Method for producing tyrosine from fermentation broth

Abstract

The present invention relates to a method for producing high-purity tyrosine from a fermentation broth containing tyrosine produced by microbial fermentation, the method comprising the steps of: adding a basic solution to dissolve tyrosine and obtain a tyrosine solution; performing simultaneous neutralization crystallization to obtain primary tyrosine crystals; adding a base to the primary tyrosine crystals to dissolve them and obtain a re-dissolved tyrosine solution; and adding an acid to the re-dissolved tyrosine solution to perform simultaneous neutralization crystallization to obtain secondary tyrosine crystals.

Description

[Technical Field]

[0001] The present invention relates to a method for producing highly purified tyrosine from a fermentation broth containing tyrosine produced by microbial fermentation. [Background technology]

[0002] Tyrosine is an essential amino acid that has the lowest solubility in water among amino acids due to its polar hydroxyphenyl group, and when it crystallizes in water, it has a needle-like or plate-like crystalline structure.

[0003] Tyrosine is produced by hydrolysis, chemical synthesis, enzymatic methods, or microbial fermentation.

[0004] As disclosed in Patent Document 1, tyrosine is generally produced from animal hair or the like by hydrolyzing proteins followed by bleaching and crystallization. Tyrosine can also be produced by chemical synthesis, but DL-tyrosine is produced during the production process, and a complex separation process is required to obtain L-tyrosine, making this method unsuitable for industrial use.

[0005] The enzymatic method can produce tyrosine using phenol, pyruvic acid, ammonia, or phenol and L-serine as starting materials through the catalytic action of tyrosine phenolase, but there is a lack of technology to regulate the activity of the enzyme during the reaction.

[0006] Microbial fermentation is a method for producing L-tyrosine through the fermentation of microbial strains using a carbon source such as glucose or raw sugar as a raw material. However, it requires the separation and purification of tyrosine from the fermentation broth containing tyrosine. Patent Document 2 discloses a method for extracting tyrosine from fermentation broth, but because it uses aqueous ammonia to dissolve the crystals in the fermentation broth, it is difficult to produce a highly concentrated tyrosine solution. Therefore, additional concentration is required for crystallization. Conventional neutralization methods, such as neutralization by slowly adding acid under basic conditions, produce thin, needle-like tyrosine, but the separated wet crystals have a high moisture content, resulting in a product with a low content (below 98%).

[0007] Therefore, there remains a need for a method that can efficiently produce tyrosine with high purity. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] U.S. Patent No. 2,650,242 [Patent Document 2] China application CN111039808A Summary of the Invention [Problem to be solved by the invention]

[0009] The present inventors have conducted research into a method for efficiently separating and purifying high-purity and high-quality tyrosine from a fermentation broth containing tyrosine, and have developed a method for producing high-purity tyrosine crystals by dissolving tyrosine in a basic compound.

[0010] An object of the present invention is to provide a method for producing highly pure and high quality tyrosine from a microbial fermentation broth.

[0011] Another object of the present invention is to provide tyrosine crystals produced from a microbial fermentation broth. [Means for solving the problem]

[0012] One aspect of the present invention is a method for producing tyrosine from a microbial fermentation broth, comprising the steps of: adding a basic solution to the microbial fermentation broth containing tyrosine to obtain a tyrosine crystal slurry as a tyrosine solution; adding an acid to the tyrosine solution to neutralize and crystallize the solution to obtain primary tyrosine crystals; adding a basic solution to the primary tyrosine crystals to obtain a tyrosine redissolved solution; and and adding an acidic solution to the tyrosine redissolution solution to obtain secondary tyrosine crystals by neutralization crystallization.

[0013] The term "microbial fermentation broth" used in this specification means a microbial culture broth containing tyrosine produced by culturing a microorganism capable of producing tyrosine, and may include a slurry in which tyrosine separated from the microbial culture broth is dispersed in water.

[0014] As used herein, the term "tyrosine solution" refers to a solution obtained by dissolving tyrosine, which has low solubility in water, in a basic solution such as a strong base. The term "tyrosine re-dissolution solution" refers to a solution obtained by adding a strong base to tyrosine crystals obtained after primary crystallization and dissolving them.

[0015] As used herein, the term "neutralization crystallization" refers to crystallization of a substance that is poorly soluble or insoluble in water depending on the pH by reacting it with an acid or base in the presence of water. "Simultaneous neutralization crystallization" refers to simultaneous addition of a tyrosine solution to be crystallized and an acid to a vessel such as a crystallization tube or a crystallization tank, and mixing them while maintaining a specific pH to precipitate crystals.

[0016] In one embodiment of the present invention, the microbial fermentation broth is obtained by fermentation of a microorganism capable of producing tyrosine, and the fermentation may be carried out by fed-batch culture, batch culture, repetitive fed-batch culture, or continuous culture. The fermentation medium used may be optimized depending on the producing strain.

[0017] In one embodiment of the present invention, the step of obtaining the tyrosine solution may include adding a basic solution until the pH reaches 11 to 12. A strong base may be added directly to the microbial fermentation broth containing tyrosine, or a base, for example, 20% to 50% or 40% NaOH or KOH, may be added to a slurry obtained by adding water to tyrosine recovered by high-speed centrifugation of the microbial fermentation broth, to obtain a tyrosine solution at a pH of 11 to 12. Since tyrosine has low solubility in water, it can be dissolved at a high concentration by adding a strong basic solution such as NaOH or KOH.

[0018] In one embodiment of the present invention, the step of obtaining the primary tyrosine crystals may include simultaneously adding the tyrosine dissolving solution and the acidic solution to a crystallization tank and adjusting the pH of the mixed solution to within a range of 5 to 7.

[0019] In one embodiment of the present invention, the step of obtaining the tyrosine redissolution solution may include adding a basic solution to the primary tyrosine crystals so that the pH of the mixed solution becomes 11 or more, thereby dissolving the primary tyrosine crystals.

[0020] In one embodiment of the present invention, the step of obtaining the secondary tyrosine crystals may involve performing neutralization crystallization by simultaneously adding the tyrosine redissolution solution and an acidic solution and adjusting the pH of the mixed solution to pH 5 to 7.

[0021] In one embodiment of the present invention, the secondary neutralization crystallization may be carried out at 60 to 80°C or 70 to 80°C.

[0022] In one embodiment of the present invention, the secondary neutralization crystallization may be carried out by heating the tyrosine solution or redissolved tyrosine solution to 60 to 80°C and adding a dilute acidic solution to adjust the pH to 5 to 6, or to 5.5.

[0023] In one embodiment of the present invention, the microbial fermentation broth may be a culture broth containing 35 g / L or more of tyrosine produced by culturing a strain capable of producing tyrosine, or may be a slurry obtained by adding water to tyrosine crystals recovered by high-speed centrifugation of the culture broth.

[0024] In one embodiment of the present invention, high-speed centrifugation for recovering tyrosine from the microbial fermentation broth may be carried out at 1,000 to 5,000 G using a decanter.

[0025] In one embodiment of the present invention, the high-speed centrifugation for recovering tyrosine from the microbial fermentation broth may be carried out at 2,000 G or more.

[0026] In one embodiment of the present invention, the method may further comprise the step of filtering the tyrosine solution to obtain a filtrate before the step of obtaining the primary tyrosine crystals.

[0027] In one embodiment of the present invention, the method may further comprise the step of subjecting the filtrate to ultrafiltration.

[0028] In one embodiment of the present invention, the step of obtaining a filtrate from the tyrosine dissolution solution includes filtering the tyrosine dissolution solution using a 0.1 micron ceramic filter membrane to remove cellular components, and may further include passing the filtrate through an ultrafiltration (UF) membrane D1000-500,000 to further remove protein components and the like from the filtrate.

[0029] In one embodiment of the present invention, the strong basic solution may be NaOH or KOH, and may be used at a concentration of 20-50%, or at a concentration of 40%.

[0030] In one embodiment of the present invention, the acid solution may be acetic acid, hydrochloric acid, nitric acid or sulfuric acid, and may be used at a concentration of 40% or less.

[0031] In one embodiment of the present invention, the method may further comprise the step of decolorizing the tyrosine reconstitution solution before the step of harvesting the secondary tyrosine crystals.

[0032] In one embodiment of the present invention, the UV-VIS absorbance of the decolorized tyrosine redissolution solution may be 0.0001 to 0.1 at 430 nm, for example, 0.05 or less.

[0033] In one embodiment of the present invention, the decolorizing step may include the steps of filtering the tyrosine redissolved solution to obtain a filtrate, and adding activated carbon to the filtrate to decolorize the tyrosine redissolved solution to obtain a decolorized redissolved solution.

[0034] In one embodiment of the present invention, the decolorizing step may further include passing the decolorized redissolved solution through a basic anion exchange resin to further decolorize the solution.

[0035] In one specific example of the present invention, in order to remove the color of the redissolved tyrosine solution, activated carbon may be added to the redissolved tyrosine solution, and the solution may be treated at 60°C for about 1 hour, filtered through a filter press, and then passed through a basic anion resin column.

[0036] In one embodiment of the present invention, the method may further comprise the steps of filtering the obtained reaction solution using a basket centrifuge after neutralizing and crystallizing the tyrosine redissolved solution, and washing the tyrosine crystals with water equivalent to 20% of the filtration volume.

[0037] In one embodiment of the present invention, the tyrosine produced by the method may be needle-like crystals with a crystal size of 70 microns or more and a water content of 15% or less.

[0038] In one embodiment of the present invention, the method may further comprise the step of drying the obtained tyrosine crystals in a fluidized bed dryer to a moisture content of 0.5% or less.

[0039] Another aspect of the present invention provides needle-shaped tyrosine crystals having a size of 70 microns or more and a moisture content of 15% or less, obtained by dissolving tyrosine in a microbial fermentation broth by adding a strong base and simultaneously neutralizing and crystallizing the tyrosine. In particular embodiments, for example, the following items are provided: (Item 1) adding a basic solution to the microbial fermentation broth containing tyrosine to obtain a tyrosine solution; adding an acidic solution to the tyrosine solution to neutralize and crystallize the solution to obtain primary tyrosine crystals; adding a basic solution to the primary tyrosine crystals to obtain a redissolved tyrosine solution; and a step of adding an acidic solution to the tyrosine redissolution solution to obtain secondary tyrosine crystals by neutralization crystallization. (Item 2) 2. The method for producing tyrosine according to item 1, wherein the step of obtaining the tyrosine solution comprises adding a basic solution to the tyrosine solution so that the pH of the tyrosine solution becomes 11 or higher. (Item 3) 2. The method for producing tyrosine according to item 1, wherein the step of obtaining primary tyrosine crystals comprises simultaneously adding the tyrosine dissolving solution and the acidic solution to a crystallization tank and adjusting the pH of the mixed solution to within a range of 5 to 7. (Item 4) 2. The method for producing tyrosine according to item 1, wherein the step of obtaining the tyrosine redissolution solution comprises adding a basic solution to the primary tyrosine crystals so that the pH of the mixed solution becomes 11 or more, thereby dissolving the primary tyrosine crystals. (Item 5) 2. The method for producing tyrosine according to item 1, wherein the step of obtaining the secondary tyrosine crystals comprises simultaneously adding the tyrosine redissolution solution and an acidic solution, adjusting the pH of the mixed solution to 5 to 7, and performing neutralization crystallization. (Item 6) Item 6. The method for producing tyrosine according to Item 5, wherein the neutralization crystallization is carried out at 70 to 80°C. (Item 7) 2. The method for producing tyrosine according to item 1, further comprising the step of filtering the tyrosine solution to obtain a filtrate before the step of obtaining the primary tyrosine crystals. (Item 8) 8. The method for producing tyrosine according to Item 7, further comprising ultrafiltration of the filtrate. (Item 9) Item 2. The method for producing tyrosine according to Item 1, wherein the basic solution contains at least one selected from the group consisting of NaOH and KOH. (Item 10) Item 2. The method for producing tyrosine according to Item 1, wherein the acidic solution contains at least one selected from the group consisting of acetic acid, hydrochloric acid, nitric acid, and sulfuric acid. (Item 11) 2. The method for producing tyrosine according to item 1, further comprising the step of decolorizing the tyrosine redissolution solution before the step of obtaining the secondary tyrosine crystals. (Item 12) Item 11. The method for producing tyrosine according to Item 10, wherein the decolorizing step comprises: filtering the redissolved tyrosine solution to obtain a filtrate; and adding activated carbon to the filtrate to decolorize the filtrate, thereby obtaining a decolorized redissolved tyrosine solution. (Item 13) Item 13. The method for producing tyrosine according to Item 12, wherein the decolorizing step further comprises passing the decolorized redissolved solution through a basic anion exchange resin to further decolorize it. (Item 14) Item 2. The method for producing tyrosine according to Item 1, wherein the tyrosine produced by the method for producing tyrosine is a needle-shaped crystal having a crystal size of 70 microns or more and a water content of 15% or less. [Effects of the Invention]

[0040] The method according to one embodiment of the present invention can produce highly pure, needle-shaped tyrosine crystals by dissolving tyrosine crystals produced in a high-concentration fermentation process in strong alkali without adding additional water, thereby reducing the capacity of storage tanks and decolorization equipment required in the purification process and reducing the energy costs required for concentration in known techniques. Furthermore, the method according to one embodiment of the present invention can reduce the moisture content of the separated wet crystals in the crystallization process for commercialization, making it possible to easily produce highly pure (98.5% or higher) tyrosine crystals. [Brief explanation of the drawings]

[0041] [Figure 1] 1 shows a flow chart of the steps for obtaining primary tyrosine crystals from a tyrosine fermentation broth in one embodiment of the method of the present invention. [Figure 2] 1 shows a flow chart of steps for obtaining secondary tyrosine crystals from primary tyrosine crystals in one embodiment of the method of the present invention. [Figure 3] (a) Primary tyrosine crystals obtained according to one embodiment of the present invention and (b) primary tyrosine crystals obtained according to a comparative example (Patent Document 2). [Figure 4] (a) Secondary tyrosine crystals obtained according to one embodiment of the present invention and (b) secondary tyrosine crystals obtained according to a comparative example (Patent Document 2). DETAILED DESCRIPTION OF THE INVENTION

[0042] The present application will be described in more detail below with reference to examples. However, these examples are merely illustrative of one or more specific examples, and the scope of the present invention is not limited to these examples.

[0043] Example 1. Production of tyrosine crystals from tyrosine fermentation broth In this example, a highly concentrated tyrosine solution was obtained from a fermentation broth containing tyrosine, which has low water solubility, and then crystallized to produce tyrosine crystals.

[0044] (1) Tyrosine solubility Because tyrosine has low solubility in water, a base was added to obtain a highly concentrated solution. The input amount, pH, and tyrosine solubility of fermentation broth containing tyrosine were compared using 30% ammonia and 50% NaOH. The results are shown in Table 1 below. [Table 1]

[0045] When 50% NaOH was used to obtain a highly concentrated tyrosine solution, a smaller amount of ammonia was added than when 30% ammonia was used, and a highly concentrated tyrosine solution could be obtained.

[0046] (2) Preparation of tyrosine solution In this example, Corynebacterium glutamicum CM06-0112 (KCCM12708P), a Corynebacterium-based strain capable of producing tyrosine at high concentrations and with high productivity, was cultured in batch culture for 60 hours to produce a fermentation broth containing tyrosine. The tyrosine concentration in the fermentation broth was adjusted to 85 g / L.

[0047] As confirmed in (1), a strong basic solution (50% NaOH or 50% KOH) was added to the tyrosine fermentate obtained by fermentation to produce a highly concentrated tyrosine solution, which was then passed through a ceramic membrane to remove any remaining cellular components and proteins.

[0048] In order to produce high-purity (98.5% or more) tyrosine crystals from the fermentation broth obtained by fermenting a strain capable of producing tyrosine, two crystallization steps were required.

[0049] (3) Primary crystallization of tyrosine solution Primary crystallization is a crystallization process to effectively remove other amino acids and ionic components contained in the fermentation broth. In (2), a strongly basic solution is added to dissolve tyrosine, and the cells are removed. The basic tyrosine solution obtained by removing the cells is then simultaneously added to a crystallization tank containing easily mixable purified water and a dilute sulfuric acid solution. The pH is instantly adjusted to 5-7, and granular tyrosine crystals are obtained through simultaneous neutralization and crystallization. The tyrosine crystals thus formed settle easily and have the advantage of exhibiting a lower wet crystal moisture content and higher purity than conventional crystallization processes. To compare this simultaneous neutralization crystallization with isoelectric (droplet) neutralization crystallization, isoelectric crystallization was performed at pH 5.7 by slowly adding an acid solution (hydrochloric acid or acetic acid) to a cell-free alkaline eutectic solution, as described in Patent Document 2. The tyrosine crystals produced by simultaneous neutralization crystallization were granular, large in size, easy to separate, and had a high tyrosine content. However, isoelectric neutralization crystallization produced very small, thin tyrosine crystals that were difficult to separate from the solution, resulting in a low tyrosine content. Table 2 below shows the wet crystal moisture, crystal size, and content for each primary crystallization method, and Figures 3(a) and (b) show the crystal morphology. [Table 2]

[0050] The crystals isolated by primary crystallization had a purity level of 95% (HPLC standard) and a crystal recovery rate of 97%. Decolorization and additional crystallization processes were required to produce a tyrosine product of food and pharmaceutical quality.

[0051] (4) Decolorization and secondary crystallization of tyrosine solution The primary tyrosine crystals obtained in (3) were redissolved in a strong base solution to obtain a tyrosine redissolved solution, which was then decolorized using activated carbon and anionic resin.

[0052] Pure tyrosine crystals are very small, needle-shaped crystals. Neutralization crystallization, which proceeds slowly from basic to neutral, poses the problem of high moisture content during crystal separation, making drying difficult due to the high moisture content of the wet crystals. To overcome this problem, we developed a crystallization process that increases the thickness of the crystals while maintaining the tyrosine crystal form, thereby producing high-purity tyrosine with low moisture content. Specifically, to increase the thickness of the tyrosine crystals, a crystallization tank containing purified water for stirring was heated to 70-80°C. Then, the decolorized tyrosine reconstituted solution and dilute acid (H2SO4, HCl, AcOH) were simultaneously added, and the pH of the tyrosine reconstituted solution was instantly adjusted to 5-7, producing needle-shaped, thicker tyrosine crystals. These were then collected in a basket centrifuge and dried to produce high-purity food-grade tyrosine.

[0053] Similarly to (3), to compare simultaneous neutralization crystallization and isoelectric neutralization crystallization, isoelectric crystallization was performed at pH 5.7 by slowly adding an acid solution (hydrochloric acid or acetic acid) to the alkaline eutectic solution from which the cells had been removed, as described in Patent Document 2.

[0054] The properties of the crystals obtained by simultaneous neutralization crystallization and isoelectric crystallization of the decolorized reconstituted solution are shown in Table 3, and the morphology of the crystals is shown in Figures 4(a) and (b), respectively. [Table 3]

[0055] Example 2. Dissolving high concentration tyrosine crystals in fermentation broth The tyrosine crystals were dissolved under conditions determined based on the results of Example 1.

[0056] Specifically, 5000 ml of tyrosine fermentation broth (80 g / L) was placed in a flask equipped with a thermometer and a stirrer and stirred at 30° C. The pH of the fermentation broth was at the 6.5-7.0 level, and when 220 ml of a strong base, 50% NaOH or 50% KOH, was added, the color of the fermentation broth turned dark brown at a pH of 11.0, and all the crystals were dissolved (69.6 g / L).

[0057] When 1240 ml of 30% aqueous ammonia, a weak base, was added instead of 220 ml of 50% NaOH or 50% KOH, a strong base, the pH of the eutectic solution was at the 10.5 level, the solubility of tyrosine at this time was 24.3 g / L, and all of the tyrosine crystals in the fermentation broth could not be dissolved.

[0058] Table 4 shows the solubility of tyrosine as a function of pH in solution. [Table 4]

[0059] When a weak base is used to dissolve tyrosine, an excessive amount must be administered, which is inefficient because the solubility of tyrosine crystals is lower compared to the amount administered than when a strong base is used.

[0060] Example 3. Primary crystallization with primary simultaneous neutralization As described in Example 2, the fermentation broth containing dissolved tyrosine crystals was heated to 55°C by adding a strong base, and then cells were removed using equipment (TAMI INDUSTRIES) equipped with a 0.12 micro ceramic membrane filter at 2 bar to prepare a tyrosine solution (75 g / L) for crystallization.

[0061] 1000 ml of purified water was added to a 10,000 ml crystallization tube equipped with a thermometer, a stirrer, and a pH meter (METTLER TOLEDO), and the mixture was stirred at 30°C. 5000 ml of tyrosine solution and 420 ml of 32% sulfuric acid were simultaneously and continuously added to the crystallization tube using two metering pumps for 1 or 2 hours to maintain the pH in the crystallization tube at 5.0 to 7.0.

[0062] After the addition of the tyrosine dissolving solution and sulfuric acid was completed, the mixture was further stirred for about 30 minutes, and the crystals were separated using a basket centrifuge (KOKUSAN H-122) at 1500 rpm for 10 minutes. The lye adhering to the crystal surface was washed with 500 ml of purified water, yielding 560 g of primary tyrosine crystals (yield 93%).

[0063] FIG. 1 shows a schematic diagram of the method for obtaining primary tyrosine crystals from a tyrosine fermentation broth.

[0064] The moisture content of the obtained crystals was 30% based on LOD (Loss on Drying) at 105°C, and the content was 95.8% based on HPLC.

[0065] Example 4. Secondary Crystallization Method with Secondary Simultaneous Neutralization 560 g of the tyrosine primary crystals obtained in Example 3 was added to 4000 ml of purified water and heated to 55°C. 50% NaOH was added to completely dissolve the crystals at pH 11.0-11.5, yielding a tyrosine reconstituted solution. To remove color and protein components from the secondary crystallization solution, 0.4% activated carbon was added to the reconstituted solution, stirred for 1 hour, and then filtered using GF / F (Whatman Glass Microfiber Filters). The resulting filtrate was passed through a strongly basic anion resin column (TRILITE AMP26) again to produce a tyrosine reconstituted solution for secondary crystallization. The tyrosine concentration of the obtained tyrosine reconstituted solution for crystallization, which was the crystallization feed, was 35 g / L, and the absorbance measured at 430 nm using a UV-VIS spectrophotometer was 0.02.

[0066] 1000 ml of purified water was added to a 10,000 ml crystallization tube equipped with a thermometer, stirrer, and pH meter, and the mixture was stirred at 75°C. Using two metering pumps, 5000 ml of the crystallization feed prepared above and 480 ml of 32% sulfuric acid were continuously added for 3 hours to maintain the pH in the crystallization tube at 6.0. After the addition of the crystallization feed was completed, the temperature of the feed was lowered to 55°C, and the mixture was separated using a basket centrifuge (KOKUSAN H-122) at 1500 rpm for 10 minutes to obtain 380 g of primary tyrosine crystals (yield 91%).

[0067] FIG. 2 shows a schematic diagram of the method for obtaining tyrosine crystals.

[0068] The moisture content of the obtained crystals was 10% based on LOD at 105°C, and the content was 99.0% based on HPLC.

Claims

1. adding a basic solution to the microbial fermentation broth containing tyrosine to obtain a tyrosine solution; a step of adding an acidic solution to the tyrosine solution to simultaneously neutralize and crystallize the tyrosine solution to obtain primary tyrosine crystals, wherein the step of simultaneously neutralizing and crystallizing the tyrosine solution and the acidic solution is carried out by simultaneously adding the tyrosine solution and the acidic solution to a crystallization tube or a crystallization tank, mixing the solution, and adjusting the pH of the mixed solution to within a range of 5 to 7; adding a basic solution to the primary tyrosine crystals to obtain a redissolved tyrosine solution; and a step of adding an acidic solution to the tyrosine re-dissolution solution to obtain secondary tyrosine crystals by simultaneous neutralization crystallization, wherein the step of obtaining secondary tyrosine crystals comprises simultaneously adding the tyrosine re-dissolution solution and the acidic solution to a crystallization tube or a crystallization tank, mixing the solution, and adjusting the pH of the mixed solution to within a range of 5 to 7 to perform simultaneous neutralization crystallization. A method for producing tyrosine, comprising:

2. 2. The method for producing tyrosine according to claim 1, wherein the step of obtaining the tyrosine solution comprises adding a basic solution to the tyrosine solution so that the pH of the tyrosine solution is 11 or higher.

3. 2. The method for producing tyrosine according to claim 1, wherein the step of obtaining the tyrosine redissolution solution comprises adding a basic solution to the primary tyrosine crystals so that the pH of the mixed solution becomes 11 or more to dissolve the primary tyrosine crystals.

4. 2. The method for producing tyrosine according to claim 1, wherein the step of obtaining secondary tyrosine crystals by simultaneous neutralization and crystallization is carried out at 70 to 80°C.

5. 2. The method for producing tyrosine according to claim 1, further comprising the step of filtering the tyrosine solution to obtain a filtrate before the step of obtaining the primary tyrosine crystals.

6. 6. The method for producing tyrosine according to claim 5, further comprising the step of ultrafiltration of the filtrate.

7. 2. The method for producing tyrosine according to claim 1, wherein the basic solution contains at least one selected from the group consisting of NaOH and KOH.

8. 2. The method for producing tyrosine according to claim 1, wherein the acidic solution contains at least one selected from the group consisting of acetic acid, hydrochloric acid, nitric acid, and sulfuric acid.

9. 2. The method for producing tyrosine according to claim 1, further comprising the step of decolorizing the tyrosine redissolution solution before the step of obtaining the secondary tyrosine crystals.

10. 10. The method for producing tyrosine according to claim 9, wherein the decolorizing step comprises: filtering the redissolved tyrosine solution to obtain a filtrate; and adding activated carbon to the filtrate to decolorize the filtrate, thereby obtaining a decolorized redissolved tyrosine solution.

11. 11. The method for producing tyrosine according to claim 10, wherein the decolorizing step further comprises passing the decolorized redissolved solution through a basic anion exchange resin for further decolorization.

12. 2. The method for producing tyrosine according to claim 1, wherein the tyrosine produced by the method for producing tyrosine is in the form of needle-shaped crystals having a crystal size of 70 microns or more and a water content of 15% or less.

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