AU606185B2 - Improved process for the enzymatic preparation of l-2-amino-4-methylphosphinobutyric acid - Google Patents
Improved process for the enzymatic preparation of l-2-amino-4-methylphosphinobutyric acid Download PDFInfo
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- AU606185B2 AU606185B2 AU19733/88A AU1973388A AU606185B2 AU 606185 B2 AU606185 B2 AU 606185B2 AU 19733/88 A AU19733/88 A AU 19733/88A AU 1973388 A AU1973388 A AU 1973388A AU 606185 B2 AU606185 B2 AU 606185B2
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/006—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures
- C12P41/007—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures by reactions involving acyl derivatives of racemic amines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
Cells of E. coli ATCC 11105 immobilised on chitosan are distinguished in the racemate resolution of D,L-2-amino-4-methylphosphinobutyric acid by smaller losses of activity and longer useful lives compared with immobilised acylases.
Description
L- F7 1" COMMONWEALTH OF AUSTRALIA 6 0V 8 PATENTS ACT 1952,09 COMPLETE SPECIFICATION
(ORIGINAL)
Class Int. Class Application Number: Lodged: 00 t a 0 0*0 00 0 Complete Specification Lodged: Accepted: 000I Published: *Pinority: 'I his doetin t cofaa the.
Iamecndments Mai'de nl i Section 49 and is correct for printing Related Art: 'NaJme of Applicant: 0 Address of Applicant Actual Inventor: HOECHST AKTIENGESELLSCHAFT 45 Bruningstrasse, D-623O Frankfurt/Main 80, Federal Republic of Germany DIETER WULLBRANDT and REINHOLD KELLER Address for Service: EDWD. WATERS SON.' 50 QUEEN STREET, MELBOURNE, AUSTRALIA, 3000.
Complete Specification for the invention entitled: IMPROVED PROCESS FOR THE ENZYMATIC PREPARATION OF L-2- AMINO-4-METHYLPHOSPHINOBUTYRIC ACID Thie following statement is a full description of this invention, including the best method of performing it known to ',us -I ct HOECHST AKTIENGESELLSCHAFT HOE 87/F 213 Dr.KH/AW Description Improved process for the enzymatic preparation of L-2amino-4-methylphosphinobutyric acid L-2-Amino-4-methylphosphinobutyric acid (called L-phosphinothricin or L-PTC below) or salts thereof with organic or inorganic bases or acids are, as has also been disclosed in German Offenlegungsschrift 2,939,269, the active component of the racemates which are readily accessible chemically. According to German Offenlegungsschrift 2,717,440, L-PTC has a very good and broad herbicidal activity against numerous monocotyledonous and di- S* cotyledonous, annual and perennial weeds. Since the 15 activity of L-PTC and its abovementioned derivatives is about twice that of the racemates, it was desirable to a o. develop a process which makes it possible to provide Srelatively large quantities of L-PTC in a simple manner.
0 0o 0o 20 L-PTC can be obtained by acid hydrolysis (Japanese S' Published Application 73-85,538) or enzymatic degradation (Japanese Published Application 74-31,890) of L-PTCalanylalanine, which is a microbially obtained antibiotic known from the literature.
German Offenlegungsschrift 2,939,269 also describes a process, in which an N-acyl-L-PTC (especially N-acetyl- L-PTC) is cleaved more rapidly than the corresponding Dderivative by means of microbial acylases which are used in the form of complete cells or of cell extracts and Soriginate from specially cultured strains of the genus Pseudomonas, Streptomyces or Aspergillus. The PTC isolated after working-up has a maximum specific rotation value of only Ea] 2 2 of 230 (c 1, 1 N HCL), which
D
corresponds to an optical purity of only about German Patent 3,048,612 has disclosed that penicillin-Gacylase, especially that from E. coli ATCC 11105, both i I i.b 2 in the free form and in the immobilized form, cleaves the Naracetyl derivatives of racemic phosphinothricin in a comparatively high yield.
Surprisingly, it has now been found that the process can be substantially improved with the aid of immobilized E.
coli cells, with respect to longer service lives and lower activity Losses.
10 The invention thus relates to a process for the enzymatic a 0 resolution of D,L-2-amino-4-methylphosphinobutyric acid, which comprises incubating N-phenacetyl derivatives thereof of the formula I o Q 0 15 II (1) P-C -CH 2-CH-NH-CO-CH -C 6 H 5 OH COOH So in an aqueous or aqueous-organic medium with E. coli ATCC 11105 cells immobilized on/in chitosan.
The invention is described in detail below, especially o its preferred embodiments. The invention is also defined in the claims.
1, 0 25 The E. coli ATCC 11105 cells are cultured in conventional S nutrient media known per' se to a person skilled in the art. For immobilization on chitosan, they are separated from the nutrient medium and fixed on chitosan by known methods, preferably by the process of German Patents 2,835,875, 3,005,632 or 3,003,633. The incubation of the substrate with the E. coli cells immobilized on chitosan can be carried out in a discontinuous or continuous column process. To render the process as economical as possible, it is preferably carried out continuously, i.e. the substrate solution is passed continuously over the fixed enzyme as the stationary phase, advantageously in a column, until the deacylation of N-phenacetyl-Lphosphinothricin is complete.
3 I The aqueous substrate solution contains the racemic phosphinothricin derivative in concentrations from about 0.1 to 30%, preferably 7 to 15%. The reaction temperature is between 20 and 45 0 C, preferably between 30 and 40°C. Adequate reactivity of the cells is obtained at a pH from 3 to 9, preferably at 6 to 8.5. The addition of organic solvents such as, for example, butyl acetate, tert.-butyl methyl ether or methyl isobutyl ketone, to the aqueous reaction solution up to saturation or washing of the immobilized enzyme with these solvents at regular intervals has an advantageous effect on the service lives thereof.
The course and the end of the reaction can be monitored by means of polarimetric methods or quantitative analysis, known from the literature, of the resulting free amino acids by reaction with ninhydrin and photometric determination of the content. Preferably, however, the liberation of phenylacetic acid is monitored by means of HPLC.
The L-PTC obtained in a high yield has a rotation value of E]22 +28.50 (c 1 in 1 N HCl), which corresponds to an optical purity of at least Surprisingly, it has been found that the economics of the biological racemate resolution by the process according to the invention, using E. coli ATCC 11105 cells can be substantially improved, in spite of the Liberation of phenylacetic acid in the course of the reaction, because of a significantly Lower activity loss and longer service Lives of the biocatalyst as compared with immobilized Spenicillin acylases.
The Examples given below serve to explain the invention in more detail.
Examples Penicillin G acylase is fixed according to German Offenlegungsschrift 2,732,301, Example 1 or 2, (biocatalyst 1) i i ;I; 4 or according to German Offentegungsschrift 3,344,912, Example 7 (biocatalyst E. coli ATCC 11105 is immobilized according to German Patent 3,005,632, Example 1, (biocatalyst Siocatatysts 1 and 2 have an activity of about 170 units/g of carrier (moist) x minute, and biocatalyst 3 has an activity of 25 units/mL of carrier x minute, each with respect to the hydrolysis of peniciLLin- G potassium salt aqueous solution) at 37 0
C.
Example 1 A 10% solution of the di-sodium or di-ammonium salt of phenacetylphosphinothricin is warmed to a temperature of 0 C at a pH of 7.7 and then pumped at a flow rate of more than 20 I/h through a glass column packed with 10 g of biocatalyst 1 or 2. The pH is readjusted to 7.7 with 0.1 normal sodium hydroxide solution or 0.1 normal ammonia solution. The substrate solution is fed, and the product stream is taken off, at 35 mL per hour (depending on the desired conversion).
The activity of the biocatalyst with respect to the hydrolysis of a 1% aqueous penicillin G potassium salt solution at a temperature of 37 0 C is determined directly or after regeneration by washing with butyl acetate solution.
Example 2 Analogously to Example 1, using 30 ml of fixed E. coli cells (biocatalyst the enzymatic hydrolysis of the 30 10% phenacetylphosphinothricin solution is carried out in a fluidized bed at pH 8.1. The enzyme activity with respect to the resolution of penicillin G potassium salt was determined according to Example 1.
Example 3 480 ml of 10% phenacetylphosphinothricin solution at pH 7.7 are warmed to a temperature of 35 0 C in a 1 liter stirred reactor with pH control. The reaction is started by adding 10 g of moist biocatalyst 1, and the p11 is readjusted by addition of diLute ammonia solution. After 24 hours, the reaction solution is separated from the blocatalyst and the reaction is started by addition of new S substrate sotution.
The resulting ExarnpLes f01l~ows.
ExampLe carrier are Listed in the Table which React ion days t im e Activity Loss S S
S'S
S'
'15 o 5.5 £55 £5 £5 o ~20 00 S 545 1 1 7 16 2 7 17 1 18 29 1 30 2 3 10 0 3 23 3 3 1 7 16 ExampLe 4 Process anaLysis, determination of conversion: HPLC Column: RP 8 Flow: 2 nt/minute Pressure: 160 180 bar Solvent: 50/50 water/methanoL (volume/volume) .PH 2.1 Detection of phenyLacetic acid: UV 206 nm
Claims (5)
1. A process for the enzymatic resolution of D,L-2-amino-4- methytphosphinobutyric acid, which comprises fLN-phenacetyL derivatives thereof of the formuLa I 01 (I) 513 I- i1 2 -cii 2 -li-Nli)-CO-C1i 2 -C 6 1 0H1 COOl! in an aqueous or aqueous-organic medium with E. coli ATCC 11105 cells immobilized on/in chitosan.
2. The process as claimed in claim 1, wherein the aqueous medium is saturated with butyL acetate, tert.-butyL methyl ether or methyt isobutyL ketone.
3. The process As claimed in claim 1 or 2, wherein the incuba- tion is carried out at 20 to 45 0 C.
4. The process as claimed in claim 3, wherein the incubation is carried out at 30 to 40 0 C. The process as claimed in one or more of claims 1 to 4, wherein the incubation is carried out at a pil from 3 to 9.
6. The process as claimed in cLaim 5, wherein the incubation is carried out at a pH from 6 to DATED) this 22nd cIny of July 1988. HOECHST AKTIENGESELLSCHIAFT EDWD. WATERS SONS PATENT ATTORNEYS QUEEN STREET MELBOURNE. VIC. 3000.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3724722 | 1987-07-25 | ||
| DE19873724722 DE3724722A1 (en) | 1987-07-25 | 1987-07-25 | IMPROVED METHOD FOR THE ENZYMATIC PRODUCTION OF L-2-AMINO-4-METHYLPHOSPHINOBUTTERIC ACID |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1973388A AU1973388A (en) | 1989-04-20 |
| AU606185B2 true AU606185B2 (en) | 1991-01-31 |
Family
ID=6332382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU19733/88A Ceased AU606185B2 (en) | 1987-07-25 | 1988-07-22 | Improved process for the enzymatic preparation of l-2-amino-4-methylphosphinobutyric acid |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0301391B1 (en) |
| JP (1) | JPS6451099A (en) |
| KR (1) | KR890002411A (en) |
| AT (1) | ATE85814T1 (en) |
| AU (1) | AU606185B2 (en) |
| CA (1) | CA1323593C (en) |
| DD (1) | DD272476A5 (en) |
| DE (2) | DE3724722A1 (en) |
| DK (1) | DK412088A (en) |
| ES (1) | ES2039515T3 (en) |
| GR (1) | GR3007701T3 (en) |
| HU (1) | HU202589B (en) |
| IL (1) | IL87218A (en) |
| ZA (1) | ZA885295B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3903446A1 (en) * | 1989-02-06 | 1990-10-18 | Hoechst Ag | METHOD FOR ENZYMATICALLY SEPARATING 2-AMINO-4-METHYLPHOSPHINOBUTTERIC ACID DERIVATIVES |
| DE59010545D1 (en) * | 1989-02-06 | 1996-11-28 | Hoechst Schering Agrevo Gmbh | Phosphine ester-containing N-acyl-2-amino acid amides, process for their preparation and N-acyl-2-amino acid nitriles as precursors |
| IL101539A (en) | 1991-04-16 | 1998-09-24 | Monsanto Europe Sa | Non-hygroscopic mono-ammonium salts of n-phosphonomethyl glycine derivatives their preparation and pesticidal compositons containing them |
| US20040053912A1 (en) * | 2000-08-28 | 2004-03-18 | Van Der Does Thomas | Process for the preparation of a beta -lactam nucleus and the application thereof |
| PT1481068E (en) * | 2002-02-26 | 2011-05-09 | Syngenta Ltd | A method of selectively producing male or female sterile plants |
| CN112940031B (en) * | 2021-02-01 | 2022-08-02 | 河北威远生物化工有限公司 | N-naphthyl-acetyl-glufosinate-ammonium, synthesis method thereof and synthesis method for synthesizing L-glufosinate-ammonium by using N-naphthyl-acetyl-glufosinate-ammonium |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4911790A (en) * | 1989-02-06 | 1990-08-09 | Bayer Cropscience Ag | Process for the enzymatic resolution of 2-amino-4-methyl- phosphinobutyric acid derivatives |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1369462A (en) * | 1971-11-23 | 1974-10-09 | Beecham Group Ltd | Enzymic resolution of racemic n-acyl-dl-amino acids |
| JPS5547630A (en) * | 1978-10-02 | 1980-04-04 | Meiji Seika Kaisha Ltd | Optical resolution of phosphorus-containing amino acid |
| DE3005632C2 (en) * | 1980-02-15 | 1985-06-05 | Joachim Prof. Dr. Klein | Process for the production of biocatalysts with high mechanical strength and high load of enzymatically active substance |
| DE3048612C2 (en) * | 1980-12-23 | 1982-12-02 | Hoechst Ag, 6000 Frankfurt | "Process for the enzymatic separation of L-2-Ami no-4-methylphosphinobutyric acid" |
-
1987
- 1987-07-25 DE DE19873724722 patent/DE3724722A1/en not_active Withdrawn
-
1988
- 1988-07-20 ES ES198888111636T patent/ES2039515T3/en not_active Expired - Lifetime
- 1988-07-20 EP EP88111636A patent/EP0301391B1/en not_active Expired - Lifetime
- 1988-07-20 AT AT88111636T patent/ATE85814T1/en not_active IP Right Cessation
- 1988-07-20 DE DE8888111636T patent/DE3878499D1/en not_active Expired - Fee Related
- 1988-07-21 HU HU883800A patent/HU202589B/en not_active IP Right Cessation
- 1988-07-21 ZA ZA885295A patent/ZA885295B/en unknown
- 1988-07-22 DK DK412088A patent/DK412088A/en not_active Application Discontinuation
- 1988-07-22 AU AU19733/88A patent/AU606185B2/en not_active Ceased
- 1988-07-22 JP JP63181946A patent/JPS6451099A/en active Pending
- 1988-07-22 DD DD88318210A patent/DD272476A5/en unknown
- 1988-07-23 KR KR1019880009265A patent/KR890002411A/en not_active Application Discontinuation
- 1988-07-25 CA CA000572951A patent/CA1323593C/en not_active Expired - Fee Related
- 1988-07-26 IL IL87218A patent/IL87218A/en not_active IP Right Cessation
-
1993
- 1993-04-27 GR GR930400606T patent/GR3007701T3/el unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4911790A (en) * | 1989-02-06 | 1990-08-09 | Bayer Cropscience Ag | Process for the enzymatic resolution of 2-amino-4-methyl- phosphinobutyric acid derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| KR890002411A (en) | 1989-04-10 |
| ZA885295B (en) | 1989-03-29 |
| HUT50214A (en) | 1989-12-28 |
| ATE85814T1 (en) | 1993-03-15 |
| ES2039515T3 (en) | 1993-10-01 |
| AU1973388A (en) | 1989-04-20 |
| DK412088A (en) | 1989-01-26 |
| GR3007701T3 (en) | 1993-08-31 |
| CA1323593C (en) | 1993-10-26 |
| IL87218A (en) | 1992-01-15 |
| DD272476A5 (en) | 1989-10-11 |
| DE3724722A1 (en) | 1989-02-16 |
| HU202589B (en) | 1991-03-28 |
| DE3878499D1 (en) | 1993-03-25 |
| JPS6451099A (en) | 1989-02-27 |
| EP0301391A1 (en) | 1989-02-01 |
| DK412088D0 (en) | 1988-07-22 |
| IL87218A0 (en) | 1988-12-30 |
| EP0301391B1 (en) | 1993-02-17 |
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