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WO1998030712A1 - Procede pour produire de l'acide aspartique cristallin - Google Patents

Procede pour produire de l'acide aspartique cristallin Download PDF

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Publication number
WO1998030712A1
WO1998030712A1 PCT/US1998/000290 US9800290W WO9830712A1 WO 1998030712 A1 WO1998030712 A1 WO 1998030712A1 US 9800290 W US9800290 W US 9800290W WO 9830712 A1 WO9830712 A1 WO 9830712A1
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WO
WIPO (PCT)
Prior art keywords
fumarate
cation exchanger
ammonium
solution
acid
Prior art date
Application number
PCT/US1998/000290
Other languages
English (en)
Inventor
Aharon Meir Eyal
Asher Vitner
Pierre Cami
Robert Jansen
Bruno Jarry
Didier Lecomte
Jean Scott
Thomas Chattaway
Frank Van Lancker
Original Assignee
Amylum Belgium N.V.
A.E. Staley Manufacturing Co.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Amylum Belgium N.V., A.E. Staley Manufacturing Co. filed Critical Amylum Belgium N.V.
Priority to AU58177/98A priority Critical patent/AU5817798A/en
Priority to US09/331,899 priority patent/US6071728A/en
Priority to EP98901724A priority patent/EP0966539A1/fr
Priority to JP53107498A priority patent/JP2001508300A/ja
Publication of WO1998030712A1 publication Critical patent/WO1998030712A1/fr

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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
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
    • C12P7/44—Polycarboxylic acids
    • C12P7/46—Dicarboxylic acids having four or less carbon atoms, e.g. fumaric acid, maleic acid
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
    • C08G69/08—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
    • C08G69/10—Alpha-amino-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
    • C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
    • C08G73/10—Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors
    • C08G73/1092—Polysuccinimides
    • 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
    • C12P13/20—Aspartic acid; Asparagine

Definitions

  • the present invention relates to a process for the production of crystalline aspartic acid.
  • Aspartic acid is an acidic amino acid with a molecular formula of HOOCCH 2 CH(NH 3 )COO. It is used in products such as the aspartame sweetener and for formation of the biodegradable polymer polyaspartic acid (PAA).
  • PAA biodegradable polymer polyaspartic acid
  • the biodegradability of PAA is very attractive, and the potential market is large. It strongly depends, however, on the availability of a low cost aspartic acid and a non-contaminating process for the preparation of aspartic acid.
  • Aspartic acid is usually produced by enzymatic conversion of diammonium fumarate, as disclosed, e.g., in US Patent 3,198,712, corresponding to British Patent 1,004,218, in which there is described and claimed a process for producing L-aspartic acid which comprises mixing Pseudomonas trifolii with an aqueous solution containing a fumaric compound selected from the group consisting of fumaric acid and fumarate and an ammonia compound selected from the group consisting of ammonia and ammonium salt, maintaining the resulting mixture at approximately neutral condition whereby L-aspartic acid forms, and recovering L-aspartic acid from said admixture.
  • the diammonium fumarate is usually a product of reacting ammonia and fumaric acid.
  • the latter is a product of converting maleic acid, which, in turn, is a petrochemical product.
  • US patent 3,391,059 describes a process wherein microorganisms capable of converting ammonium maleate directly into aspartic acid (or its salt), are isolated.
  • US patent 4,013,508 describes a process utilizing two different microorganisms. One converts hydrocarbons to fumaric acid, which is then converted by the other to aspartic acid.
  • the ammonium aspartate formed contains various impurities that could result from the enzyme, the nutrients used, products of said reactions, etc.
  • a mineral acid e.g. sulfu ⁇ c acid
  • the aspartate ion is converted to aspartic acid in zwitterionic form, which precipitates out of the solution.
  • This solution contains ammonium sulfate as the main component. The presence of the sulfate salt decreases the purity of the precipitating product due to coprecipitation of contaminants, which coprecipitation is induced by the high ionic strength.
  • Adding fumaric acid to the solution of ammonium aspartate instead of maleic acid avoids the costs and contamination related to converting maleate into fumarate in a solution, which is sent to the conversion of fumarate to aspartate. However, it does not solve all other difficulties related to product purity, losses, and to the slowing down of the bioconversion by the recycled aspartic acid.
  • Fumaric acid was produced in the past by fermentation.
  • a calcium base probably calcium carbonate, was used as a neutralizing agent in the fermentation, which resulted in calcium fumarate.
  • the fumaric acid was recovered from said salt by acidulation with sulfuric acid to form gypsum and fumaric acid.
  • This method suffered from many difficulties. Some of them resulted from the fact that the neutralizing agent, the fermentation product, calcium fumarate, the final product, fumaric acid and the by-product, gypsum, are all of low water solubility, which interferes in separation between reagents, product and by-product and between those and the biomass.
  • Another problem results from the consumption of lime and sulfuric acid and the formation of gypsum to be disposed of.
  • Fumaric acid represents, according to prior art, only about 80% of the acids formed in the fermentation. Typically malic acid, succinic acid and alpha ketoglutaric acid as well as glycerol are also formed in the fermentation.
  • the liquor formed in the fermentation contains non- utilized carbohydrates, mineral anions and cations resulting from the added nutrients, amino acids, proteins, biomass, etc.
  • a process for the production of aspartic acid comprising the steps of: (a) forming an aqueous solution containing diammonium fumarate, using per mole of diammonium fumarate about two moles of an ammonia source, a part of which is recycled from a step of the present process; (b) adjusting the composition of an aqueous solution containing diammonium fumarate obtained through a step of the present process to form a solution having a concentration of about 0.5M to about 2M ammonium fumarate and having a pH of about between 7 and 9; (c) enzymatically converting diammonium fumarate in said adjusted aqueous solution into monoammonium aspartate; (d) acidulating a solution containing said monoammonium aspartate by contacting with a cation exchanger which is at least partially in its acid form, at an elevated temperature of at least 50°C, whereby ammonium ions are transferred from said solution to said
  • ammonia source is selected from a group consisting of ammonia, ammonium carbonate and ammonium bicarbonate.
  • aqueous solution containing diammonium fumarate is formed by fermentation and a raw material for said formation in step (a) is a carbohydrate which is used as a raw material for producing said diammonium fumarate.
  • a carbohydrate-containing medium is fermented by a fumaric acid-producing microorganism.
  • Said fermentation of carbohydrate typically uses microorganisms belonging to the order Mucorales, especially Rhizopus arrhizus, Rhizopus oryzac, Rhizopus nigricans or other related genera. Other microorganisms like Candida may be used alternately.
  • the fermentation medium can contain, in addition to the carbohydrate, nutrients such as nitrogen sources and minerals.
  • Suitable nitrogen sources include such organic and inorganic sources as urea, ammonium chloride, ammonium sulfate, ammonium acetate, ammonium nitrate, ammonium biphosphate, asparagin and protein hydrolysates. Of the foregoing, urea and ammonium sulfate are preferred.
  • the inorganic salts added to the culture media could include sources of phosphate, sulfur, iron magnesium and zinc. Suitable ?
  • sources of phosphate include monobasic or dibasic sodium phosphate, monobasic or dibasic potassium phosphate, ammonium biphosphate, or mixtures thereof.
  • Suitable inorganic salts employed in the fermentation include zinc sulfate, iron salts such as ferric tartrate or ferric chloride, and magnesium sulfate. Corn steep liquor or biotin may be added for vitamin supply.
  • the fermentation is conducted at a temperature of about 25°C to about 35°C, preferably at about 33°C to about 35°C.
  • a process as herein before defined comprising the steps of: (a) fermenting a carbohydrate-containing medium by means of a fumaric acid- producing microorganism, whereby a fumarate containing fermentation liquor is formed; (b) adjusting the composition of an aqueous solution containing diammonium fumarate obtained through a step of the present process to form a solution having a concentration of about 0.5M to about 2M ammonium fumarate and having a pH of about between 7 and 9; (c) enzymatically converting diammonium fumarate into monoammonium aspartate; (d) acidulating a solution containing said monoammonium aspartate by contacting with a cation exchanger which is at least partially in its acid form, at an elevated temperature of at least 50°C, whereby ammonium anions are transferred from said solution to said cation exchanger and protons are transferred from said cation exchanger to said solution forming aspart
  • Fungi can grow satisfactorily in acidic conditions.
  • the build-up of fumaric acid in the fermentation medium has a negative effect on the fermentation, the latter is typically conducted at a slightly acidic pH, from about 4 to 7.
  • a base is directly added as a neutralizing agent and a fumarate salt is formed.
  • the neutral salt of fumaric acid is formed rather than the acidic salt.
  • Said neutralizing agent can be selected from a group consisting of ammonia and hydroxides, carbonates or bicarbonates of ammonium, alkali and alkaline earth metals. Most preferably calcium carbonate is used as a neutralizing agent and calcium fumarate is formed.
  • the carbohydrate is selected from the group consisting of dextrose, preferably produced from cereal starch, including low-grade wheat starch fractions and molasses.
  • the fumaric acid is continuously removed from the fermentation medium, e.g. by binding to a water immiscible liquid or solid basic extractant or adsorbent.
  • a basic extractant e.g. of the type containing a long chain amine, or a basic resin such as the anion exchangers that carry non-quaternary amine functions or pyridine based resins.
  • the anion exchanger is a relatively strong one, most preferably of a pKa higher than 5.
  • the fumaric acid can be recovered from said extractant or adsorbent by contacting with a basic solution which consumes a base and forms the fumarate salt.
  • a base will further be referred to as indirect neutralization, it being realized that a base can be used directly or indirectly as a neutralizing agent in said fermentation.
  • the base for that purpose is preferably selected from the group consisting of ammonia and hydroxides, carbonates and bicarbonates of ammonium, alkali and alkaline earth metals. Most preferably this base is ammonia.
  • Ammonium fumarate is enzymatically converted to ammonium aspartate. Usually the conversion is conducted in a slightly basic medium so that diammonium fumarate is the substrate. Ammonium fumarate formed in fermentation could be fed to said enzymatic conversion. (As used herein, if not defined specifically, the term ammonium fumarate is intended to denote monoammonium fumarate, diammonium fumarate, or a combination thereof) In those cases where the fermentation results in another fumarate salt, as in the case of the preferred embodiment where calcium carbonate is the neutralizing agent and calcium fumarate is the product, this salt is converted to ammonium fumarate. This is preferably effected by a direct or an indirect reaction with ammonia, ammonium carbonate or ammonium bicarbonate.
  • Precipitated calcium fumarate formed in the fermentation is separated from the fermentation liquor, washed, suspended in water or in an aqueous solution from a previous step and dissolved at an elevated temperature.
  • the calcium fumarate solution can be purified, if needed, by methods such as / /
  • the membrane filtration, ion-exchange, active carbon treatment, solvent extraction, etc. is preferably recrystallized. After recrystallization it is reacted with ammonia and CO 2 or with ammonium carbonate or bicarbonate or mixtures thereof.
  • the pH in the reaction medium is first adjusted to between about 10 and 11. High temperatures and high CO 2 pressures are not required.
  • calcium fumarate is converted to ammonium fumarate.
  • the amount of water in the reaction is adjusted so that the ammonium fumarate formed will be quite concentrated, preferably greater than 10% and even more preferred higher than 13%.
  • Calcium carbonate is formed as a by-product, separated from the ammonium fumarate solution and reused as a neutralizing agent, in carbohydrates fermentation to fumaric acid.
  • the calcium carbonate is calcined prior to the recycle to fermentation, whereby biomass left in it is removed.
  • the calcined calcium base is quenched in water and kept suspended in the water until reused. This suspension in water helps in removing ashes left from biomass burning and other ashes left from the previous fermentation step.
  • ammonium fumarate directly formed in the fermentation or indirectly through conversion of another fumarate salt formed in the fermentation is purified prior to the enzymatic conversion to ammonium aspartate. Purification can be conducted in known methods such as recrystallization, membrane filtration, ion-exchange, active carbon treatment, solvent extraction, etc.
  • ammonium fumarate is purified through a reaction with a calcium compound whereby calcium fumarate forms. Said calcium fumarate is crystallized and, if desired, recrystallized and /P-
  • the calcium compound is a calcium base selected from the group consisting of calcium oxide, hydroxide, carbonate and bicarbonate.
  • said calcium base is obtained from calcium carbonate recycled from conversion of calcium fumarate to ammonium fumarate.
  • ammonium fumarate is converted to ammonium aspartate in an enzymatically catalyzed reaction.
  • ammonium aspartate is monoammonium aspartate, but a small fraction could be in diammonium aspartate form.
  • ammonium aspartate as used herein is intended to denote both monoammonium aspartate and its mixtures with diammonium aspartate, unless otherwise indicated.
  • the enzymatic reaction is catalyzed by the enzyme aspartase.
  • This enzyme can be produced from many microorganism, including E.coli, Brevibacterium sp, Pseudomonas sp. cultivated in a suitable medium.
  • the ammonium aspartate formation can be obtained by contacting the ammonium fumarate solution directly with the bacterial culture or with permeabilized cells, crude cell extracts, or purified aspartase.
  • bacterial culture is used directly, the method described in French Patent Publication No. 2,197,979 (1972) can be employed.
  • Cell culture, • cells, cell extracts or enzyme itself can be used directly or as immobilized preparations.
  • Examples of immobilized preparations are obtained by immobilizing the cells, cell extracts or enzyme on supports, carriers or bases such as polyacrylamide gels, sulfur-containing polysaccharide (e.g. carrageenan, furcellaran, etc.), gel, collagen gel, alginic acid gel, polyvinyl alcohol gel, agar gel, resins and the like.
  • the ammonium fumarate concentration in the feed to the conversion is typically from about 0.5M to about 2M.
  • the amount of the divalent ion can be about 0.1 to 10mM.
  • the reaction is conducted at temperatures of from about 20°C to 60°C, and the pH is preferably between 7 to 9.
  • the yield of conversion is typically 90% to 100%.
  • the pKa's of aspartic acid are 1.88, 3.65 and 9.60, and its isoelectric point (pi) is 2.77.
  • the aspartate-containing solution obtained in the conversion is about neutral or even slightiy basic. At these conditions both carboxylic functions are negatively charged. One of them is balanced by the positively-charged ammonium group and the other by a cation, ammonium in most cases.
  • This solution is acidulated through contact with a cation exchanger, the functional groups of which are at least partially in proton form. Due to the contact, cation exchange is effected, cations from the solution are adsorbed and protons are transferred from the cation exchanger to the solution, lowering its pH. Those protons react with at least one of the carboxylic groups on the aspartate (the one related to the pKa of 3.65) to form the zwitterion.
  • the solubility of the aspartic acid in the zwitterion form is low and its crystallization in the cation exchanger could damage the resin and interfere with its operation. Temperature elevation does not always solve the problem. Firstly, it is limited by the thermal stability of the resin and secondly the H
  • the acidulated solution is separated from the ammonium ion-carrying cation exchanger and the latter is sent to regeneration in contact with an acidic solution.
  • the separation is preferably effected without cooling the solution much below the temperature of the acidulation step.
  • Aspartic acid is separated from the aspartic acid-containing aqueous solution formed on contact with the cation exchanger by known methods. Preferably this separation is effected by crystallization, e.g. by cooling and/or by water evaporation, or solvent addition.
  • the present process provides a possibility of .high yield recovery of aspartic acid from the mother liquor by an additional step.
  • aspartic acid In contacting this mother liquor with a strong acid cation exchanger, aspartic acid obtains an additional proton from the cation exchanger and transforms into the cationic form. As such it is efficiently bound from the mother liquor.
  • a strong acid cation exchanger in its acid form is contacted with the mother liquor of aspartic acid crystallization.
  • the aspartic acid contained in that mother liquor is adsorbed.
  • the aspartic acid carrying cation exchanger resulting from that step is contacted with a solution of the aspartate salt obtained in the conversion step.
  • Said acidic solution is preferably containing a solute selected from the group consisting of fumaric acid, monoammonium fumarate and mixtures thereof. More preferably, said solution is obtained in another step of the present process.
  • the aqueous solution containing the aspartate salt obtained in the bio-conversion reaction is first contacted with the weak acid cation exchanger, and the resulting solution is contacted with the strong acid cation exchanger resulting from the contact with the mother liquor.
  • the aqueous solution obtained in that contact is sent to the aspartic acid crystallization. Regeneration of the resins is done in the following sequence: the regeneration acidic solution is first l b
  • the free mother liquor obtained contains most of the impurities resulting from the various sources. As it is essentially aspartic acid free, there is no need to recycle it to the enzymatic conversion (directly or indirectly). Therefore, recycle of impurities and their build-up in the system are avoided.
  • the ammonium ion-carrying cation exchanger, formed in the ammonium aspartate acidulation step, is regenerated to its at least partial acid form for reuse, in a method wherein an ammonia source is formed.
  • That ammonia source is preferably selected from the group consisting of ammonia, ammonium carbonate and ammonium bicarbonate.
  • Regeneration methods forming acidic or neutral ammonium salts of a mineral acid are preferably avoided.
  • treatment with a strong mineral acid, such as sulfuric acid forms neutral ammonium salts of said acid, e.g. ammonium sulfate which is not desired in the process apart from a small amount in fermentation and should be avoided or limited.
  • ammonium ion-carrying cation exchanger is treated with CO 2 as a reagent, preferably under pressure.
  • a solution of ammonium carbonate or bicarbonate or mixtures thereof is formed as an ammonia source for reuse.
  • Such a solution could be reused as such or after treatments such as concentration or distillation..
  • Said distillation forms ammonia or ammonia mixtures with CO 2 and optionally also water vapors. Those could then be used as ammonia sources. n
  • the cation exchanger used for acidulating ammonium aspartate is preferably of a weak acid or a medium acid properties. Strong acid cation exchangers, e.g. of the sulfonate type, are preferably avoided as their conversion back to the partially acidic form requires relatively strong acid. Yet, according to one of the preferred embodiments of this invention, fumaric acid is formed. This fumaric acid can be used for that purpose as well as for the regeneration of a strong acid cation used for recovery of aspartic acid from crystallization mother liquor.
  • CO 2 as a reagent for regenerating the cation exchanger
  • a solution containing monoammonium fumarate, fumaric acid or mixtures thereof whereby protons are transferred from said solution to the cation exchanger and ammonium ions are transferred from said cation exchanger to said solution to form diammonium fumarate therein.
  • Monoammonium fumarate, fumaric acid or a mixture thereof for regeneration of said ammonium-carrying cation exchanger are obtained by decomposition of diammonium fumarate in a method which also forms an ammonia base.
  • diammonium fumarate resulting from fermentation is decomposed.
  • diammonium fumarate formed in said regeneration step is decomposed.
  • diammonium fumarate resulting from fermentation is fed after adjustment to the enzymatic «
  • diammonium fumarate formed in said regeneration step is fed after adjustment to the enzymatic conversion.
  • Said adjustment could consist of steps such as adjusting the concentration and pH and adding components, as needed, e.g. a salt of a bivalent metal, in the enzymatic conversion step.
  • Such adjustment could also consist of a purification step by known methods such as recrystallization, membrane filtration, membrane dialysis or electrodialysis, ion exchange, active carbon treatment, solvent extraction, etc.
  • said decomposition to monoammonium fumarate and an ammonium base serves as a purification means.
  • Monoammonium fumarate is crystallized out of the solution in a rather pure form. It can be further purified, if needed, e.g. by recrystallization.
  • this purified monoammonium fumarate is converted to diammonium fumarate by contacting with ammonium ion-carrying cation exchanger, e.g. that formed on acidulation of ammonium aspartate, preferably after washing, the diammonium fumarate solution formed is fed, after adjustment to said enzymatic conversion.
  • ammonium fumarate is purified through a reaction with a calcium compound, whereby calcium fumarate forms. Said calcium fumarate is crystallized and, if desired, recrystallized and purified by other known means. Then said calcium fumarate is converted back to ammonium fumarate by means described above.
  • the calcium compound is a calcium base selected from a group consisting of calcium oxide, hydroxide, carbonate and bicarbonate. In a most preferred embodiment said calcium base is obtained from calcium carbonate which is recycled from conversion of calcium fumarate to ammonium fumarate.
  • Said decomposition of diammonium fumarate is preferably effected by at least one method selected from a group consisting of: (i) electrodialytic water splitting;
  • Electrodialytic water splitting is effected by a device containing charged membranes including bipolar membranes and uses electric energy as a driving force. It could split diammonium fumarate to ammonia and fumaric acid and/or monoammonium fumarate.
  • the ammonia is obtained as relatively concentrated solution and could be used as such or after distillation as an ammonia source. In most cases monoammonium fumarate will be preferred as the other product due to its higher solubility, avoiding the risk of crystallines that could interfere with the operation of the bipolar membrane.
  • Such water immiscible base is selected from a group consisting 1 0
  • Suitable extractants contain high molecular weight amines with a total number of carbon atoms of at least 18. Preferably those are aliphatic secondary or tertiary amines.
  • the amine is dissolved in a solvent or a mixture of solvents. Preferably such solvent contains an alkanol acting as an extraction enhancer.
  • Basic solid adsorbents are anion exchangers carrying non-quaternary amine groups or pyridine- based resins.
  • the bound fumaric acid can be stripped by washing with water at an elevated temperature, preferably close to or above 100°C.
  • the fumaric acid-loaded base is stripped with an aqueous solution of diammonium fumarate. Fumaric acid transfers to said solution forming monoammonium fumarate therein.
  • monoammonium fumarate is crystallized out of the solution formed and the remaining solution is reused to form a diammonium fumarate containing stripping solution.
  • the contact under CO 2 and stripping with water and/or an aqueous solution of diammonium fumarate are conducted in a counter current mode.
  • a part of the bound fumaric acid is stripped by water and then another part of it is stripped with an aqueous solution of diammonium fumarate.
  • an aqueous solution of diammonium fumarate is acidulated by contacting with a cation exchanger, which is at least partially in its acid form.
  • Ammonium ions transfer from said aqueous solution to the cation exchanger and protons transfer from said cation exchanger to the solution forming monoammonium fumarate therein.
  • the solution is separated from the ammonium ion-carrying cation exchanger, which is regenerated by 31
  • transformation back to the at least partially acid form preferably after first washing with water or an aqueous solution.
  • this regeneration is effected by water under CO 2 pressure.
  • An aqueous solution containing ammonium bicarbonate, carbonate or a mixture thereof, is formed and is used as an ammonia source.
  • said separated aqueous solution is treated for the separation of monoammonium fumarate therefrom, preferably by crystallization.
  • the remaining solution is preferably used to reconstitute an aqueous solution of diammonium fumarate for further decomposition to an ammonia source and monoammonium fumarate or fumaric acid.
  • diammonium fumarate is thermally decomposed into ammonia and monoammonium fumarate. Heating of solid diammonium fumarate or a solution thereof to a temperature of above 100°C and more preferably to above 150°C results in removal of ammonia to the vapor phase and in the conversion of at least part of the diammonium fumarate to monoammonium fumarate. Said ammonia is recovered and used as an ammonia source. In a preferred embodiment said monoammonium fumarate is separated from the decomposition product, preferable by crystallization. The rest of the decomposition product is preferably used to reconstitute a diammonium fumarate feed for further decomposition to an ammonia source and monoammonium fumarate or fumaric acid.
  • the cation exchanger used for acidulation of diammonium fumarate is selected from a group consisting of weak or medium acid strength cation exchangers. It could be the same cation exchanger used for the acidulation of ammonium aspartate or of similar acidity. Preferably it is somewhat less acidic.
  • an aqueous solution containing monoammonium fumarate formed by decomposition of diammonium fumarate is contacted with a suitable water immiscible base.
  • a suitable water immiscible base is selected from a group consisting of extractants and basic solid adsorbents.
  • Suitable extractant contain high molecular weight amines with a total number of carbon atoms of at least 18. Preferably those are aliphatic secondary or primary amines. The amine is dissolved in a solvent or a mixture of solvents.
  • such solvent contains an alkanol acting as an extraction enhancer.
  • Basic solid adsorbents are anion exchangers carrying non-quatenary amine groups, or pyridine- based resins.
  • the water immiscible base could be similar to that used in decomposition of diammonium fumarate under CO 2 pressure or of a similar basicity. Preferably it is somewhat weaker.
  • the bound fumaric acid can be stripped by washing with water at an elevated temperature, preferably close to or about 100°C. Alternatively, a combination of stripping with water and with a diammonium fumarate solution is effected as suggested above. In a preferred embodiment the contact with the monoammonium fumarate and stripping with water are conducted in a counter current mode.
  • electrodialytic water splitting contact with a water immiscible base under CO 2 pressure, thermal decomposition, and acidulation by contact with a cation exchanger, which is at least partially in acid form, or a combination thereof, result in decomposition of diammonium fumarate to an ammonia source, which is ammonia, ammonium carbonate, ammonium bicarbonate or mixture thereof, and in fumaric acid, monoammonium fumarate 22
  • the ammonia source is used as a neutralizing agent in the fermentation or for converting a fumarate formed in said fermentation into ammonium fumarate.
  • the monoammonium fumarate or fumaric acid is used to regenerate ammonium ion-carrying cation exchangers formed in the acidulation of ammonium aspartate or by the recovery of aspartic acid from a mother liquor formed on crystallizing aspartic acid. In those cases where monoammonium fumarate is formed, it is preferably crystallized out of solutions containing it and more preferably recrystallized as a means of purification.
  • the 1.42 Kg. wet cake was re-suspended in 1.5Kg de-ionized water at 30C and 344g of a 33% ammonia solution was added. Gaseous CO2 was then bubbled through the suspension until the pH was 8.7. After cooling the ambient temperature the suspension was filtered and the cake was washed with 1.2 Kg. water. The wash water was combined with the filtrate.
  • the composition of the combined solution was 257g (2.21 mole) fumarate (>90% conversion), 2.2g. (0.016 mole) maleate, 8.2g. (0.069 mole) succinate, 0.4g (0.003 mole) alpha ketoglutarate 0.18g (0.0045 mole) calcium and 90g (5 mole) ammonia.
  • 125g octanol were placed in a beaker and heated to 170°C.
  • 40g of an aqueous solution containg 2.5M(NH4)2Fu were added in drops to the hot octanol during 2 hours. Heating was continued for additional 45 minutes and then stopped.
  • the crystals formed were separated, washed with ethanol and dried. 0.5g of the dry crystals were dissolved in 10g water. The pH of the solution was 3.45, slightly lowever than that of NH4HFu solution of the same concentration.
  • a 10 liter sterile solution containing 1270g dextrose, 17.5g (NH 4 ) SO4, 4g MgSO 4 .7H 2 O, 3g KH 2 PO 4 , 0.5g ZnSO 4 .7H 2 O, 0.1g FeCI 3 .6H 2 O, 5g corn steep liquor and 960g of CaCO 3 in suspension is fermented at 34°C using Rhizopus arrhizus strain NRRL 1526.
  • the broth is filtered to get a cake of the mycelium and calcium fumarate which is washed with 2 liters of cold water.
  • the washed cake contains 720g of fumaric acid as its calcium salt.
  • the cake is suspended in 12 liters of boiling water with agitation for one hour and then filtered at 95°C to obtain a calcium fumarate solution.
  • Calcium fumarate is crystallized by cooling the filtrate at 10°C for 2 hours.
  • the calcium fumarate is filtered, washed in 1 liter of cold water and dried to obtain 850g of calcium fumarate, with a purity higher than 90%. 790g of this calcium fumarate is suspended in 4.5 liters of 180g ammonia water solution and CO 2 is bubbled until the pH reaches 8.5. Calcium carbonate precipitate is filtered and washed in cold water. 4.5 liters of diammonium fumarate solution containing 540g of fumaric acid is obtained.
  • the crystals are separated by filtration and dissolved in water at 75°C.
  • the solution is percolated on a 2 liter column B, containing a cation exchanger carrying ammonium ions obtained from a previous step of acidulating ammonium aspartate.
  • a 1.5 liter solution is formed, containing 180 g of fumaric acid in its diammonium fumarate form.
  • the cation exchanger is practically completely regenerated to its acid form.
  • the pH of the diammonium fumarate solution is adjusted to 8.
  • the bacterium Pseudomonas fluorescens strain ATCC 21973 it is converted, at 58°C, to monoammonium aspartate solution at a molecular yield higher than 95%.
  • the solution of the monoammonium aspartate is heated to 75°C and acidulated by percolating on column B. On cooling the effluent to 10°C, more than 85% of its aspartic acid content crystallized as pure aspartic acid.

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Abstract

Un procédé permettant de produire de l'acide aspartique comprend les étapes suivantes: (a) on forme une solution aqueuse contenant du fumarate dibasique d'ammonium en utilisant par mole de fumarate environ deux moles d'une source d'ammoniaque, dont une partie est recyclée à partir d'une étape du présent procédé; (b) on ajuste la composition d'une solution aqueuse contenant le fumarate dibasique d'ammonium obtenu par une étape du présent procédé, de façon à former une solution ayant une concentration comprise entre 0,5 et 2 M environ de fumarate d'ammonium et un pH compris entre 7 et 9 environ; (c) on convertit par une action enzymatique le fumarate dibasique d'ammonium, dans la solution aqueuse ajustée, en aspartate monobasique d'ammonium; (d) on acidifie une solution contenant l'aspartate monobasique d'ammonium en la mettant en contact avec un échangeur de cations, qui se trouve au moins partiellement sous sa forme acide, à une température élevée d'au moins 50 °C, les ions ammonium étant transférés de la solution à l'échangeur de cations et les protons étant transférés de l'échangeur de cations à la solution, ce qui forme dans celle-ci de l'acide aspartique; (e) on sépare la solution aqueuse contenant l'acide aspartique de l'échangeur de cations portant les ions ammonium; (f) on sépare l'acide aspartique de la solution aqueuse formée à l'étape (e) par des procédés connus en soi; (g) on régénère l'échangeur de cations portant les ions ammonium, de façon à obtenir un échangeur de cations qui se trouve au moins partiellement sous sa forme acide, selon un procédé qui forme une source d'ammoniaque; (h) on sépare et on réutilise l'échangeur de cations converti à l'étape (d); et (i) on sépare et on réutilise la source d'ammoniaque à l'étape (a).
PCT/US1998/000290 1997-01-09 1998-01-08 Procede pour produire de l'acide aspartique cristallin WO1998030712A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU58177/98A AU5817798A (en) 1997-01-09 1998-01-08 A process for the production of crystalline aspartic acid
US09/331,899 US6071728A (en) 1997-01-09 1998-01-08 Process for the production of crystalline aspartic acid
EP98901724A EP0966539A1 (fr) 1997-01-09 1998-01-08 Procede pour produire de l'acide aspartique cristallin
JP53107498A JP2001508300A (ja) 1997-01-09 1998-01-08 結晶性アスパラギン酸の製造方法

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IL119986 1997-01-09
IL11998697A IL119986A (en) 1997-01-09 1997-01-09 Process for the production of crystalline aspartic acid

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WO1998030712A1 true WO1998030712A1 (fr) 1998-07-16

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0974613A3 (fr) * 1998-07-23 2000-06-28 Nippon Shokubai Co., Ltd. Procédé de production de polymère du type polysuccinimide et d'acide polyaspartique
EP2918574A1 (fr) 2009-12-31 2015-09-16 Groupe Novasep SAS Purification d'acide succinique à partir d'un bouillon de fermentation contenant de succinate d'ammonium
CN117285431A (zh) * 2023-09-22 2023-12-26 安徽雪郎生物科技股份有限公司 一种l-天冬氨酸结晶母液的处理方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4742610B2 (ja) * 2005-02-23 2011-08-10 三菱化学株式会社 フマル酸の製造方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0683231A1 (fr) * 1994-05-20 1995-11-22 Nippon Shokubai Co., Ltd. Procédé de production d'acide L-aspartique
EP0752476A1 (fr) * 1994-12-09 1997-01-08 Mitsubishi Chemical Corporation Procede de production d'acide l-aspartique
WO1997027312A1 (fr) * 1996-01-22 1997-07-31 Amylum N.V. Procede de preparation d'acide aspartique
WO1998003468A1 (fr) * 1996-07-18 1998-01-29 Amylum N.V. Procede de production d'acide aspartique cristallin

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0683231A1 (fr) * 1994-05-20 1995-11-22 Nippon Shokubai Co., Ltd. Procédé de production d'acide L-aspartique
EP0752476A1 (fr) * 1994-12-09 1997-01-08 Mitsubishi Chemical Corporation Procede de production d'acide l-aspartique
WO1997027312A1 (fr) * 1996-01-22 1997-07-31 Amylum N.V. Procede de preparation d'acide aspartique
WO1998003468A1 (fr) * 1996-07-18 1998-01-29 Amylum N.V. Procede de production d'acide aspartique cristallin

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0974613A3 (fr) * 1998-07-23 2000-06-28 Nippon Shokubai Co., Ltd. Procédé de production de polymère du type polysuccinimide et d'acide polyaspartique
US6300105B1 (en) 1998-07-23 2001-10-09 Nippon Shokubai Co., Ltd. Methods for producing a succinimide polymer, an aspartic acid polymer and L-aspartic acid
EP2918574A1 (fr) 2009-12-31 2015-09-16 Groupe Novasep SAS Purification d'acide succinique à partir d'un bouillon de fermentation contenant de succinate d'ammonium
US9233906B2 (en) 2009-12-31 2016-01-12 Group Novasep SAS Purification of succinic acid from the fermentation broth containing ammonium succinate
CN117285431A (zh) * 2023-09-22 2023-12-26 安徽雪郎生物科技股份有限公司 一种l-天冬氨酸结晶母液的处理方法

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AU5817798A (en) 1998-08-03
JP2001508300A (ja) 2001-06-26
IL119986A0 (en) 1997-04-15
EP0966539A1 (fr) 1999-12-29

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