Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing alpha or beta amino acid or substituted amino acid...
Patent
1998-10-13
1999-10-26
Lilling, Herbert J.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing alpha or beta amino acid or substituted amino acid...
562571, C12P 1320, C07C22900
Patent
active
059726628
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a process for the production of aspartic acid.
More particularly, the present invention relates to the preparation of aspartic acid via a fermentation process for the preparation of ammonium fumarate.
Aspartic acid is the 2-aminobutanedioic acid, occurring in its L-form in animals and plants. It is a reagent in the production of the artificial sweetener aspartame. L-Aspartic acid is one of the amino acids that is difficult to produce directly by fermentation. Consequently it is produced enzymatically by conversion of diammonium fumarate to ammonium aspartate which is then acidulated.
GB 1 004 218 discloses a process for the production of L-aspartic acid, comprising mixing a strain of Pseudomonas trifolii with an aqueous solution of fumaric acid or a fumarate, and ammonia or an ammonium salt, allowing the mixture to stand under neutral or mildly alkaline conditions to allow L-aspartic acid to accumulate therein, and recovering. the L-aspartic acid from the mixture. Preferably diammonium fumarate serves as both the fumarate and the ammonium salt.
Diammonium fumarate is obtained by neutralizing fumaric acid with ammonia. About one half of the total aspartic acid production cost is due to the fumaric acid consumed. Fumaric acid is presently produced by catalytical isomerisation of maleic anhydride or maleic acid produced mostly from benzene. In the early 1940's fumaric acid was made on a commercial scale by Pfizer by fermentation of glucose using a strain of the fungus Rhizopus. Production was stopped when the economically more attractive synthesis from maleic acid was developed.
Since then many improvements to the fermentation were made. U.S. Pat. No. 4,877,731 describes an improved fermentation process for producing carboxylic acids. The improvement comprises growing fungi of the genus Rhizopus in a culture medium under conditions of controlled oxygen availability. Goldberg and Steiglitz (Biotechnology and Bioengineering Vol. 27, 1067-1069 (1985) have found that adding surfactants or vegetable oils increased the rate of fumaric acid accumulation. Other improvements and optimizations were made by Rhodes et. al (Applied Microbiology, 7, 74-80 (1959)), Moresi et. al (Applied Microbiology and Biotechnology, 36, 35-39, 1991), Kautola and Linko (Applied Microbiology and Biotechnology, 31, 448-482 (1989)) and others.
In spite of these improvements fumaric acid is not produced presently by fermentation. This is at least partially due to the complicated and costly process for its recovery from the fermentation broth. In the fermentation, as the pH of the broth drops in consequence of production, the rate of fumaric acid production slows down and eventually ceases. CaCO.sub.3 is added as a neutralizing agent to prevent this self-inhibition. Because of its insolubility, CaCO.sub.3 offers the advantage of all-at-once addition and therefore eliminates the requirement of a control system for base addition. However, because of the low solubility of calcium fumarate at the fermentation temperature, the product precipitates out of the broth throughout the fermentation. At the end of the fermentation. the broth, containing a slurry of calcium fumarate. is heated to 160.degree. C. in a reactor and is acidified to pH 1.0 by H.sub.2 SO.sub.4. At this temperature, both calcium fumarate and fumaric acid are soluble, but calcium sulfate precipitates out of solution and is filtered off. Fumaric acid crystals are recovered by cooling the filtrate.
The overall process thus consumes CaCO.sub.3 and H.sub.2 SO.sub.4 as reagents produces gypsum as an undesired by-product, consumes energy for the reaction at high temperature and requires handling an acidic solution at very high temperatures. All these elements add to the cost of fumaric acid production through fermentation and render fumaric acid, produced by fermentation, an unfavorable reagent for aspartic acid manufacture.
Conversion of fumaric acid fermentation to aspartic acid fermentation by the combination of Rhizopus and bacteria (Proteus vulgaris)
REFERENCES:
patent: 3030276 (1962-04-01), Thompson
patent: 4877731 (1989-10-01), Ling et al.
patent: 5352825 (1994-10-01), Felman et al.
R.A. Rhodes et al., "Production of Fumaric Acid by Rhizopus arrhizus", vol. 7, pp. 74-80.
K. Hotta et al., "Conversion of Fumaric Acid Fermentation to Aspartic Acid Fermenation by the Association of Rhizopus and Bacteria", J. Ferm. Tech., vol. 51, No. 1, pp. 12-18, 1973.
I. Goldberg et al., "Improved Rate of Fumaric Acid Production by Tweens and Vegetable Oils in Rhizopus arrhizus", Biotech. & Bioeng., vol. 27, No. 7, Jul. 1985, pp. 1067-1069.
M. Moresi et al., Optimization of fumaric acid production from potato flour by Rhizpus arrhizus, Appl. Micro. Biotech. (1991), 36:335-39.
H. Kautola et al., "Fumaric acid production from xylose by immobilized Rizopus arrhizus cells", Appl. Microbiol. Biotech. (1989), 31:448-452.
I.C. Gangl et al., "Economic Comparison of Calcium Fumarate and Sodium Fumarate Production by Rhizopus arrhizus", Appl. Biochem. Biotech., vol. 24/25, 1990, pp. 663-677.
Cami Pierre
Eyal Aharon
A.E. Stanley Manufacturing Company
Amylum N.V.
Lilling Herbert J.
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