Method for producing high-purity arginine

Abstract

The present application relates to a method for producing arginine in which a decoloration step is not performed and an anion exchange step is performed separately and simultaneously with an arginine production step, thereby improving the yield of arginine and significantly reducing the time required for production.

Description

Technical Field

[0001] Cross-references to related applications This application claims the benefit of priority based on Korean Patent Application No. 10-2023-0117455, filed on September 5, 2023, and all contents disclosed in the documents of that corresponding Korean patent application are incorporated herein by reference.

[0002] This application relates to a method for producing high-purity arginine. Background Technology

[0003] This invention relates to a method for producing high-purity arginine for use as an animal feed additive from arginine fermentation broth. Conventional methods for producing arginine include the following steps: separating bacterial cells from the arginine fermentation broth, a cation exchange process, a decolorization process, an anion exchange process, followed by crystallization and separation. The decolorization process involves adding activated carbon to adsorb and separate organic impurities or colored ions contained in the arginine process liquid, thereby improving the purity of the arginine solution and the transmittance of arginine. However, the demand for high transmittance arginine products for use as animal feed additives has been declining recently, and environmental problems related to the disposal of spent activated carbon and wastewater from the decolorization process are becoming increasingly prominent.

[0004] [Primary Technology] (Patent Document 1) US 2003-0124686 A1 Summary of the Invention

[0005] Technical issues The purpose of this application is to provide a method for producing arginine.

[0006] Technical solution This application relates to a method for producing arginine, wherein a decolorization process is not performed, and the anion exchange process is performed separately from and simultaneously with the arginine production process, thereby increasing the yield of arginine and significantly reducing the time required for arginine production.

[0007] On the one hand, it provides a method for producing arginine.

[0008] Arginine can be in the form of arginine crystals or arginine powder.

[0009] Definition of terminology In this application, the term "fermentation product" can refer to the product obtained by enzymatic or metabolic decomposition of organic matter using microorganisms. For example, fermentation products can include the culture product itself obtained by culturing microorganisms in a culture medium, a culture product from which cells (microorganisms or a portion thereof) have been removed, a concentrated product, a dried product, or a lyophilized product from which bacterial cells have been removed. Furthermore, in this case, the term "fermentation broth" can include the entire fermentation product containing arginine produced by microorganisms, or it can be a fermentation product from which impurities have been removed.

[0010] In this application, the term "elution fluid" may refer to a liquid that has passed through a cation exchange resin and / or anion exchange resin.

[0011] In this application, the term "process liquid" can be collectively referred to as any liquid introduced into each step of the production of arginine (e.g., arginine crystals) and / or any liquid obtained after each processing step. For example, process liquids may include fermentation broth, eluent, concentrate, filtrate containing arginine, etc.

[0012] In this application, the term "mother liquor" can refer to the liquid remaining after separating arginine (e.g., arginine crystals) through a concentration-crystallization process of a process liquid containing arginine.

[0013] Fermentation broth containing arginine One approach is to provide a method for producing arginine crystals from a fermentation broth containing arginine.

[0014] The arginine-containing fermentation broth can be obtained by culturing microorganisms that produce arginine. These microorganisms include wild-type microorganisms or microorganisms with natural or artificial genetic modifications. Such microorganisms may contain genetic modifications for target proteins used in arginine production and may be microorganisms in which a particular mechanism is weakened or enhanced due to any reason (e.g., insertion of a foreign gene or enhancement or inactivation of an endogenous gene).

[0015] According to this application, the microorganism producing arginine can be a naturally occurring microorganism capable of producing arginine, or a microorganism whose arginine production capacity is imparted to a microorganism lacking arginine production capacity, but is not limited thereto. Specifically, in this application, the microorganism producing arginine or the microorganism capable of producing arginine can be a microorganism in which a portion of genes in the arginine biosynthesis pathway is enhanced or weakened, or a portion of genes in the arginine degradation pathway is enhanced or weakened. In this application, the term "enhanced" or "increased" arginine production capacity of a microorganism means that the arginine production capacity of the microorganism in this application is improved compared to other microorganisms, parental strains (or mother strains), or unmodified microorganisms other than the microorganisms in this application. For example, compared to the arginine production capacity of other microorganisms, the arginine production capacity of the microorganism in this application can be increased by about 1% or more, 2% or more, 5% or more, 10% or more, 100% or more, 200% or more, 500% or more, 1000% or more, 1100% or more, 1200% or more, or 1300% or more, but is not limited thereto. The term “about” includes, but is not limited to, the range of ±0.5, ±0.4, ±0.3, ±0.2, ±0.1, etc., and includes, but is not limited to, all values ​​in the range that are equivalent to or similar to the numerical values ​​following the term “about”.

[0016] The microorganisms producing arginine can be microorganisms of the genus *Escherichia*, *Bacillus*, *Saccharomyces*, or *Corynebacterium*. If the microorganism is *Escherichia*, it can be *Escherichia coli*. If the microorganism is *Bacillus*, it can be one or more selected from the group consisting of *Bacillus subtilis*, *Bacillus vulgaris*, and *Bacillus cereus*. If the microorganism is *Saccharomyces*, it can be *Saccharomyces cerevisiae*. When the microorganism is a Corynebacterium, it can be one or more selected from the group consisting of: Corynebacterium glutamicum, Corynebacterium erythrogenes, Corynebacterium crudilactis, Corynebacterium deserti, Corynebacterium efficiens, Corynebacterium callunae, Corynebacterium stationis, Corynebacterium singulare, Corynebacterium halotolerans, Corynebacterium striatum, Corynebacterium ammoniagenes, Corynebacterium pollutisoli, and Corynebacterium mimicry. The microorganisms may include, for example, Corynebacterium testudinoris, Corynebacterium crenatum, and Corynebacterium flavescens, but are not limited thereto.

[0017] The cultivation of the microorganisms producing arginine can be carried out according to suitable culture media and cultivation conditions known in the art. Those skilled in the art can easily adjust and use the cultivation method based on the selected strain. Specifically, the cultivation can be batch, continuous, or fed-batch, but is not limited thereto. In this application, the term "culture medium" refers to a substance primarily mixed with the nutrients required for the cultivation of microorganisms, supplying nutrients and growth factors, as well as water necessary for survival and growth. Specifically, the culture medium and other cultivation conditions used to cultivate the microorganisms of this application can be any culture medium used for cultivating general microorganisms, without particular limitation. However, the microorganisms of this application can be cultivated under aerobic conditions in a common culture medium containing suitable carbon sources, nitrogen sources, phosphorus sources, inorganic compounds, amino acids, and / or vitamins, while controlling temperature, pH, etc.

[0018] In one instance, the fermentation broth containing arginine may be a fermentation broth from which cells (e.g., microorganisms that produce arginine, or a portion thereof) have been removed.

[0019] Cells can be removed from the fermentation broth using conventional methods, such as separation (e.g., centrifugation) and filtration (e.g., using cell separation equipment, ceramic membrane filters, etc.).

[0020] Step (a): Passing the fermentation broth containing arginine through a cation exchange resin (cation exchange process). The method for producing arginine according to this application may include the step of passing a fermentation broth containing arginine through a cation exchange resin.

[0021] The cation exchange resin can remove cationic impurities. The cation exchange resin can be a known cation exchange resin, such as a strongly acidic cation exchange resin (SAC) or a weakly acidic cation exchange resin (WAC), but is not limited thereto. The cation exchange resin can be gel-type or porous, but is not limited thereto.

[0022] The cationic impurities may be alkali metal ions (e.g., sodium ions, potassium ions, etc.), alkaline earth metal ions (e.g., magnesium ions, calcium ions, etc.), or ammonium ions, etc.

[0023] The cation exchange process may include a step of treating the eluent to desorb arginine adsorbed onto the cation exchange resin.

[0024] The eluent can be any substance conventionally used to separate substances remaining on the stationary phase without limitation, and in one instance, sodium hydroxide or ammonia solution can be used as the eluent, but is not limited thereto.

[0025] In one example, the eluent can be used at a variety of concentrations, and for example, it can be used at concentrations of 0.01 to 5 N, 0.01 to 4 N, 0.01 to 3 N, 0.01 to 2 N, 0.01 to 1 N, 0.05 to 5 N, 0.05 to 4 N, 0.05 to 3 N, 0.05 to 2 N, 0.05 to 1 N, 0.1 to 5 N, 0.1 to 4 N, 0.1 to 3 N, 0.1 to 2 N, 0.1 to 1 N, 0.5 to 5 N, 0.5 to 4 N, 0.5 to 3 N, 0.5 to 2 N, 0.5 to 1 N, 1 to 5 N, 1 to 4 N, 1 to 3 N, 1 to 2 N, 2 to 5 N, 2 to 4 N, 2 to 3 N, 2.5 to 5 N, 2.5 to 4 N, or 2.5 to 3 N.

[0026] The cation exchange process may include a step of concentrating the eluent under high temperature conditions to remove the used eluent from the eluent obtained from the cation exchange process after the eluent treatment step.

[0027] High-temperature conditions can be set without limitation, as long as the conditions can remove the used eluent (e.g., ammonia solution, etc.), and in one instance, it can be 30°C or higher, 35°C or higher, 40°C or higher, 45°C or higher, 50°C or higher, 55°C or higher, or 60°C or higher.

[0028] The concentration step can be a step of concentrating the eluent to the concentration required to obtain arginine in crystalline form.

[0029] The concentration step may involve concentrating the eluent until the concentration of arginine in the concentrate reaches 100 g / L or less, 110 g / L or less, 120 g / L or less, 130 g / L or less, 140 g / L or less, 150 g / L or less, 160 g / L or less, 170 g / L or less, 180 g / L or less, 190 g / L or less, 200 g / L or less, 210 g / L or less, 220 g / L or less, 230 g / L or less, 240 g / L or less, 250 g / L or less, 30 to 100 g / L, 30 to 110 g / L, 30 to 120 g / L, 30 to 130 g / L, 30 to 140 g / L, 30 to 150 g / L, 30 to 16 ... g / l, 30 to 170 g / l, 30 to 180 g / l, 30 to 190 g / l, 30 to 200 g / l, 30 to 210 g / l, 30 to 230 g / l, 30 to 240 g / l, 30 to 250 g / l, 40 to 100 g / l, 40 to 110 g / l, 40 to 120 g / l, 40 to 130 g / l, 40 to 140 g / l, 40 to 150 g / l, 40 to 160 g / l, 40 to 170 g / l, 40 to 180 g / l, 40 to 190 g / l, 40 to 200 g / l, 40 to 210 g / l, 40 to 220 g / l, 40 to 230 g / l, 40 to 240 g / l, 40 to 250 g / l g / l, 50 to 100 g / l, 50 to 110 g / l, 50 to 120 g / l, 50 to 130 g / l, 50 to 140 g / l, 50 to 150 g / l, 50 to 160 g / l, 50 to 170 g / l, 50 to 180 g / l, 50 to 190 g / l, 50 to 200 g / l, 50 to 210 g / l, 50 to 220 g / l, 50 to 230 g / l, 50 to 240 g / l, 50 to 250 g / l, 60 to 100 g / l, 60 to 110 g / l, 60 to 120 g / l, 60 to 130 g / l, 60 to 140 g / l, 60 to 150 g / l, 60 to 160 g / l, 60 to 170 g / l g / l, 60 to 180 g / l, 60 to 190 g / l, 60 to 200 g / l, 60 to 210 g / l, 60 to 220 g / l, 60 to 230 g / l, 60 to 240 g / l, 60 to 250 g / l, 70 to 100 g / l, 70 to 110 g / l, 70 to 120 g / l, 70 to 130 g / l, 70 to 140 g / l, 70 to 150 g / l, 70 to 160 g / l, 70 to 170 g / l, 70 to 180 g / lThe steps may be 70 to 190 g / l, 70 to 200 g / l, 70 to 210 g / l, 70 to 220 g / l, 70 to 230 g / l, 70 to 240 g / l, or 70 to 250 g / l, but are not limited thereto.

[0030] Step (b): The process liquid obtained in step (a) is concentrated and crystallized (concentration-crystallization process). The method for producing arginine according to this application may include the steps of concentrating and crystallizing the process liquid obtained in step (a) (concentration-crystallization).

[0031] The process liquid obtained in step (a) can be an eluent obtained by passing a fermentation broth containing arginine through a cation exchange process, or a concentrate obtained by concentrating the eluent.

[0032] The concentration-crystallization process can be a step of concentrating arginine to a concentration that yields arginine in crystalline form. The concentration and crystallization processes are carried out such that the concentration of arginine in the concentrate is 200 g / L or higher, 250 g / L or higher, 300 g / L or higher, 350 g / L or higher, 400 g / L or higher, 450 g / L or higher, 500 g / L or higher, 550 g / L or higher, 600 g / L or higher, 650 g / L or higher (upper limit approximately 700 g / L), 200 to 700 g / L, 200 to 650 g / L, 200 to 600 g / L, 200 to 550 g / L, 200 to 500 g / L, 250 to 700 g / L, 250 to 650 g / L, 250 to 600 g / L, 250 to 550 g / L, 250 to 500 g / L, 300 to 700 g / L, 300 to 650 g / L. g / l, 300 to 600 g / l, 300 to 550 g / l, 300 to 500 g / l, 350 to 700 g / l, 350 to 650 g / l, 350 to 600 g / l, 350 to 550 g / l, 350 to 500 g / l, 400 to 700 g / l, 400 to 650 g / l, 400 to 600 g / l, 400 to 550 g / l, 400 to 500 g / l, 450 to 700 g / l, 450 to 650 g / l, 450 to 600 g / l, 450 to 550 g / l, 450 to 500 g / l, 500 to 700 g / l, 500 to 650 g / l, 500 to 600 g / l, or 500 to 550 g / l, but not limited to these.

[0033] The concentration-crystallization process can be carried out at temperatures that allow arginine to be obtained in crystalline form. In one embodiment, the concentration-crystallization process is carried out at the following temperatures: 30 to 80°C, 30 to 75°C, 30 to 70°C, 30 to 65°C, 30 to 60°C, 30 to 55°C, 30 to 50°C, 35 to 80°C, 35 to 75°C, 35 to 70°C, 35 to 65°C, 35 to 60°C, 35 to 55°C, 35 to 50°C, 40 to 80°C, 40 to 75°C, 40 to 70°C. The temperature may be 0°C, 40 to 65°C, 40 to 60°C, 40 to 55°C, 40 to 50°C, 45 to 80°C, 45 to 75°C, 45 to 70°C, 45 to 65°C, 45 to 60°C, 45 to 55°C, 45 to 50°C, 50 to 80°C, 50 to 75°C, 50 to 70°C, 50 to 65°C, 50 to 60°C, or 50 to 55°C, for example, 55°C.

[0034] The concentration-crystallization process may further include a cooling step to reduce the solubility of arginine and increase the yield of arginine crystals. The cooling step involves cooling the arginine concentrate to 40°C or lower, 35°C or lower, 30°C or lower, 25°C or lower, 20°C or lower, 15°C or lower, 10°C or lower, 5°C or lower (lower limit 0°C), 0 to 40°C, 0 to 35°C, 0 to 30°C, 0 to 25°C, 0 to 20°C, 0 to 15°C, 0 to 10°C, 0 to 5°C, 5 to 40°C, 5 to 35°C, 5 to 30°C, 5 to 25°C, etc. 5 to 20°C, 5 to 15°C, 5 to 10°C, 10 to 40°C, 10 to 35°C, 10 to 30°C, 10 to 25°C, 10 to 20°C, 10 to 15°C, 15 to 40°C, 15 to 35°C, 15 to 30°C, 15 to 20°C, 20 to 40°C, 20 to 35°C, 20 to 30°C, 20 to 25°C, 25 to 40°C, 25 to 35°C, or 25 to 30°C, but not limited to these.

[0035] The cooling step can utilize conventional cooling methods, such as using a cooler.

[0036] Arginine can be obtained through the concentration-crystallization process, and the remaining liquid after obtaining arginine can be separated as mother liquor.

[0037] Step (b) may also include drying the obtained arginine, and by removing moisture, high-purity arginine can be finally obtained.

[0038] Arginine can be in the form of arginine crystals or arginine powder.

[0039] Conventional methods for producing arginine include a decolorization process, which raises the issue of handling the waste activated carbon and wastewater generated during decolorization. Furthermore, these conventional methods involve anion exchange processes in arginine production, resulting in a significant time commitment for the process.

[0040] However, in the method for producing arginine disclosed herein, by omitting the decolorization process and performing the anion exchange process separately and simultaneously with the arginine production process, the yield of arginine can be increased and the time required for arginine production can be significantly reduced.

[0041] Therefore, the method for producing arginine in this application is characterized in that the mother liquor separated in the concentration-crystallization step is separated from the arginine production process, passed through an anion exchange resin in a separate process to remove impurities, and the resulting eluent is reused in steps (a), (b), or (a) and (b). These steps will be described in more detail in step (c) below.

[0042] Step (c): Pass the mother liquor obtained in step (b) through anion exchange resin (anion exchange process). The method for producing arginine according to this application may include passing the mother liquor separated in step (b) (concentration-crystallization step) through an anion exchange resin.

[0043] The anion exchange resin can remove anionic impurities. The anion exchange resin can be any known anion exchange resin, such as a strongly basic anion exchange resin (SBA) or a weakly basic anion exchange resin (WBA), but is not limited thereto. The anion exchange resin can be gel-type or porous, but is not limited thereto.

[0044] The anionic impurities may include, but are not limited to, sulfate (SO4) ions. 2- ), phosphate (PO4) 2- ), chloride ions (Cl) - )wait.

[0045] The mother liquor obtained through anion exchange resin can remove anionic impurities, thereby improving the color absorbance of the liquid or the final product arginine.

[0046] Step (c) is characterized by being spatially separate from steps (a) and (b).

[0047] In other words, the anion exchange process in step (c) is characterized by being spatially separate from the cation exchange process in step (a) and the concentration-crystallization process in step (b) (these two processes are the main processes for producing arginine), but occurring simultaneously.

[0048] Although the anion exchange process in step (c) is a time-consuming process, the total time required to produce arginine can be significantly reduced because it is carried out simultaneously with and spatially separately from steps (a) and (b).

[0049] Step (d): The step of reusing the eluent obtained in step (c). Arginine is a highly soluble amino acid, and the mother liquor separated in step (b) also contains a large amount of arginine. Therefore, it is important to effectively reuse the mother liquor. Therefore, the method for producing arginine according to this application may include mixing the eluent obtained by subjecting the mother liquor to anion exchange with the arginine process liquid from steps (a), (b), or (a) and (b), and repeating the process.

[0050] Specifically, the arginine process liquid in step (a) can refer to (i) the fermentation broth containing arginine in step (a), (ii) the eluent obtained by subjecting the fermentation broth containing arginine to a cation exchange process, or (iii) the concentrate obtained by subjecting the eluent to a concentration process.

[0051] The arginine process liquid in step (b) can refer to the liquid to be processed by the concentration-crystallization process in step (b), that is, the eluent obtained by the cation exchange process of the fermentation broth containing arginine in step (a), or the concentrate obtained by the concentration process of the eluent.

[0052] In this way, the mother liquor separated in step (b) is subjected to an anion exchange process as an independent process spatially separate from the arginine production process, and the eluent obtained by the anion exchange process is mixed with the arginine process liquid of step (a) and / or step (b) of the arginine production process, so that the anion exchange process and the arginine production process can be carried out simultaneously, thereby significantly reducing the time required for arginine production.

[0053] In the method for producing arginine in this application, steps (a) to (d) can be repeated.

[0054] In other words, the method for producing arginine in this application includes: (a) The step of passing fermentation broth containing arginine through a cation exchange resin (cation exchange process). (b) The step of concentrating and crystallizing the process liquid obtained in step (a) (concentration-crystallization process); (c) Passing the mother liquor obtained in step (b) through an anion exchange resin (anion exchange process); and (d): The eluent obtained in step (c) may be reused in steps (a), (b), or both (a) and (b). Steps (a) to (d) can be repeated.

[0055] The method for producing arginine in this application is characterized by not performing a decolorization process.

[0056] The method for producing arginine in this application does not show significant differences in the quality (purity, color absorbance, bulk density (BD)) of the final produced arginine, despite the absence of a decolorization process. Therefore, the method eliminates the need for processes such as treating waste activated carbon and wastewater generated during the decolorization process, thus achieving environmentally friendly and economical results. Furthermore, by omitting the decolorization process, the time required for the decolorization process can be reduced.

[0057] In the method for producing arginine in this application, the anion exchange process is performed separately from and simultaneously with the arginine production process, thereby increasing the arginine yield and significantly reducing the time required for arginine production compared to arginine production methods that do not separate the anion exchange process.

[0058] In one instance, compared to methods for producing arginine that include a decolorization process and / or do not involve separate anion exchange processes, the method for producing arginine of this application can increase the arginine yield by 1% or more, 2% or more, or 3% or more, and due to this increase in arginine yield, the amount of raw materials and excipients used in arginine production can be reduced, thereby significantly reducing manufacturing costs.

[0059] In one instance, compared to methods for producing arginine that include a decolorization process and / or do not involve separate anion exchange processes, the method for producing arginine of this application can reduce the time required to produce arginine by 1% or more, 2% or more, 3% or more, 4% or more, 5% or more, 6% or more, 7% or more, 8% or more, 9% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, or 40% or more.

[0060] In one instance, compared to methods for producing arginine that include a decolorization process and / or do not involve a distinct anion exchange process, the method for producing arginine of this application can reduce the time required to produce arginine by about 1 hour or more, 2 hours or more, 3 hours or more, 4 hours or more, 5 hours or more, 6 hours or more, 7 hours or more, 8 hours or more, 9 hours or more, 10 hours or more, 15 hours or more, 20 hours or more, 25 hours or more, or 30 hours or more.

[0061] Beneficial effects This application relates to a method for producing arginine, wherein a decolorization step is omitted and the anion exchange process is performed separately from and simultaneously with the arginine production process, thereby increasing the yield of arginine and significantly reducing the time required for production. Attached Figure Description

[0062] Figure 1 A schematic diagram is shown of a conventional arginine production method including a decolorization process and the arginine production method of this application. Detailed Implementation

[0063] The present invention will now be described in more detail with reference to the following embodiments. However, these embodiments are merely illustrative and the scope of the invention is not limited thereto.

[0064] This application relates to a method for producing arginine, wherein a decolorization step is omitted, and the anion exchange process is performed separately from and simultaneously with the arginine production process, thereby increasing the yield of arginine and significantly reducing the production time required. To verify the effectiveness of this application, the method for producing arginine according to this application is compared with a conventional arginine production method that includes a decolorization process and an anion exchange process as part of the arginine production process, and the following results are shown.

[0065] Comparative Example 1. Conventional methods for producing arginine a) Obtain a fermentation broth containing arginine. To produce high-purity arginine using this method, arginine-producing microorganisms were cultured to obtain a fermentation broth containing arginine (arginine fermentation broth), which has the composition shown in Table 1 below. The arginine fermentation broth contains the cultured microorganisms and culture medium components; the moisture content and composition were analyzed to show them in Table 1 below.

[0066] [Table 1] Composition analysis of arginine fermentation broth The pH of the arginine fermentation solution was adjusted down to 4.0 by treating it with sulfuric acid, and the microbial cells used for arginine fermentation were separated or filtered using cell separation equipment (e.g., membrane filters, mechanical separators, etc.).

[0067] b) Passing the arginine fermentation solution through a cation exchange resin (cation exchange process) The arginine fermentation broth, from which microbial cells have been removed, was passed through a cation exchange resin (MC-08, Samyang Corporation) to obtain an arginine eluent, in which anions were separated by resin-arginine adsorption / elution. The anion separation efficiency during the cation exchange process was approximately 99%. Ammonia (Daejung Chemicals & Metals) was used as the eluent to desorb the arginine adsorbed onto the resin during the cation exchange process.

[0068] c) Steps for removing ammonia and concentrating arginine The arginine eluent obtained in step b) was concentrated (through the liquid of the ion exchange resin) at an internal temperature of 55°C using a vacuum rotary evaporator (BUCHI, Rotavapor R-300) to deammonia, and the arginine concentration was increased from about 72 g / L to 200 g / L.

[0069] d) Pass the concentrate obtained in step c) through an anion exchange resin (anion exchange process). The entire concentrate obtained in step c) is passed through an anion exchange resin (AMP-26, Samyang Corporation) to remove coexisting byproducts by adsorption, thereby recovering the arginine process liquid.

[0070] e) Activated carbon treatment step (decolorization) To improve the permeability of the process liquid through the anion exchange resin, the temperature of the process liquid was raised to 60°C and stirred for approximately 1 hour, while activated carbon at a weight ratio of 3% to arginine was added. The activated carbon was then removed using a Nutsche filter and filter paper to obtain the filtrate.

[0071] f) The step of concentrating and crystallizing the filtrate obtained in step e) to obtain arginine crystals (concentration and crystallization process).

[0072] The filtrate is a process liquid containing high-purity arginine. When the arginine filtrate is concentrated from 200 g / L to approximately 500-550 g / L using a vacuum rotary evaporator at an internal temperature of 50°C, arginine exceeding its solubility precipitates as crystals. After the concentration-crystallization process, the concentrate is cooled to 25-30°C using a cooling circulator to reduce solubility and increase the yield of arginine crystals. The precipitated arginine crystals and mother liquor are separated using a solid-liquid separator (e.g., a basket separator). The separated arginine crystals are then dried in an oven dryer to remove moisture, ultimately yielding high-purity arginine.

[0073] g) The step of reusing the mother liquor obtained in step e). Because arginine is an amino acid with relatively high solubility, a large amount of arginine is retained in the mother liquor generated during arginine crystal separation (i.e., the liquid remaining after arginine crystals have been separated by a concentration-crystallization process using the process liquid containing arginine). Therefore, to improve process recovery, the mother liquor is returned to the arginine eluent from step (b) and / or the arginine process liquid from step (f), and the process is repeated.

[0074] Table 2 below summarizes the physicochemical properties of each process liquid in the conventional arginine production method of Comparative Example 1.

[0075] [Table 2] Comparison of the physicochemical properties of liquids in each process of conventional arginine production methods *Color absorbance: Color value at 430 nm (the lower the value, the clearer the solution).

[0076] *Purity: (weight of arginine / total solid weight in the process liquid) × 100 As shown in Table 2, the anion exchange process is the step that takes the most time of all the processes.

[0077] Example 1. Method for producing arginine without a decolorization process In the conventional arginine production method described in Comparative Example 1, (1) the decolorization process (step e) is not performed, and (2) the anion exchange process (step d) is separated as an independent process and carried out simultaneously with the arginine production process by treating the mother liquor generated in step (f).

[0078] That is, steps a) to c) of Comparative Example 1 are performed in the same manner, but the arginine concentrate obtained in step c) is directly subjected to the concentration-crystallization process in step f) to separate the arginine crystals and the mother liquor.

[0079] Since the anion exchange process is a time-consuming step, in this application, the anion exchange process is separated as an independent process, and the eluent obtained by the anion exchange process of the mother liquor separated in the concentration-crystallization step (i.e., the mother liquor through the anion exchange resin) is mixed with the arginine eluent from step (b) and / or the concentrate fed into the concentration-crystallization process in step (f), and the process is repeated.

[0080] Table 3 below summarizes the mass of the mother liquor obtained during arginine production and the eluent obtained by passing the mother liquor through anion exchange resin.

[0081] [Table 3] *Color absorbance: Color value at 430 nm (the lower the value, the clearer the solution).

[0082] As shown in Table 3 above, compared with the mother liquor, the eluent obtained through anion exchange resin has improved purity and color absorbance.

[0083] The eluent obtained from the anion exchange resin is mixed with the arginine eluent from step (b) (cation exchange process) and the concentrate to be fed into step (f) (concentration-crystallization process), and the process is repeated.

[0084] 3. Comparison of Results When the quality of arginine produced by reusing the mother liquor separated during the arginine production process as in Example 1 through an anion exchange resin without a decolorization process was compared with the quality of arginine produced using a conventional production method (Comparative Example 1), there was no significant difference in the main qualities (purity, pH, BD, etc.) (Table 4 below).

[0085] [Table 4] Comparison of key quality and process indicators However, the method for producing arginine in this application reduces the arginine degradation loss that occurs during the decolorization process by eliminating the decolorization process, thereby increasing the production yield by about 2% and reducing the time required for the decolorization process. Furthermore, by separating the anion exchange process from the arginine production process and performing it simultaneously, the time required for the anion exchange process is reduced, thereby achieving the effect of increasing productivity by reducing the overall process time by about 36%.

[0086] Furthermore, by eliminating the decolorization process, the cost of the decolorization process can be reduced; by eliminating the need to treat waste activated carbon, an environmentally friendly effect can be achieved; and by reducing the amount of raw materials and auxiliary materials, the yield of arginine can be increased, which can significantly reduce manufacturing costs.

[0087] Based on the above description, those skilled in the art will understand that the present invention can be implemented in other specific forms without altering its technical spirit or essential characteristics. In this regard, it should be understood that the above embodiments are illustrative in all respects and not restrictive. The scope of the invention should be interpreted to cover all variations or modifications derived from the meaning and scope of the foregoing claims and their equivalents, rather than the specific embodiments described above.

Claims

1. A method for producing arginine, comprising: (a) The fermentation broth containing arginine is passed through a cation exchange resin to obtain an eluent; (b) The eluent obtained in step (a) is concentrated and crystallized; (c) Pass the mother liquor obtained in step (b) through an anion exchange resin to obtain an eluent; as well as (d) The eluent obtained in step (c) may be reused in steps (a), (b), or steps (a) and (b). Steps (a) to (d) are repeated.

2. The method according to claim 1, wherein the fermentation broth containing arginine is a fermentation product obtained by culturing microorganisms that produce arginine, or a fermentation product from which cells have been removed.

3. The method according to claim 1, wherein step (a) further comprises concentrating the eluent obtained through the cation exchange resin to a concentration of 200 g / L or lower.

4. The method according to claim 1, wherein step (b) is to concentrate arginine to a concentration of 200 g / L or higher.

5. The method according to claim 1, wherein the concentration in step (b) is carried out at 30 to 60°C.

6. The method of claim 1, wherein step (b) further comprises cooling the concentrate to 35°C or lower.

7. The method of claim 1, wherein step (b) further comprises drying the obtained arginine.

8. The method according to claim 1, characterized in that... Step (c) is performed simultaneously with steps (a) and (b).

9. The method according to any one of claims 1 to 8, characterized in that... No decolorization process is performed.

10. The method according to any one of claims 1 to 8, wherein the time required to produce arginine is reduced by 20% or more compared to methods for producing arginine in which anion exchange is not performed separately.

11. The method according to any one of claims 1 to 8, wherein the method for producing arginine is a method for producing arginine crystals or arginine powder.

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