Methods for synthesis of olefins and derivatives

Patent metadata

Field	Value
Publication number	US-9365874-B2
Application number	US-201313887140-A
Country	US
Kind code	B2
Filing date	May 3, 2013
Priority date	Aug 10, 2007
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

Abstract

The invention provides a method of producing acrylic acid. The method includes contacting fumaric acid with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylic acid per mole of fumaric acid. Also provided is an acrylate ester. The method includes contacting fumarate diester with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylate ester per mole of fumarate diester. An integrated process for process for producing acrylic acid or acrylate ester is provided which couples bioproduction of fumaric acid with metathesis transformation. An acrylic acid and an acrylate ester production also is provided.

First claim

What is claimed is:

1. A non-naturally Escherichia coli comprising a set of metabolic modifications obligatorily coupling fumaric acid production to growth of said Escherichia coli , said set of metabolic modifications comprising disruption of at least one gene encoding an enzyme catalyzing reactions selected from the group consisting of:
(1) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD) and
(2) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Serine hydroxymethyl transferase (GHMT2) or an ortholog thereof, which confer stable growth-coupled production of fumaric acid.

2. A fumarate dialkyl ester production system, comprising:
(a) a vessel comprising a culture of a non-naturally Escherichia coli in nutrients and media, said non-naturally occurring Escherichia coli comprising a set of metabolic modifications obligatorily coupling fumaric acid production to growth of said microbial organism, said set of metabolic modifications comprising disruption of at least one gene encoding an enzyme catalyzing reactions selected from the group consisting of:
(1) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD) and
(2) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Serine hydroxymethyl transferase (GHMT2)
or an ortholog thereof, which confer stable growth-coupled production of fumaric acid; and

(b) a source of at least one diesterification reagent and in communication with the vessel wherein the at least one diesterification reagent is sufficient to produce fumarate dialkyl ester from said fumaric acid.

3. The production system of claim 2 , wherein said reactions encoding said metabolic modifications further comprises disruption of at least one gene selected from a set encoding enzyme reactions selected from the group consisting of reactions:
(1) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD), Acetate kinase (ACKr)
(2) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD), Glutamate dehydrogenase (GLUDy);
(3) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD), Transhydrogenase (THD2); and
(4) Fumarase (FUM), Formyltetrahydrofolate hydrolase (FTHFD), Transhydrogenase (THD2), Acetate kinase (ACKr), Phosphoglyceromutase (PGM), Phosphogluconal acotonase (PGL).

4. The production system of claim 2 , wherein said disruption comprises a deletion of at least one gene within said reaction set.

5. The production system of claim 2 , wherein said diesterification reagent is an alcohol at a 1:2 molar ratio of fumaric acid produced in culture with the alcohol under condensation reaction conditions sufficient to produce fumarate dialkyl ester and water at a 1:2 molar ratio.

6. The production system of claim 5 , further comprising an esterification catalyst.

7. The production system of claim 6 , wherein said esterification catalyst is sulfuric acid (H 2 SO 4 ) or p-toluene sulfonic acid.

8. The fumarate dialkyl ester production system of claim 2 , 5 or 7 , wherein the fumarate dialkyl ester is dibutyl fumarate.

9. The production system of claim 2 , wherein said nutrients and media comprise at least one carbon substrate selected from glucose, xylose, arabinose, galactose, mannose or fructose.

10. A process for producing an olefin, comprising: (a) culturing by fermentation in a sufficient amount of nutrients and media a microbial organism that produces a first olefin, and (b) contacting said first olefin with a sufficient amount of a disubstituted alkene in the presence of an olefin metathesis transformation catalyst to produce second, different olefin; wherein the first olefin is fumaric acid, the disubstituted alkene is 2-butene, and the second, different olefin is crotonic acid and the microbial organism that produces the first olefin is a non-naturally occurring Escherichia coli organism comprising a set of metabolic modifications obligatorily coupling fumaric acid production to growth of said Escherichia coli to produce fumaric acid, wherein said set of metabolic modifications comprises disruption of at least one gene encoding an enzyme catalyzing reactions selected from the group of consisting of:
(1) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD) and
(2) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Serine hydroxymethyl transferase (GHMT2)
or an ortholog thereof, which confer stable growth-coupled production of fumaric acid.

11. A process for producing dibutyl fumarate comprising: (a) culturing in a sufficient amount of nutrients and media a non-naturally occurring Escherichia coli organism comprising a set of metabolic modifications obligatorily coupling fumaric acid production to growth of said Escherichia coli to produce fumaric acid; and (b) performing diesterification of said fumaric acid to produce dibutyl fumarate, wherein said set of metabolic modifications comprises disruption of at least one gene encoding an enzyme catalyzing reactions selected from the group consisting of:
(1) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD) and
(2) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Serine hydroxymethyl transferase (GHMT2)
or an ortholog thereof, which confer stable growth-coupled production of fumaric acid; and
(b) at least one diesterification reagent sufficient to produce fumarate dialkyl ester from said fumaric acid.

12. The process of claim 11 , wherein performing diestesterification comprises contacting said fumaric acid with an alcohol at a 1:2 molar ratio in under condensation reaction conditions sufficient to produce dibutyl fumarate and water at a 1:2 molar ratio.

13. The process of claim 11 , wherein performing diestesterification comprises contacting said fumaric acid with a butyl alcohol and sulfuric acid —(H 2 SO 4 )— or p-toluene sulfonic acid.

14. A process comprising a) culturing by fermentation in a sufficient amount of nutrients and media a non-naturally occurring Escherichia coli that produces fumaric acid; b) esterification of said fumaric acid to provide fumarate dibutyl ester; and c) olefin metathesis of said fumarate dibutyl ester to butyl acrylate in the presence of metathesis ruthenium catalyst bearing an N-heterocyclic carbene ligand, wherein said non-naturally occurring Escherichia coli comprises a set of metabolic modifications comprising disruption of at least one gene encoding an enzyme catalyzing reactions selected from the group consisting of:
(1) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Formyltetrahydrofolate hydrolase (FTHFD) and
(2) Fumarase (FUM), Phosphogluconate dehydrogenase (PGDH), Serine hydroxymethyl transferase (GHMT2) or an ortholog thereof, which confer stable growth-coupled production of fumaric acid.

15. The method of claim 14 , wherein the metathesis ruthenium catalyst bearing an N-hetrocyclic carbine ligand is selected from the group consisting of
[1,3 bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro[(2-(1-methyleth-oxy)phenyl)methylene]ruthenium;
[1,3-bis(2-methylphenyl)-2-imidazolidinylidene]dichloro(benzylidene) (tricyclohexylphosphine)ruthenium(II);
[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(3-methyl-2-butenylidene)(tricyclohexylphosphine)ruthenium(II); and
[1,3-bis-(2,4,6 trimethylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tricyclo- hexylphosphine) ruthenium.

Assignees

• Genomatica Inc

Inventors

• Burk Mark J
• Pharkya Priti
• Van Dien Stephen J
• Burgard Anthony P
• Schilling Christophe H

Classifications

• C07C69/54

  Acrylic acid esters; Methacrylic acid esters · CPC title

• C12P7/40 Primary

  containing a carboxyl group {including Peroxycarboxylic acids} · CPC title

• C07C67/32

  Decarboxylation · CPC title

• C07C57/04

  Acrylic acid; Methacrylic acid · CPC title

• C12P7/46

  Dicarboxylic acids having four or less carbon atoms, e.g. fumaric acid, maleic acid · CPC title