USRE45723E1 - Process for producing amino acids - Google Patents

Process for producing amino acids Download PDF

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USRE45723E1
USRE45723E1 US14/329,255 US200614329255A USRE45723E US RE45723 E1 USRE45723 E1 US RE45723E1 US 200614329255 A US200614329255 A US 200614329255A US RE45723 E USRE45723 E US RE45723E
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amino acid
crystals
medium
particle size
average particle
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Tsuyoshi Shimose
Ryou Ohashi
Katsumi Fujinaga
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Kyowa Hakko Bio Co Ltd
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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
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/04—Alpha- or beta- amino acids
    • C12P13/22—Tryptophan; Tyrosine; Phenylalanine; 3,4-Dihydroxyphenylalanine
    • 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
    • C12P13/06—Alanine; Leucine; Isoleucine; Serine; Homoserine
    • 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
    • C12P13/08—Lysine; Diaminopimelic acid; Threonine; Valine
    • 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
    • C12P13/14—Glutamic acid; Glutamine

Definitions

  • the present invention relates to a process for producing amino acids.
  • a well-known method for producing amino acids is the fermentation method using microorganisms belonging to the genera Corynebacterium, Brevibacterium, Escherichia, Microbacterium, Serratia, Bacillus and Pseudomonas, and the like (non-patent publication No. 1).
  • L-Glu L-glutamic acid
  • patent publication No. 2 a process for crystallizing L-glutamic acid (L-Glu) having a relatively low solubility in a culture medium by using a medium adjusted to pH suitable for deposition of L-Glu
  • patent publication No. 3 a process for depositing ⁇ crystals of L-phenylalanine (L-Phe) in a culture by adding ⁇ crystals of L-Phe to the culture or changing the pH of the culture to a value of 7.8 to 8.3 at the stage where the L-Phe concentration in the culture is beyond the saturation solubility
  • An object of the present invention is to provide a simple process for producing an amino acid with a high production efficiency.
  • the present invention relates to the following (1) to (7).
  • the present invention provides a simple process for producing an amino acid with a high production efficiency.
  • FIG. 1 shows the relationship between the average particle size, specific surface area and total surface area of the crystals of the amino acid added and the form and recovery rate of the crystals of the amino acid accumulated in the medium.
  • the vertical side represents 1000 ⁇ m.
  • microorganisms used in the production process of the present invention are not specifically limited so long as they are microorganisms having the ability to produce an amino acid, and they may be microorganisms isolated from nature or microorganisms having artificially enhanced amino acid productivity.
  • microorganisms having artificially enhanced amino acid productivity include microorganisms obtained by using the following methods alone or in combination:
  • the above microorganisms having the ability to produce an amino acid may be any microorganisms to which the above methods (a) to (e) can be applied or any microorganisms having the above genetic characters. Preferred are procaryotes and more preferred are bacteria.
  • procaryotes include microorganisms belonging to the genera Escherichia, Serratia, Bacillus, Brevibacterium, Corynebacterium, Microbacterium, Pseudomonas, Agrobacterium, Alicyclobacillus, Anabaena, Anacystis, Arthrobacter, Azotobacter, Chromatium, Erwinia, Methylobacterium, Phormidium, Rhodobacter, Rhodopseudomonas, Rhodospirillum, Scenedesmus, Streptomyces, Synechoccus and Zymomonas.
  • Escherichia coli Bacillus subtilis, Bacillus megaterium, Bacillus amyloliquefaciens, Bacillus coagulans, Bacillus licheniformis, Bacillus pumilus, Brevibacterium ammoniagenes, Brevibacterium immariophilum, Brevibacterium saccharolyticum, Brevibacterium flavum, Brevibacterium lactofermentum, Corynebacterium glutamicum, Corynebacterium acetoacidophilum, Microbacterium ammoniaphilum, Serratia ficaria, Serratia fonticola, Serratia liquefaciens, Serratia marcescens, Pseudomonas aeruginosa, Pseudomonas putida, Agrobacterium radiobacter, Agrobacterium rhizogenes, Agrobacterium rubi, Anabaena cylindrica, Anabaena doliolum, Anabaena flosaqua
  • Rhodobacter capsulatus Rhodobacter sphaeroides, Rhodopseudomonas blastica, Rhodopseudomonas marina, Rhodopseudomonas palustris, Rhodospirillum rubrum, Rhodospirillum salexigens, Rhodospirillum salinarum, Streptomyces ambofaciens, Streptomyces aureofaciens, Streptomyces aureus, Streptomyces fungicidicus, Streptomyces griseochromogenes, Streptomyces griseus, Streptomyces lividans, Streptomyces olivogriseus, Streptomyces rameus, Streptomyces tanashiensis, Streptomyces vinaceus and Zymomonas mobilis.
  • Preferred procaryotes include bacteria belonging to the genera Escherichia, Serratia, Bacillus, Brevibacterium, Corynebacterium, Pseudomonas and Streptomyces, for example, the above-mentioned species belonging to the genera Escherichia, Serratia, Bacillus, Brevibacterium, Corynebacterium, Pseudomonas and Streptomyces.
  • More preferred bacteria include Escherichia coli, Corynebacterium glutamicum, Corynebacterium ammoniagenes, Corynebacterium lactofermentum, Corynebacterium flavum, Corynebacterium efficasis, Brevibacterium flavum, Brevibacterium lactofermentum, Bacillus subtilis, Bacillus megaterium, Serratia marcescens, Pseudomonas putida, Pseudomonas aeruginosa, Streptomyces coelicolor and Streptomyces lividans. Particularly preferred are Escherichia coli, Corynebacterium glutamicum and Brevibacterium ammoniagenes.
  • More specific examples include FERM P-4806, ATCC 14751 and ATCC 14752 strains having the ability to produce L-glutamine, ATCC 13005 and ATCC 19561 strains having the ability to produce L-valine, FERM BP-4704 and ATCC 21302 strains having the ability to produce L-leucine, FERM BP-3757 and ATCC 14310 strains having the ability to produce L-isoleucine, ATCC 13281 and MCC 21669 strains having the ability to produce L-phenylalanine, ATCC 21652 strain having the ability to produce L-tyrosine, and DSM 10118, DSM 10121, DSM 10123 and FERM BP-1777 strains having the ability to produce L-tryptophan.
  • the processes for producing amino acids of the present invention include: (1) a process for producing an amino acid which comprises adding crystals of the amino acid having an average particle size of 1 to 120 ⁇ m to a medium so that the concentration of the crystals of the amino acid becomes 0.5 g/l or more, culturing the microorganism having the ability to produce the amino acid of the above 1 in the medium, allowing crystals of the amino acid to form and accumulate in the medium, and recovering the crystals of the amino acid from the culture; and (2) a process for producing an amino acid which comprises adding crystals of the amino acid to a medium so that the total surface area of the crystals of the amino acid in the medium becomes 0.02 m 2 /l or more, culturing the microorganism having the ability to produce the amino acid of the above 1 in the medium, allowing crystals of the amino acid to form and accumulate in the medium, and recovering the crystals of the amino acid from the culture.
  • Culturing of the microorganism in the above medium can be carried out in the same manner as the conventional method used for culturing a microorganism, except for the addition of crystals of an amino acid.
  • any of natural media and synthetic media can be used insofar as it is a medium suitable for efficient culturing of the microorganism which contains carbon sources, nitrogen sources, inorganic salts, etc. which can be assimilated by the microorganism, preferably a liquid medium.
  • any carbon sources that can be assimilated by the microorganism can be used.
  • suitable carbon sources include carbohydrates such as glucose, fructose, sucrose, molasses containing them, starch and starch hydrolyzate; organic acids such as acetic acid and propionic acid; and alcohols such as ethanol and propanol.
  • ammonia ammonium salts of organic or inorganic acids such as ammonium chloride, ammonium sulfate, ammonium acetate and ammonium phosphate, and other nitrogen-containing compounds can be used as well as peptone, meat extract, yeast extract, corn steep liquor, casein hydrolyzate, soybean cake, soybean cake hydrolyzate, and various fermented microbial cells and digested products thereof.
  • organic or inorganic acids such as ammonium chloride, ammonium sulfate, ammonium acetate and ammonium phosphate
  • other nitrogen-containing compounds can be used as well as peptone, meat extract, yeast extract, corn steep liquor, casein hydrolyzate, soybean cake, soybean cake hydrolyzate, and various fermented microbial cells and digested products thereof.
  • inorganic salts examples include potassium dihydrogenphosphate, dipotassium hydrogenphosphate, magnesium phosphate, magnesium sulfate, sodium chloride, ferrous sulfate, manganese sulfate, copper sulfate and calcium carbonate.
  • the crystals of an amino acid to be added in the above process (1) there is no restriction on the average particle size, the amount, the kind of amino acid, the kind of crystal form, etc. of the crystals so far as they are crystals of an amino acid having an average particle size of 1 to 120 ⁇ m which can give a medium having a crystal concentration of 0.5 g/l or more.
  • the average particle size of the crystals of an amino acid to be added is 1 to 120 ⁇ m, preferably 2 to 110 ⁇ m, more preferably 5 to 70 ⁇ m, further preferably 7 to 50 ⁇ m, particularly preferably 10 to 35 ⁇ m, and most preferably 11 to 13 ⁇ m.
  • the amount of the crystals of an amino acid is such that the concentration of the crystals of the amino acid in the medium after the addition thereof becomes 0.5 g/l or more, preferably 2 to 30 g/l, more preferably 3 to 25 g/l, further preferably 4 to 22 g/l, particularly preferably 5 to 20 g/l, and most preferably 5.5 to 16.5 g/l.
  • the combination is an average particle size of 1 to 120 ⁇ m and an amount giving a medium having a crystal concentration of 0.5 g/l or more, preferably an average particle size of 2 to 110 ⁇ m and an amount giving a medium having a crystal concentration of 2 to 30 g/l, more preferably an average particle size of 5 to 70 ⁇ m and an amount giving a medium having a crystal concentration of 3 to 25 g/l, further preferably an average particle size of 7 to 50 ⁇ m and an amount giving a medium having a crystal concentration of 4 to 22 g/l, particularly preferably an average particle size of 10 to 35 ⁇ m and an amount giving a medium having a crystal concentration of 5 to 20 g/l, and most preferably an average particle size of 11 to 13 ⁇ m and an amount giving a medium having a crystal concentration of 5.5 to 16.5 g/l.
  • the crystals of an amino acid may be added to the medium before inoculating the microorganism having the ability to produce the amino acid or may be added at any time during the culturing period after inoculation of the microorganism having the ability to produce the amino acid.
  • the crystals are added preferably at some time after the microorganism having the ability to produce the amino acid is inoculated in the medium, between around the time when the amino acid concentration in the medium reaches the saturation solubility and the time when crystals of the amino acid deposit in the medium, more preferably at some time after the amino acid concentration in the medium reached the saturation solubility and before crystals of the amino acid deposit in the medium, further preferably at some time when the medium is supersaturated with the amino acid and before crystals of the amino acid deposit in the medium.
  • “before crystals of the amino acid deposit in the medium” refers preferably to the period during which the presence of amino acid crystals is not observed at all in the medium; however, deposition of a slight amount of amino acid crystals is allowable insofar as the effect of the present invention can be achieved in respect of the crystal recovery rate and the like.
  • the amount of the crystals to be added is 0.5 g/l or more, preferably 2 to 30 g/l, more preferably 3 to 25 g/l, further preferably 4 to 22 g/l, particularly preferably 5 to 20 g/l, most preferably 5.5 to 16.5 g/l based on the amount of the medium at the time of addition.
  • the combination of the average particle size of the crystals of an amino acid to be added and addition amount thereof are as follows: the combination is an average particle size of 1 to 120 ⁇ m and an amount of 0.5 g/l or more based on the amount of the medium at the time of addition, preferably an average particle size of 2 to 110 ⁇ m and an amount of 2 to 30 g/l, more preferably an average particle size of 5 to 70 ⁇ m and an amount of 3 to 25 g/l, further preferably an average particle size of 7 to 50 ⁇ m and an amount of 4 to 22 g/l, particularly preferably an average particle size of 10 to 35 ⁇ m and an amount of 5 to 20 g/l, and most preferably an average particle size of 11 to 13 ⁇ m and an amount of 5.5 to 16.5 g/l.
  • the crystals to be added are crystals such that the total surface area of the crystals in the medium after addition becomes 0.02 m 2 /l or more, preferably 0.08 to 70 m 2 /l, more preferably 0.2 to 23 m 2 /l, further preferably 0.4 to 15 m 2 /l, particularly preferably 0.7 to 9.3 m 2 /l, most preferably 2.0 to 7.0 m 2 /l.
  • examples of the crystals of an amino acid to be added in the above process (2) include crystals having an average particle size of 1 to 120 ⁇ m and giving a medium having a crystal concentration of 0.5 g/l or more, preferably having an average particle size of 2 to 110 ⁇ m and giving a medium having a crystal concentration of 2 to 30 g/l, more preferably having an average particle size of 5 to 70 ⁇ m and giving a medium having a crystal concentration of 3 to 25 g/l, further preferably having an average particle size of 7 to 50 ⁇ m and giving a medium having a crystal concentration of 4 to 22 g/l, particularly preferably having an average particle size of 10 to 35 ⁇ m and giving a medium having a crystal concentration of 5 to 20 g/l, and most preferably having an average particle size of 11 to 13 ⁇ m and giving a medium having a crystal concentration of 5.5 to 16.5 g/l.
  • the time for addition of the crystals of an amino acid to the medium is the same as in the above process (1).
  • the crystals of the amino acid to be added are crystals such that the total surface area of the crystals calculated based on the amount of the medium at the time of addition is 0.02 m 2 /l or more, preferably 0.08 to 70 m 2 /l, more preferably 0.2 to 23 m 2 /l, further preferably 0.4 to 15 m 2 /l, particularly preferably 0.7 to 9.3 m 2 /l, most preferably 2.0 to 7.0 m 2 /l.
  • examples of the crystals of an amino acid include crystals having an average particle size of 1 to 120 ⁇ m whose amount based on the amount of the medium at the time of addition is 0.5 g/l or more, preferably crystals having an average particle size of 2 to 110 ⁇ m whose amount based on the amount of the medium at the time of addition is 2 to 30 g/l, more preferably crystals having an average particle size of 5 to 70 ⁇ m whose amount based on the amount of the medium at the time of addition is 3 to 25 g/l, further preferably crystals having an average particle size of 7 to 50 ⁇ m whose amount based on the amount of the medium at the time of addition is 4 to 22 g/l, particularly preferably crystals having an average particle size of 10 to 35 ⁇ m whose amount based on the amount of the medium at the time of addition is 5 to 20 g/l, and most preferably crystals having an average particle size of 11 to 13 ⁇ m whose amount based on the amount of the medium at the time of addition is is
  • the amount of the medium in the culture may be measured by any known method.
  • the amount of the medium can be measured by separating the medium and insoluble matters such as microbial cells by centrifuging the culture, measuring the volume of the sedimented insoluble matters, and then subtracting the measured volume from the amount of the culture.
  • the crystals of an amino acid to be added in the above processes (1) and (2) include crystals having an average specific surface area of 0.06 m 2 /cm 3 or more, preferably 0.07 to 7.2 m 2 /cm 3 , more preferably 0.07 to 1.43 m 2 /cm 3 , further preferably 0.1 to 1.0 m 2 /cm 3 , particularly preferably 0.14 to 0.72 m 2 /cm 3 .
  • the amino acid to be added in the above processes (1) and (2) may be any amino acid that can be produced by a microorganism, but is preferably an amino acid selected from the group consisting of L-glutamine, L-valine, L-leucine, L-isoleucine, L-phenylalanine, L-tyrosine and L-tryptophan, more preferably an amino acid selected from the group consisting of L-glutamine, L-valine and L-leucine, further preferably L-glutamine.
  • ⁇ crystals of L-phenylalanine may be excluded from the crystals of an amino acid to be added in the process of the present invention.
  • the crystals of an amino acid to be added to a medium in the present invention can be obtained as commercially available products or by using known methods such as the fermentation method and purification method.
  • the crystals can also be obtained by preparing crystals of an amino acid having a desired average particle size by crushing commercially available amino acid crystals or amino acid crystals obtained by the above known methods by using commercially available mills, e.g., M4 Jiyu Mill (Nara Machinery Co., Ltd.), Atomizer TAP-20 (Tokyo Atomizer Mfg. Co., Ltd.) and Air Classifying Mill (Hosokawa Micron Powder Systems).
  • crystals of an amino acid having an average particle size of about 45 ⁇ m can be obtained by crushing crystals of an amino acid having an average particle size of about 110 ⁇ m which are obtained by a known fermentation method and purification method using M4 Jiyu Mill under the following conditions: screen, ⁇ 1.0 mm; rotation, 4500 rpm; speed, ca. 400 kG/h.
  • crystals of an amino acid having an average particle size of about 11 ⁇ m can be obtained by crushing the crystals obtained by the above crushing treatment under the following conditions: screen, ⁇ 0.3 mm; rotation, 6000 rpm; speed, ca. 200 kG/h.
  • the specific surface area of crystals of an amino acid can be measured by using commercially available analyzers, e.g., SK LASER MICRON SIZER LMS-24 (particle distribution analyzer by the laser diffraction and scattering method, produced by Seishin Enterprise Co., Ltd.). In the measurement of the specific surface area of crystals of an amino acid, it is preferable to calculate the specific surface area assuming that the crystals are spherical and are similar in shape.
  • the total surface area of crystals of an amino acid can be calculated from the specific surface area of the crystals and the addition amount thereof.
  • Culturing is usually carried out under aerobic conditions, for example, by shaking culture or submerged spinner culture under aeration.
  • the culturing temperature is preferably 15 to 40° C., and the culturing period is usually 5 hours to 7 days.
  • the pH is maintained at 3.0 to 9.0 during the culturing.
  • the pH adjustment is carried out by using an organic or inorganic acid, an alkali solution, urea, calcium carbonate, ammonia, etc.
  • antibiotics such as ampicillin and tetracycline may be added to the medium during the culturing.
  • an inducer may be added to the medium, if necessary.
  • an inducer may be added to the medium, if necessary.
  • an inducer may be added to the medium, if necessary.
  • an expression vector comprising lac promoter isopropyl- ⁇ -D-thiogalactopyranoside or the like may be added to the medium; and in the case of a microorganism transformed with an expression vector comprising trp promoter, indoleacrylic acid or the like may be added.
  • the amino acid accumulated in the medium in the above processes may be any amino acid that can be produced by a microorganism, and is preferably an amino acid selected from the group consisting of L-glutamine, L-valine, L-leucine, L-isoleucine, L-phenylalanine, L-tyrosine and L-tryptophan, more preferably an amino acid selected from the group consisting of L-glutamine, L-valine and L-leucine, further preferably L-glutamine.
  • the crystals of an amino acid accumulated in the medium in the above processes include crystals having an average particle size of 15 ⁇ m or more, preferably 20 ⁇ m or more, more preferably 30 ⁇ m or more, further preferably 40 ⁇ m or more, particularly preferably 50 ⁇ m or more, most preferably 60 ⁇ m or more.
  • recovery of the crystals of an amino acid in the culture can be carried out by any ordinary method for purification of amino acids.
  • the crystals of an amino acid are separated and purified by directly separating the crystals and the microbial cells in the culture after the completion of culturing by utilizing the difference in particle size and specific gravity between them.
  • the above separation and purification of crystals of an amino acid utilizing the difference in particle size and specific gravity can be carried out by known methods such as the gravitational classification method and the centrifugal classification method.
  • crystals of an amino acid can be obtained with a high recovery rate.
  • the crystals can be further purified by ordinary methods using active carbon, ion-exchange resins, etc. or by means such as extraction with an organic solvent, crystallization, thin layer chromatography and high performance liquid chromatography.
  • Corynebacterium glutamicum ATCC 14752 was cultured in a production medium (250 g/l glucose, 30 g/l NH 4 Cl, 1.0 g/l K 2 HPO 4 , 1.0 g/l KH 2 PO 4 , 0.5 g/l MgSO 4 .7H 2 O, 20 mg/l FeSO 4 , 2 mg/l MnSO 4 .4H 2 O, 10 ⁇ g/l biotin and 1 mg/l thiamine hydrochloride, pH 6.8) in a 500-l jar fermenter with appropriate adjustment of pH and temperature.
  • a production medium 250 g/l glucose, 30 g/l NH 4 Cl, 1.0 g/l K 2 HPO 4 , 1.0 g/l KH 2 PO 4 , 0.5 g/l MgSO 4 .7H 2 O, 20 mg/l FeSO 4 , 2 mg/l MnSO 4 .4H 2 O, 10 ⁇ g/l biotin and 1 mg/l
  • Example 2 Culturing was carried out in the same manner as in Example 1, except that crystals of L-glutamine having the average particle size shown in FIG. 1 were used as the crystals to be added to the medium, and crystals of L-glutamine were obtained.
  • the specific surface area of crystals of L-glutamine was measured using SK LASER MICRON SIZER LMS-24 (particle distribution analyzer by the laser diffraction and scattering method, produced by Seishin Enterprise Co., Ltd.). In the measurement of the specific surface area of crystals of L-glutamine, the calculation was made assuming that the crystals are spherical and are similar in shape.
  • FIG. 1 shows the form of the crystals of L-glutamine added and the crystals of L-glutamine obtained by fermentation, and the recovery rate, dry content, etc. of the crystals of L-glutamine.
  • the particle size of crystals of an amino acid deposited in the medium during the culturing can be controlled by adding crystals of the amino acid to the medium to keep the degree of supersaturation of the amino acid in the medium below a certain level and to allow an appropriate number of crystals of the amino acid to be present in the medium as seed crystals, that is, by adjusting the average particle size and the amount or the total surface area of the crystals of the amino acid to be added to the medium, and as a result, crystals of the amino acid which are easily separable from microbial cells can be obtained with a high recovery rate.
  • amino acids can be efficiently produced in a simple manner.

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TWI361834B (en) 2005-04-12 2012-04-11 Kyowa Hakko Bio Co Ltd A method for producing amino acids
JP2010110216A (ja) 2007-02-20 2010-05-20 Ajinomoto Co Inc Ｌ−アミノ酸または核酸の製造方法
US9227916B2 (en) 2011-09-12 2016-01-05 Kyowa Hakko Bio Co., Ltd. Process for producing amino acid
KR102402639B1 (ko) 2017-11-24 2022-05-26 삼성전자주식회사 전자 장치 및 그의 통신 방법
CN113025667B (zh) * 2020-12-31 2022-10-25 安徽华恒生物科技股份有限公司 一种氨基酸发酵培养基的制备方法及其应用

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