Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing oxygen-containing organic compound
Reexamination Certificate
2002-02-05
2003-06-24
Richter, Juhann (Department: 1621)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing oxygen-containing organic compound
C430S136000, C430S141000, C562S579000, C562S598000
Reexamination Certificate
active
06582943
ABSTRACT:
FIELD OF THE INVENTION
This invention is a process to produce 2-hydroxyisobutyric acid using an enzyme catalyst. More specifically, the invention pertains to production of 2-hydroxyisobutyric acid from acetone cyanohydrin using a catalyst having
Acidovorax facilis
72W nitrilase activity, or having the combined nitrile hydratase and amidase activities of
Comamonas testosteroni
5-MGAM-4D or of
Comamonas testosteroni
22-1. The 2-hydroxyisobutyric acid is used as an intermediate to produce methacrylic acid.
BACKGROUND OF THE INVENTION
Methacrylic acid and its esters are widely used to produce acrylic sheet, molding products, coatings, and impact modifiers. It is also used in such products as detergent builders, rheology modifiers, oil additives, solventless inks, paints, and polishes. Several processes to manufacture methacrylic acid exist, but the hydrolysis of methacrylamide sulfate (produced from acetone cyanohydrin) accounts for the majority of current commercial production worldwide (W. Bauer, Jr. “Methacrylic Acid and Derivatives” in: Ullmann's Encyclopedia of Industrial Chemistry, 5
th
Ed.; Eds: B. Elvers, S. Hawkins, G. Schulz; VCH, New York, 1990; vol. A 16, pp 441-452; A. W. Gross, J. C. Dobson “Methacrylic Acid and Derivatives” in: Kirk-Othmer Encyclopedia of Chemical Technology, 4
th
Ed.; Eds: J. I. Kroschwitz, M. Howe-Grant; John Wiley and Sons, New York, 1995; vol.16, pp 474-506). In this method, approximately 1.6 kg of sulfuric acid is required to produce 1 kg of methacrylic acid. Therefore, alternatives to eliminate sulfuric acid recycle and regeneration (and the significant energy resources required) in current commercial processes of methacrylic acid production would be highly desirable.
The chemical conversion of 2-hydroxyisobutyric acid to methacrylic acid is disclosed in U.S. Pat. Nos. 3,666,805 and 5,225,594, where 2-hydroxyisobutryic acid is dehydrated using metal oxides and hydroxides, ion exchange resins, alumina, silica, amines, phosphines, alkali metal alkoxides or carboxylates, and where the reaction temperature is typically between 160° C. and 250° C. In a preferred method (U.S. Pat. No. 5,225,594), 2-hydroxyisobutyric acid and sodium hydroxide were reacted at 185° C. to 195° C. under vacuum (300 torr) with stirring, resulting in a 97.1% conversion of 2-hydroxyisobutyric acid, and a 96% yield of methacrylic acid.
An alternative route for methacrylic acid production is hydrolysis of acetone cyanohydrin to 2-hydroxyisobutyric acid using a microbial or enzyme catalyst, followed by dehydration of the 2-hydroxyisobutyric acid to produce methacrylic acid. Various methods for the microbial or enzymatic hydrolysis of &agr;-hydroxynitriles to the corresponding &agr;-hydroxyacids are known. Examples of &agr;-hydroxyacids produced by these methods include glycolic acid, lactic acid, 2-hydroxyisobutyric acid, 2-hydroxy-2-hydroxyphenyl propionic acid, mandelic acid, 2-hydroxy-3,3-dimethyl-4-butyrolactone, and 4-methylthiobutyric acid.
Microorganisms capable of catalyzing hydrolysis of &agr;-hydroxynitriles include those belonging to the genera Nocardia, Bacillus, Brevibacterium, Aureobacterium, Pseudomonas, Caseobacter, Alcaligenes, Acinetobacter, Enterobacter, Arthrobacter, Escherichia, Micrococcus, Streptomyces, Flavobacterium, Aeromonas, Mycoplana, Cellulomonas, Erwinia, Candida, Bacteridium, Aspergillus, Penicillium, Cochliobolus, Fusarium, Rhodopseudomonas, Rhodococcus, Corynebacterium, Microbacterium, Obsumbacterium, and Gordona. (JP-A-4-99495, JP-A-4-99496 and JP-A-4-218385 corresponding to U.S. Pat. No. 5,223,416; JP-A-4-99497 corresponding to U.S. Pat. No. 5,234,826; JP-A-5-95795 corresponding to U.S. Pat. No. 5,296,373; JP-A-5-21987; JP-A-5-192189 corresponding to U.S. Pat. No. 5,326,702; JP-A-6-237789 corresponding to EP-A-0610048; JP-A-6-284899 corresponding to EP-A-0610049; J P-A-7-213296 corresponding to U.S. Pat. No. 5,508,181.)
Most known methods referenced above for preparing &agr;-hydroxyacids from the corresponding &agr;-hydroxynitriles using enzyme catalysts do not produce and accumulate a product at a sufficiently high concentration to meet commercial needs. This is frequently a result of enzyme inactivation early in the reaction period. For instance, U.S. Pat. No. 5,756,306 teaches that “When an &agr;-hydroxynitrile is enzymatically hydrolyzed or hydrated using nitrilase or nitrile hydratase to produce an &agr;-hydroxyacid or &agr;-hydroxyamide, a problem occurs in that the enzyme is inactivated within a short period of time. It is therefore difficult to obtain the &agr;-hydroxyacid or &agr;-hydroxyamide in high concentration and high yield.” (col. 1, lines 49-54).
U.S. Pat. No. 6,037,155 teaches that low accumulation of &agr;-hydroxyacid products is related to enzyme inactivation within a short time after start of the reaction. Enzymatic activity is inhibited in the presence of hydrogen cyanide (Asano et al.,
Agricultural Biological Chemistry
, 46:1164-1165 (1982) (renamed
Bioscience, Biotechnology
&
Biochemistry
as of January 1992)) which is generated in the partial disassociation of &agr;-hydroxynitriles in water, together with the corresponding aldehyde or ketone (Mowry,
Chemical Reviews,
42:189-284 (1948)). With respect to the production of 2-hydroxyisobutyric acid, acetone cyanohydrin is known to reversibly disassociate to hydrogen cyanide and acetone in water (Stewart et al.,
J. Am. Chem. Soc
. 62:3281-5 (1940)), and the resulting hydrogen cyanide can inactivate enzyme activity.
A method for preparing lactic acid, glycolic acid, and 2-hydroxyisobutyric acid by using a microorganism belonging to Corynebacterium spp. is disclosed in Japanese Patent Laid-open No. Sho 61-56086. 2-Hydroxyisobutyric acid has also been produced from acetone cyanohydrin using microorganisms belonging to the genus Rhodococcus, Pseudomonas, Arthrobacter, or Brevibacterium (JP 04040897 A2), and Achromobacter (JP 06237776 A2). The efficiency of 2-hydroxyisobutyric acid production when using
Rhodococcus rhodochrous
(ATCC 19140) was improved by adding acetone at a concentration of 0.5-50 wt % to the reaction mixture (JP 05219969 A2), presumably by sequestration of hydrogen cyanide.
As illustrated above, developing an industrial process using microbial catalysts having nitrilase or nitrile hydratase/amidase activities to efficiently manufacture 2-hydroxyisobutyric acid has proved difficult. The presence of cyanide ion in the reaction mixtures can inactivate or inhibit enzyme activity.
The problem to be solved remains the lack of facile microbial catalysts to convert acetone cyanohydrin to 2-hydroxyisobutyric acid in a process characterized by high selectivity and with high conversions, and with the added advantages of low temperature processing and low waste production relative to previously known methods.
SUMMARY OF THE INVENTION
The invention provides a process for preparing 2-hydroxyisobutyric acid from acetone cyanohydrin with high specificity and at high conversion. The invention includes the steps of (a) contacting acetone cyanohydrin in a suitable aqueous reaction mixture with a catalyst characterized by nitrilase activity (EC 3.5.5.7), or by nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities; and (b) isolating the 2-hydroxyisobutyric acid produced in (a) as the acid or corresponding salt. Methacrylic acid is obtained by dehydrating the acid produced in (a); and isolating the acid or corresponding salt. These reactions are shown below.
The invention uses enzyme catalysts (including those derived from the biological deposits indicated herein) in the form of intact microbial cells, permeabilized microbial cells, one or more cell components of a microbial cell extract, and partially purified enzyme(s), or purified enzyme(s). In any form, the enzyme catalysts may be immobilized in or on a soluble or insoluble support.
BRIEF DESCRIPTION OF THE BIOLOGICAL DEPOSITS
Applicants have made the following biological deposits under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for
Chauhan Sarita
DiCosimo Robert
Fallon Robert
Gavagan John
Manzer Leo Ernest
E. I. du Pont de Nemours and Company
Richter Juhann
Zucker Paul A.
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