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
1996-06-05
2000-01-11
Marx, Irene
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing alpha or beta amino acid or substituted amino acid...
435136, 435116, 532569, C12P 1304, C12P 1306
Patent
active
060134925
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a process for producing calcium D-pantothenate from a fermentation broth of D-pantothenic acid directly produced with a microorganism. Calcium D-pantothenate has been widely used as a vitamin in medicines, foods, feeds, etc.
BACKGROUND OF THE INVENTION
Conventional processes for producing calcium pantothenate can be classified roughly into chemical synthesis processes and direct fermentation processes. A chemical synthesis process widely used in industrial production comprises subjecting D,L-pantolactone synthesized from the starting compound isobutylaldehyde to optical resolution by a chemical or enzymatic method and condensing the resulting D-pantolactone with .beta.-alanine calcium to obtain calcium D-pantothenate. As a direct fermentation method, JP-A 6-261772 has recently disclosed a novel process for directly producing D-pantothenic acid with a microorganism from a saccharide and .beta.-alanine. In particular, it discloses a process for producing calcium D-pantothenate from a direct fermentation broth of D-pantothenic acid, which comprises subjecting the fermentation broth to desalting with ion-exchange chromatography, followed by neutralization to concentrate the D-pantothenic acid as a calcium salt, and adding methyl alcohol (methyl alcohol concentration: 83 v/v %) to precipitate crystals of calcium D-pantothenate.
Direct fermentation processes are more efficient than chemical synthesis processes because they require no optical resolution, etc. However, the fermentation broth contains insoluble materials such as microbial cells, etc., and various soluble impurities such as monosaccharides, oligosaccharides, organic acids, proteins, inorganic salts (cations, anions), etc., in addition to D-pantothenic acid. Therefore the most important problem has been how to efficiently separate and purify calcium D-pantothenate from the fermentation broth in high yield and purity. As described above, JP-A 6-261772 discloses a process for producing calcium D-pantothenate from a direct fermentation broth of D-pantothenic acid, which comprises subjecting the fermentation broth to desalting with ion-exchange chromatography, followed by neutralization to concentrate the D-pantothenic acid as a calcium salt, and adding methyl alcohol (methyl alcohol concentration: 83 v/v %) to precipitate crystals of calcium D-pantothenate. However, this process has the following drawbacks. (i) The treatment with an ion-exchange resin can not remove monosaccharides or oligosaccharides contained in the fermentation broth, and the crystallization raw solution contains them in an amount of about 10% based on pantothenic acid. These remaining monosaccharides or oligosaccharides cause coloring with heat during concentration of the ion-exchange resin treatment solution or a lowering of the crystallization yield during crystallization. (ii) In order to obtain high crystallization yield, the solution treated with ion-exchange resin must be concentrated to obtain a high concentration (about 50%) of calcium D-pantothenate before addition of methyl alcohol so that the concentration of calcium D-pantothenate in the crystallization raw solution becomes not less than 7 w/v% and the methyl alcohol concentration becomes about 90 v/v %. The calcium D-pantothenate solution in such concentration has a very high viscosity, which makes it difficult to concentrate the solution.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram of a fixed bed in which Columns A and B packed with activated carbon are connected in series. The symbols (i) to (vi) represent passages.
FIG. 2 shows break-through curves obtained when the liquid to be treated was passed through LH2C carbon column. The thin solid line A represents a break-through curve of D-pantothenic acid. The heavy solid line B represents a break-through curve of saccharides. (a) is a break-through adsorption point of D-pantothenic acid. (b) is a saturated adsorption point of D-pantothenic acid.
FIG. 3 shows elution curves obtained in the elution fr
REFERENCES:
Database WPI, Derwent Publications Ltd., abstract No. 94-221861., JP-A-06 157 439, Jun. 3 1994.
Database WPI, Derwent Publications Ltd., abstract No. 77-89596Y., SU-A-541 839, Feb. 2 1977.
Database WPI, Derwent Publications Ltd., abstract No. 74-61182V., SU-A-403 670, Mar. 27, 1974.
Database WPI, Derwent Publications Ltd., abstract No. 66-28489F., SU-A-188 397, priority date Sep. 26, 1964.
Patent Abstracts of Japan, Shingo et al., "Preparation of Vitamin P", 54101412. Aug. 10, 1979 Jan. 25, 1978, 53007769.
Patent Abstracts of Japan, Yosuke et al., "Production of Natural Vitamin K Condensate", 05155803, Jun. 22, 1993, Nov. 30, 1991, 03342164.
Matsumoto Jun-ichi
Miki Hiroshi
Nishimura Sunao
Shibutani Kosaku
Yada Hideo
Marx Irene
Takeda Chemical Industries Ltd.
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