxyisobutyric acid or polyhydroxyalkanoate comprising 3 hydroxyisobutyric acid comprises forming acryloyl-coenzyme A as intermediate.

18. The process as claimed in claim 17, where the cell has an activity of at least one of following enzymes E₂ to E₄, E₅₆, E₇₂ and E₇₃ wherein the activity increased in comparison with the wild type of the cell:

an enzyme E₇₂, which catalyzes the conversion of beta-alanine into beta-alanyl-coenzyme A,

an enzyme E₇₃, which catalyzes the conversion of beta-alanyl-coenzyme A into acrylyl-coenzyme A,

an enzyme E₅₆, which catalyzes the conversion of acrylyl-coenzyme A into methylmalonyl-coenzyme A,

an enzyme E₂, which catalyzes the conversion of methylmalonyl-coenzyme A into methyl malonate;

an enzyme E₃, which catalyzes the conversion of methyl malonate into methylmalonate semialdehyde;

an enzyme E₄, which catalyzes the conversion of methylmalonate semialdehyde into 3-hydroxyisobutyric acid.

19. The process as claimed in claim 18, wherein

E₇₂ is a coenzyme A transferase (EC 2.8.3.1) or coenzyme A synthetase, preferably a coenzyme A transferase,

E₇₃ is a beta-alanyl-coenzyme A ammonia-lyase (EC 4.3.1.6),

E₅₆ is a crotonyl-coenzyme A decarboxylase

E₂ is a methylmalonyl-coenzyme A hydrolase (EC 3.1.2.17),

E₃ is an aldehyde dehydrogenase (EC 1.2.1.3) or an aldehyde oxidase (EC 1.2.3.1) and

E₄ is a 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31) or a 3-hydroxyacyl-coenzyme A dehydrogenase (EC 1.1.1.35).

20. The process as claimed in claim 1, wherein forming the 3-hydroxyisobutyric acid or polyhydroxyalkanoate comprising 3-hydroxyisobutyric acid comprises forming 3-hydroxybutyryl-coenzyme A as precursor.

21. The process as claimed in claim 20, forming the 3-hydroxyisobutyric acid or polyhydroxyalkanoate comprising 3-hydroxyisobutyric acid comprises forming isobutyryl coenzyme A as intermediate.

22. The process as claimed in claim 21, where the cell has an activity of at least one of following enzymes E₇₆ to E₇₉, E₆₀, E₆₁ and E₈ wherein the activity is increased in comparison with the wild type of the cell:

an enzyme E₇₆, which catalyzes the conversion of pyruvate into 2-acetolactate;

an enzyme E₇₇, which catalyzes the conversion of 2-acetolactate into 2,3-dihydroxyisovalerate;

an enzyme E₇₈, which catalyzes the conversion of 2,3-dihydroxyisovalerate into 2-oxoisovalerate;

an enzyme E₇₉, which catalyzes the conversion of 2-oxoisovalerate into isobutyryl-coenzyme A;

an enzyme E₆₀, which catalyzes the conversion of isobutyryl-coenzyme A into methacrylyl-coenzyme A;

an enzyme E₆₁, which catalyzes the conversion of methacrylyl-coenzyme A into 3-hydroxyisobutyryl-coenzyme A;

an enzyme E₈, which catalyzes the conversion of 3-hydroxyisobutyryl-coenzyme A into 3-hydroxyisobutyrate.

23. The process as claimed in claim 22, wherein

E₈ is a 3-hydroxyisobutyryl-coenzyme A hydrolase (EC 3.1.2.4),

E₇₆ is an acetolactate synthase (EC 2.2.1.6),

E₇₇ is a dihydroxyisovalerate dehydrogenase (EC 1.1.1.86),

E₇₈ is a 2,3-dihydroxyisovalerate dehydratase (EC 4.2.1.9),

E₇₉ is a 2-oxoisovalerate dehydrogenase (EC 1.2.1.25 or EC 1.2.4.4),

E₆₀ is an acyl-coenzyme A dehydrogenase (EC 1.3.99.3), a butyryl-coenzyme A dehydrogenase (EC 1.3.99.2) or a 2-methylacyl-coenzyme A dehydrogenase (EC 1.3.99.12), and

E₆₁ is an enoyl-coenzyme A hydratase (EC 4.2.1.17).

24. The process as claimed in claim 21, where the cell has an activity of at least one of following enzymes E₈, E₆₀ to E₆₁ and E₇₉ to E₈₀ wherein the activity is increased in comparison with the wild type of the cell:

an enzyme E₈₀, which catalyzes the conversion of L-valine into 2-oxoisovalerate;

an enzyme E₇₉, which catalyzes the conversion of 2-oxoisovalerate into isobutyryl-coenzyme A;

an enzyme E₆₀, which catalyzes the conversion of isobutyryl-coenzyme A into methacrylyl-coenzyme A;

an enzyme E₆₁, which catalyzes the conversion of methacrylyl-coenzyme A into 3-hydroxyisobutyryl-coenzyme A;

an enzyme E₈, which catalyzes the conversion of 3-hydroxyisobutyryl-coenzyme A into 3-hydroxyisobutyrate.

25. The process as claimed in claim 24, wherein

E₈ is a 3-hydroxyisobutyryl-coenzyme A hydrolase (EC 3.1.2.4),

E₆₀ is an acyl-coenzyme A dehydrogenase (EC 1.3.99.3), a butyryl-coenzyme A dehydrogenase (EC 1.3.99.2) or a 2-methylacyl-coenzyme A dehydrogenase (EC 1.3.99.12),

E₆₁ is an enoyl-coenzyme A hydratase (EC 4.2.1.17),

E₇₉ is a 2-oxoisovalerate dehydrogenase (EC 1.2.1.25 or EC 1.2.4.4), and

E₈₀ is an amino acid transferase (EC 2.6.1.42).

27. A process of preparing polymethacrylic acid or polymethacrylic ester, comprising

IIIA) preparing a methacrylic acid by the process according to claim 1,

IIIB) carrying out free-radical polymerization of the methacrylic acid, and optionally esterifying at least in part the carboxyl groups of the methacrylic acid or the carboxylate group of the methacrylate before or after the free-radical polymerization reaction.

26. (canceled)