Process for preparing fermentation product

Abstract

The present disclosure relates to a method for producing a fermentation product, comprising: a step of drying a process liquid comprising the fermentation product to obtain the fermentation product, in which the glass transition temperature of the process liquid is calculated on the basis of the (by mass) content of the fermentation product in the process liquid and the glass transition temperature of the fermentation product; the drying process temperature of the process liquid is set on the basis of the glass transition temperature of the process liquid. According to the present disclosure, the optimal drying temperature is set according to the type and amount of the fermentation product to be prepared, so that errors in the drying process can be reduced, and the fermentation product can be efficiently produced.

Description

Technical Field

[0001] The present disclosure relates to a method for producing a fermentation product, which includes a drying process. Background Art

[0002] Fermentation products refer to useful substances produced by microorganisms, fungi, etc. Typical examples of fermentation products are amino acids or nucleic acids.

[0003] For amino acids and nucleic acids, existing crystalline powder and concentrated liquid products are commercially available. In the case of existing crystalline powder products, product yield is limited because it is difficult to completely recover the product from the solvent, and due to the high temperature drying to remove the solvent on the surface of the product, products with low thermal stability may easily deform. In contrast, spray-dried products have high product yields because the solvent in which the solute is dissolved is completely volatilized, and because the particle size of the solvent is small and the time of exposure to heat during the drying process is short, it has advantages in pulverizing substances with poor thermal stability.

[0004] Therefore, research on commercial drying of fermentation products is being conducted in various fields. However, in the case of fermentation products, especially amino acids, drying characteristics are affected by the content and purity of each substance and the type and mixing amount of excipients, and therefore, product quality and product yield are affected depending on the drying conditions; therefore, precise adjustment is necessary.

[0005] In the past, drying process conditions were adjusted empirically. However, as the types of fermentation products have become more diverse and the types of added substances (such as excipients) have also varied greatly, empirically determining process conditions has limitations. In addition, it is not cost-effective to determine process conditions empirically and confirm them through trial and error until the process conditions are established. Summary of the Invention

[0006] [Technical Issues]

[0007] The present disclosure has been designed to implement optimal drying process conditions for efficient production of fermentation products prepared by fermentation processes.

[0008] [Technical solution]

[0009] One object of the present disclosure is to provide a method for efficiently producing a fermentation product prepared by a fermentation process.

[0010] Another object of the present disclosure is to provide a system for implementing optimal drying process conditions for fermentation product production.

[0011] [Beneficial Effects]

[0012] According to the present disclosure, by finding the optimal spray drying conditions for each desired fermentation product based on the spray drying temperature calculation equation of the material information of each desired fermentation product, high-quality fermentation products can be produced at high yields. In particular, even if the thermal stability of the fermentation product is low, the product can be stably produced at high yields by spray drying (wherein the product characteristics are taken into consideration). BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is a flow chart showing a method for producing a fermentation product according to the present disclosure.

[0014] Figure 2 is a cross-sectional view showing a spray drying apparatus according to one aspect of the present invention.

[0015] Figure 3 is a flow chart showing a method for calculating a drying process temperature of a process liquid according to one aspect of the present disclosure.

[0016] Figure 4 is a graph showing the spray drying process yield according to the outlet temperature difference (ΔT) of the spray drying process according to Experimental Example 1.

[0017] Figure 5 is a graph analyzing the relationship between the outlet temperature difference of the spray drying process and the difference (ΔT) between the glass transition temperature of the process liquid calculated according to one aspect of the present disclosure and the yield of the spray drying process. DETAILED DESCRIPTION

[0018] The present disclosure will be described in detail below. At the same time, each description and embodiment disclosed herein can be applied to other descriptions and embodiments respectively. In other words, all combinations of the various elements disclosed herein fall within the scope of the present disclosure. In addition, the scope of the present disclosure is not limited by the specific description described below.

[0019] According to the present disclosure, the glass transition temperature of the process liquid can be calculated based on the mass content of the fermentation product contained in the process liquid and the glass transition temperature of the fermentation product to be produced. Then, the drying process temperature of the process liquid can be determined based on the calculated glass transition temperature of the process liquid. Therefore, the optimal process conditions that can increase the process yield and stably produce the fermentation product into a powder can be implemented without multiple trials and errors.

[0020] Figure 1 is a flow chart showing a method for producing a fermentation product according to the present disclosure.

[0021] Reference Figure 1 , the method for producing a fermentation product according to the present disclosure includes drying a process liquid containing a fermentation product to obtain a fermentation product. Hereinafter, each step will be described in detail.

[0022] Reference Figure 1 In order to produce a fermentation product, a step of preparing a process liquid containing the fermentation product is first performed (S100).

[0023] The fermentation product contained in the process liquid prepared in the step (S100) of preparing the process liquid can be an amino acid or a nucleic acid. When the fermentation product contained in the process liquid is an amino acid, the amino acid can be at least one selected from the group consisting of glycine, alanine, serine, proline, valine, threonine, cysteine, isoleucine, leucine, asparagine, aspartic acid, glutamine, lysine, glutamic acid, methionine, histidine, phenylalanine, selenocysteine, arginine, tyrosine and tryptophan. When the fermentation product is a nucleic acid, the nucleic acid can refer to a compound consisting of a base, a sugar and a phosphate. Specifically, in the present disclosure, the nucleic acid can be any one or more selected from the group consisting of 5'-guanosine monophosphate (5'-GMP) and 5'-inosine monophosphate (5'-IMP). The above-mentioned fermentation products are exemplary, and in addition to the above examples, the present disclosure can also be applied to the production of fermentation products. This is because in the present disclosure, the drying process temperature is calculated based on the glass transition temperature and the content of the fermentation product, and the glass transition temperature is a unique feature of the fermentation product.

[0024] In the step (S100) of preparing the process liquid, a single type of fermentation product or a mixture of multiple types of fermentation products may be provided. If the glass transition temperature of each fermentation product provided in the process liquid and the content of the fermentation product in the process liquid are known, the glass transition temperature of the process liquid can be calculated, and therefore, even when multiple types of fermentation products are mixed, the process temperature can be optimized according to the present disclosure.

[0025] The process liquid in the step (S100) of preparing the process liquid may refer to a fermentation liquid containing the above-mentioned fermentation product. As used herein, "fermentation liquid" may refer to a product produced by enzymatic decomposition or metabolic decomposition of organic matter using microorganisms. For example, the fermentation liquid may include the culture itself obtained by culturing microorganisms in a culture medium, or a concentrate, dried product, or freeze-dried product of the culture obtained by removing a strain therefrom. In addition, in this case, the fermentation liquid may include the entire fermentation liquid containing the fermentation product, or may be a fermentation liquid from which impurities have been removed from the fermentation liquid containing the fermentation product.

[0026] The “microorganism for producing a fermentation product” or “microorganism for producing a fermentation product or a desired product” used in the step (S100) of preparing a process liquid includes all wild-type microorganisms, or naturally or artificially genetically modified microorganisms, and it can be a microorganism in which a specific mechanism is weakened or enhanced due to the insertion of exogenous genes or the enhancement or inactivation of endogenous gene activity, etc., and can be a microorganism that includes genetic modification to produce a desired protein or fermentation product.

[0027] The microorganism for producing the fermentation product of the present disclosure can be a microorganism that naturally has a specific fermentation product production ability, or a microorganism of a parent strain that has been endowed with a fermentation product production ability without a fermentation product production ability, but is not limited thereto. Specifically, as used herein, the microorganism for producing a fermentation product or a desired product, or the microorganism with a fermentation product or a desired product production ability can be a microorganism in which some genes in the biosynthetic pathway of a desired protein or a desired product are enhanced or weakened, or some genes in the degradation pathway of a desired protein or a desired product are enhanced or weakened. The "enhancement" or "increase" of the fermentation product production ability of a microorganism of the present disclosure can mean that the specific fermentation product production ability of a microorganism of the present disclosure is enhanced compared to the fermentation product production ability of a microorganism that is different from the microorganism of the present disclosure, the parent strain or the unmodified microorganism. In one example, compared to the specific fermentation product production capacity of other microorganisms, the microorganisms of the present disclosure can have an enhanced production capacity of about 1% or more, 10% or more, 100% or more, 200% or more, 500% or more, 1000% or more, 1100% or more, 1200% or more, 1300% or more, or about 1.01 times or more, 2 times or more, 5 times or more, 10 times or more, 11 times or more, 12 times or more, or 13 times or more, but not limited thereto. As used herein, the term "about" refers to a range including ±0.5, ±0.4, ±0.3, ±0.2, ±0.1, etc., and it includes all values ​​equivalent to the value immediately following the term "about" or a value within a similar range, but not limited thereto.

[0028] The above-mentioned microorganism used in the step (S100) of preparing the process liquid can be at least one selected from the group consisting of: Candida famata as a yeast, Eremothecium ashbyii and Ashbyagossypii as ascomycetes, Bacillus subtilis as a bacterium, and a microorganism belonging to the genus Corynebacterium.

[0029] When the microorganism used in the step of preparing the process liquid (S100) is a microorganism belonging to the genus Corynebacterium, the microorganism may specifically be Corynebacterium glutamicum, Corynebacterium crudilactis, Corynebacterium deserti, Corynebacterium efficiens, Corynebacterium callunae, Corynebacterium stationis, Corynebacterium singulare, Corynebacterium halotolerans, Corynebacterium striatum, Corynebacterium ammoniagenes, Corynebacterium pollutisoli, Corynebacterium imitans, Corynebacterium testis, or the like. testudinoris), Corynebacterium crenatum or Corynebacterium flavescens, more specifically Corynebacterium glutamicum, but not limited thereto.

[0030] The step of preparing the process liquid (S100) may further include culturing "microorganisms for producing fermentation products". The cultivation of the microorganisms can be carried out under suitable culture media and culture conditions known in the art. Those skilled in the art can easily adjust this culture process for use according to the strain to be selected. Specifically, the culture can be batch culture, continuous culture and / or fed-batch culture, but is not limited thereto. As used herein, the term "culture medium" refers to a mixture of substances containing the nutrients required for culturing the microorganisms as main components, which provides the nutrients and growth factors and water necessary for survival and growth. Specifically, the culture medium and other culture conditions for culturing the microorganisms of the present invention can be any culture medium for conventional culture of microorganisms, without any particular restrictions. However, the microorganisms of the present invention can be cultured under aerobic conditions in conventional culture media containing suitable carbon sources, nitrogen sources, phosphorus sources, inorganic compounds, amino acids and / or vitamins, while adjusting the temperature, pH value, etc.

[0031] The step of preparing the process liquid (S100) may further include providing an excipient in addition to the fermentation product in the fermentation liquid. The excipient may include, for example, a preservative, a wetting agent, a dispersant, a suspending agent, a buffer, a stabilizer, or an isotonic agent, but is not limited thereto. In addition, the excipient may be a non-naturally occurring substance or a naturally occurring substance, but is not limited thereto.

[0032] The excipients mixed in the step (S100) of preparing the process liquid may be excipients that are allowed to be added to food. For example, the excipients may be at least one selected from the group consisting of: cross-linked sodium carboxymethyl cellulose, gum ghatti, persimmon color, licorice extract, formic acid, geranyl formate, citronellyl formate, isoamyl formate, masticatory substances, geraniol, microcrystalline cellulose, cinnamic acid, methyl cinnamate, ethyl cinnamate, cinnamaldehyde, cinnamyl alcohol, sorghum pigment, benzoyl peroxide, hydrogen peroxide, peracetic acid, ammonium persulfate, guar gum, disodium 5′-guanylate, citric acid, manganese citrate, trisodium citrate, sodium ferrous citrate, ferric citrate, ammonium ferric citrate, potassium citrate, calcium citrate, silicon dioxide, Magnesium Glucoside, Calcium Silicate, Silicone, Diatomaceous Earth, Gluconic Acid, Sodium Gluconate, Copper Gluconate, Magnesium Gluconate, Manganese Gluconate, Zinc Gluconate, Ferrous Gluconate, Potassium Gluconate, Calcium Gluconate, Glutaminase, Butyric Acid, Butyrate, Ethyl Butyrate, Isoamyl Butyrate, Neotame, Nisin, Niacin, Nickel, Nicotinamide, Glucanase, Dextran, Sodium Lauryl Sulfate, Lactase, Lactoferrin Concentrate, Lactitol, Lecithin, Rosin, Locust Bean Gum, rutin, linalool, mannitol, maltol, D-maltitol, sodium metasilicate, sodium metaphosphate, potassium metaphosphate, sodium metabisulfite, potassium metabisulfite, sodium methoxide, sulfur dioxide, myristic acid, microfibrillated cellulose, vanillin, kaolin, betaine, bentonite, powdered cellulose, sodium fluoride, biotin, vitamins, glacial acetic acid, DL-malic acid, sodium saccharin, saffron pigment, acid clay, sodium bisulfite, acidic sodium aluminum phosphate, disodium dihydrogen pyrophosphate, calcium dihydrogen pyrophosphate, Magnesium oxide, zinc oxide, calcium oxide, methyl salicylate, ferric oxide, petroleum wax, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sucralose, shellac, steviol glycosides, stearic acid, sodium stearate, food coloring, benzoic acid, sodium benzoate, alginic acid and sodium alginate, inositol, silicon dioxide, chlorine dioxide, carbon dioxide, titanium dioxide, xanthan gum, lactic acid and sodium lactate, gelatin, gellan gum, aspergillus, carnauba wax, carrageenan, karaya gum, beta carotene, sodium carboxymethylcellulose, calcium carboxymethylcellulose, sodium starch glycolate, casein and sodium caseinate, chitosan, chitin, tara gum, tamarind gum, taurine, tannic acid, palmitic acid, ethyl phenylacetate, isobutyl phenylacetate, pectin, pepsin, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hyaluronic acid, and enzyme extract.

[0033] In the step (S100) of preparing the process liquid, the fermentation liquid can be additionally filtered and decolorized. Impurities can be additionally removed by filtering and decolorizing. The filtering and decolorization processes can be carried out by conventional methods and can be omitted if the process needs to be simplified. In the step (S100) of preparing the process liquid, an additional step of removing the strain can be carried out. The removal of the strain can be carried out by various methods, such as filtration, centrifugation, etc. In addition, in the step (S100) of preparing the process liquid, a desalination process can be carried out. A desalination process can be carried out to remove ionic impurities outside the fermentation product to be produced. The desalination process can be carried out by various methods, such as ion exchange resin, continuous chromatography, etc. In addition, in the step (S100) of preparing the process liquid, a concentration process can be additionally carried out. The concentration process can increase the concentration of the fermentation product in the process liquid and can more easily obtain the fermentation product in the subsequent drying process. There is no restriction on carrying out the concentration process, and various methods such as rotary concentrators can be used.

[0034] In the step of preparing the process liquid (S100), the order of the filtration, decolorization, strain removal, and desalination can be changed as needed. The filtration, decolorization, and desalination can be performed after the strain removal, or the strain removal can be performed after the filtration, decolorization, and desalination. By the filtration, decolorization, strain removal, and desalination, impurities other than the fermentation product in the process liquid can be removed, so that the glass transition temperature of the process liquid can be more accurately calculated in the next step.

[0035] Next, for the prepared process liquid, a step of calculating a drying condition of the process liquid and drying the process liquid according to the calculated condition to obtain a fermentation product is performed ( S200 ).

[0036] Drying of the process liquid can be performed by various methods, but spray drying can be used to obtain the fermentation product in powder form.

[0037] Figure 2 The figure shows a cross-sectional view of a spray drying apparatus according to one aspect of the present invention. Spray drying is a method that can simultaneously perform drying and granulation, directly drying solutions, emulsions, and suspensions into powdered or granular products, eliminating processes such as evaporation and grinding. The fermentation product after spray drying can be dispersed into granules, or the fermentation product in a process liquid can be dried into a powder by removing most of the water.

[0038] Spray drying is a method of instantly obtaining a liquid dry product by spraying liquid once in a hot stream, and may include centrifugal spraying using a rotating disk, pressurized spraying using a pressure nozzle, and the like, but is not limited thereto.

[0039] like Figure 2It has been verified that in the spray drying process, the inlet temperature and outlet temperature of the hot air can be set independently. Generally, if spray drying is carried out at a glass transition temperature (melting and flowing temperature) higher than the glass transition temperature of the polymer material, the material melts in the spray drying chamber and the product discharge pipe, producing a viscous state. This will not only clog the pipeline, but also reduce the fluidity of the dried product and reduce the product recovery rate. For this reason, in order to maintain the appropriate temperature of the spray drying process, the glass transition temperature of the product to be sprayed must be measured in advance, and the spray dryer outlet temperature condition must be set to a temperature lower than the glass transition temperature. Therefore, in the present disclosure, the drying condition set to obtain the fermentation product by the drying process liquid can be the outlet temperature of the spray drying process.

[0040] In the case of fermentation products such as amino acids and organic acids, the molecular weight of the substance is less than 1000 mW, which is a small molecule. Furthermore, since the substance is composed of a mixture of salts and other amino acids rather than a single substance, it is difficult to accurately measure or predict the glass transition temperature. Therefore, in the present disclosure, by deriving a correlation equation between the glass transition temperature of each fermentation broth and the molecular weight of a representative substance and applying this equation as a substitute, and setting the spray drying temperature as possible, the spray drying yield is improved.

[0041] When amino acids and nucleic acids produced by fermentation are obtained as crystalline powders, it is difficult to completely recover the product from the solvent using conventional drying methods, thus limiting the product yield. Furthermore, the fermentation product is dried at high temperatures to remove the solvent from its surface, and products with low thermal stability may easily deform during this process. In contrast, spray-dried products have high product yields because the solvent that dissolves the solutes is completely volatilized. They also have advantages in pulverizing substances with poor thermal stability because the solvent particle size is small and the exposure to heat during the drying process is short. However, for some fermentation products, such as fermented amino acids, spray drying characteristics may vary depending on the content and purity of each substance, as well as the type and amount of excipients. Therefore, product quality and product yield are affected by drying conditions, and precise adjustment of drying conditions is necessary to ensure product quality and yield. According to the present disclosure, by finding the optimal spray drying conditions for each desired fermentation product based on the spray drying temperature calculation equation based on the material information of each desired fermentation product, high-quality fermentation products can be produced at high yields. In particular, even if the thermal stability of the fermentation product is low, the product can be stably produced at high yields by spray drying, taking into account the product characteristics.

[0042] In the above, the method of obtaining a fermentation product from a process liquid containing a fermentation product according to one aspect of the present disclosure is examined. Hereinafter, a method for calculating a drying process condition for a process liquid containing a specific fermentation product will be described.

[0043] Figure 3 is a flow chart illustrating a method for calculating a drying process temperature of a process liquid according to one aspect of the present disclosure.

[0044] Reference Figure 3 , calculating a drying process temperature of the process liquid by calculating the glass transition temperature of the process liquid based on the fermentation product content based on the mass meter in the process liquid and the glass transition temperature of the fermentation product (S210), and setting a process temperature for drying the process liquid based on the glass transition temperature of the process liquid (S220).

[0045] First, in the step ( S210 ) of calculating the glass transition temperature of the process liquid based on the fermentation product content on a mass basis in the process liquid and the glass transition temperature of the fermentation product, the glass transition temperature of the process liquid is calculated according to Equation 1 below.

[0046] [Equation 1]

[0047]

[0048] (In Equation 1 above, T g,SD进料 is the glass transition temperature of the process liquid to which the excipients are mixed, w 发酵液 is the fermentation product content in the process liquid mixed with excipients based on mass, T g,发酵液 is the glass transition temperature of the process liquid, and w 赋形剂 is the mass-based excipient content in the process liquid to which the excipient is mixed, T g,赋形剂 is the glass transition temperature of the excipient).

[0049] If the excipient is not mixed in the process liquid, then w in Equation 1 above is 赋形剂 The value becomes 0. In addition, when multiple fermentation products are provided in the process liquid, multiple sets of w are provided in Equation 1. 发酵液 and T g,发酵液 .

[0050] To determine the fermentation product content on a mass basis contained in the process liquid in Equation 1 above, a sample of the process liquid may be collected, and a chromatographic analysis or the like may be performed on the sample.

[0051] At the same time, the glass transition temperature (T g,发酵液 ) can be calculated from the molecular weight of the fermentation product. The inventors of the present disclosure used the molecular weights of amino acids and nucleic acids and the actual measured glass transition temperature values ​​known from the literature to derive a correlation between the molecular weight and the glass transition temperature of the fermentation product (Equation 2).

[0052] [Equation 2]

[0053] T g,发酵液 (K)=0.0996*MW 工艺液体中的主要发酵产物 328.47

[0054] (In Equation 2 above, MW 工艺液体中的主要发酵产物 is the molecular weight of the main fermentation product contained in the process liquid.)

[0055] Next, a process temperature for drying the process liquid is set based on the glass transition temperature of the process liquid ( S220 ).

[0056] The drying process temperature can be set to 20°C to 25°C higher than the glass transition temperature of the process liquid. Furthermore, the drying process temperature can specifically refer to the outlet temperature of the spray drying process. By setting the drying process temperature to be higher than the glass transition temperature of the process liquid, the yield of the drying process can be increased, and deformation of the fermentation product due to high temperature can be prevented.

[0057] In the above, a method for calculating the drying process temperature of a process liquid according to one aspect of the present disclosure was examined. The method for calculating the drying process temperature for drying can be implemented in the form of a simulation system for a fermentation product production process. The simulation system for a fermentation product production process can be implemented using hardware components, software components, or a combination of hardware and software components to improve the quality and yield of the fermentation product by calculating optimal drying conditions based on the type and content of the fermentation product and the type and content of the excipients. For example, the hardware components may include a microphone, an amplifier, a bandpass filter, an audio-to-digital converter, and a processing device. The processing device can be implemented using one or more general-purpose or special-purpose computers, such as a processor, a controller and an arithmetic logic unit, a digital signal processor, a microcomputer, a field programmable array, a programmable logic unit, a microprocessor, or any other device capable of responding to and executing instructions in a defined manner. The processing device can run an operating system (OS) and one or more software applications running on the OS. The processing device can also access, store, manipulate, process, and create data in response to the execution of the software. For simplicity, the description of the processing device is used in the singular; however, those skilled in the art will understand that the processing device can include multiple processing elements and multiple types of processing elements. For example, the processing means may include multiple processors or a processor and a controller. In addition, different processing configurations are possible, such as parallel processors.

[0058] In addition, the above-mentioned method for calculating the drying process temperature of the process liquid can be implemented in the form of software. The software may include a computer program, a section of code, an instruction or some combination thereof to indicate or configure the processing device to operate as desired independently or collectively. The software and data can be permanently or temporarily installed in any type of machine, component, physical or virtual device, computer storage medium or device, or installed in a propagation signal wave that can provide instructions or data to the processing device or be interpreted by the processing device. The software can also be distributed on a network-coupled computer system, so as to store and execute the software in a distributed manner. The software and data can be stored by one or more non-transitory computer-readable recording media. The method according to the above-mentioned embodiment can be recorded in a non-transitory computer-readable medium including program instructions to implement various operations implemented by the computer. The medium can also include data files, data structures, etc. that are separate or combined with program instructions. The program instructions recorded on the medium can be program instructions specially designed and constructed for the purpose of implementing the embodiment, or they can be types that are well known and available to those skilled in the art of computer software. Examples of non-transitory computer-readable media include magnetic media, such as hard disks, floppy disks, and magnetic tapes; optical media, such as CD ROMs and DVDs; magneto-optical media, such as optical disks; and hardware devices specially configured to store and execute program instructions, such as read-only memory (ROM), random access memory (RAM), flash memory, etc. Examples of program instructions include machine code, such as produced by a compiler, and files containing higher-level code that can be executed by a computer using an interpreter.

[0059] [Modes for Carrying Out the Invention]

[0060] Hereinafter, the present disclosure will be described in detail by way of examples. However, these examples are preferred embodiments provided for illustrative purposes only, and therefore, the scope of the present disclosure is not intended to be limited to or by these examples. Furthermore, those skilled in the art can fully understand and easily implement technical features not described herein in the technical field of the present disclosure or similar technical fields.

[0061] In the above, the fermentation product production process and the simulation system for the fermentation product production process according to one aspect of the present disclosure are examined. Hereinafter, the beneficial effects mentioned in the present disclosure will be described through the experimental results of Examples and Comparative Examples.

[0062] Experimental Example 1. Confirmation of the glass transition temperature calculated from the molecular weight of the fermentation product and the glass transition temperature determined by actual measurement The difference between the glass transition temperatures

[0063] As mentioned above, according to the present invention, the glass transition temperature (T g,发酵液) can be calculated from the molecular weight of the fermentation product. The inventors of the present disclosure used the molecular weights of amino acids and nucleic acids and the actual measured glass transition temperature values ​​known from the literature to derive a correlation between the molecular weight and the glass transition temperature of the fermentation product (Equation 2).

[0064] [Equation 2]

[0065] T g,发酵液 (K)=0.0996*MW 工艺液体中的主要发酵产物 +328.47

[0066] (In Equation 2 above, MW 工艺液体中的主要发酵产物 is the molecular weight of the main fermentation product contained in the process liquid.)

[0067] In Experimental Example 1, the error between the glass transition temperature calculated according to Equation 2 and the glass transition temperature of the fermentation product confirmed by actual measurement was determined, and it was confirmed whether the glass transition temperature calculated according to Equation 2 was reliable.

[0068] Refer to Table 1, T g,发酵液 The difference between the actual value and the calculated value is expressed as an error, and when the correlation coefficient R2 used to determine the accuracy of the model was calculated, it was found that R2 was 0.9831. This is a value that meets the generally accepted standard for determining the validity of correlation coefficients (about 0.95 for biology, about 0.7 for engineering, and about 0.3 for social sciences), which means that the glass transition temperature value calculated according to Equation 2 is a reliable value.

[0069] [Table 1]

[0070]

[0071] Experimental Example 2. Calculation of the glass transition temperature of a process liquid containing glutamic acid and the glass transition temperature based on the calculation. Variable temperature drying process design

[0072] The amino acid fermentation broth with a glutamic acid concentration of 5 wt% and a solid content of 10 wt% in the liquid phase was subjected to a membrane separation process to remove bacterial cells and concentrated to a concentration range of 15 wt% to 30 wt% using a rotary concentrator. The resulting concentrate was decolorized and filtered and mixed with an excipient (maltodextrin (DE20) T g,赋形剂 : 141° C.) to prepare a spray drying process liquid having a glutamic acid content of 15 wt %, an excipient content of 16.7 wt % and a solid content of 40 wt %.

[0073] The spray drying outlet temperature of the process liquid is calculated using equations 1 and 2 identified above. The terms used in the equations are as follows: 发酵液 :0.833,w 赋形剂 :0.167,MW工艺液体中的主要发酵产物 :147.10, and T g,发酵液 : 414.15 K. Using the above values, the spray drying outlet temperature was calculated to obtain a value of 80.07° C., and when spray drying was carried out under these conditions, the product recovery was approximately 80%.

[0074] Experimental Example 3. Analysis of the difference between the calculated glass transition temperature and the spray drying process outlet temperature Process yield

[0075] In Experimental Example 3, the glass transition temperature was calculated for a process liquid of a specific composition, and when the difference between the calculated glass transition temperature and the spray drying process outlet temperature was changed, a change in process yield according to the temperature difference was confirmed.

[0076] In Experimental Example 3, the process yield was calculated as the mass of product obtained relative to the amount of solids in the spray drying process liquid.

[0077] [Spray drying process yield (%) = amount of spray-dried product obtained (wt) / (total amount of spray drying process liquid (wt) * solid content (wt%)) * 100%]

[0078] [Table 2]

[0079]

[0080] Figure 4 3 is a graph showing the spray drying process yield according to the outlet temperature difference (ΔT) of the spray drying process of Experimental Example 3.

[0081] Reference Figure 4 , when the outlet temperature difference (ΔT) of the spray drying process was varied for the process liquid of the same composition, it was confirmed that the process yield was high when the temperature difference was about 20° C. to about 25° C.

[0082] Experimental Example 4. Glass transition temperature calculated for process liquids with different types and contents of excipients. Analysis of process yield by the difference between temperature and outlet temperature of spray drying process

[0083] In Experimental Example 4, the effect of the difference between the glass transition temperature of the process liquid containing the fermentation product calculated by the above method and the outlet temperature of the spray drying process on the yield of the spray drying process was analyzed.

[0084] Table 3 shows the spray drying process yield calculated based on the calculated glass transition temperature (Tg), the type of excipients contained in the process liquid containing glutamic acid as a fermentation product, and the difference (ΔT) between the calculated glass transition temperature and the outlet temperature of the spray drying process. The spray drying process yield was calculated in the same manner as in Experimental Example 3.

[0085] Figure 5Graph analyzing the relationship between the outlet temperature difference of the spray drying process and the difference (ΔT) between the glass transition temperature of the process liquid calculated according to one aspect of the present disclosure and the yield of the spray drying process.

[0086] Table 3 shows the results of spray drying experiments using the same glutamic acid fermentation broth with different types and amounts of excipients.

[0087] [Table 3]

[0088]

[0089] As shown in Table 3 and Figure 5 As demonstrated in the results, regardless of the type and content of the excipients, the average yield of the spray drying process was high when ΔT was between 20°C and 25°C. In contrast, when ΔT was less than 20°C, the average yield of the spray drying process was significantly reduced. Therefore, it was demonstrated that the yield of the spray drying process can be greatly improved by calculating the glass transition temperature of the process liquid and setting the spray drying process outlet temperature based on this temperature.

[0090] Based on the foregoing, those skilled in the art to which the present disclosure pertains will appreciate that the present disclosure may be implemented in other specific forms without modifying the technical concepts or essential features of the present disclosure. In this regard, the exemplary embodiments disclosed herein are for illustrative purposes only and should not be construed as limiting the scope of the present disclosure. On the contrary, the present disclosure is intended to encompass not only the exemplary embodiments, but also various alternatives, modifications, equivalents, and other embodiments that may be included within the spirit and scope of the present disclosure as defined by the appended claims.

Claims

1. A method for producing a fermentation product, comprising: drying the process liquid comprising the fermentation product to obtain the fermentation product, The drying of the process liquid is performed by calculating the glass transition temperature of the process liquid based on the fermentation product content based on mass and the glass transition temperature of the fermentation product in the process liquid, and the drying process temperature of the process liquid is set based on the glass transition temperature of the process liquid. 2 . The method according to claim 1 , wherein the drying of the process liquid is performed by spray drying, and the drying process temperature of the process liquid is the outlet temperature of the spray drying process. The method according to claim 1 , wherein the fermentation product comprises at least one selected from the group consisting of amino acids and nucleic acids.

4. The method according to claim 1, wherein the process liquid further contains an excipient, and in order to calculate the glass transition temperature of the excipient-mixed process liquid containing the excipient, the excipient content on a mass basis in the excipient-mixed process liquid and the glass transition temperature of the excipient are also taken into account.

5. The method of claim 4, wherein the glass transition temperature of the process liquid is calculated using the following equation 1 [Equation 1] (In Equation 1 above, T g,SD进料 is the glass transition temperature of the process liquid to which the excipients are mixed, w 发酵液 is the fermentation product content in the process liquid mixed with excipients based on mass, T g,发酵液 is the glass transition temperature of the process liquid, and w 赋形剂 is the mass-based excipient content in the process liquid to which the excipient is mixed, T g,赋形剂 is the glass transition temperature of the excipient).

6. The method according to claim 5, wherein the glass transition temperature (T g,发 The fermentation liquid) was calculated using the following equation 2 [Equation 2] T g,发酵液 (K)=0.0996*MW 工艺液体中的主要发酵产物 +328.47 (In Equation 2 above, MW 工艺液体中的主要发酵产物 is the molecular weight of the main fermentation product contained in the process liquid). The method according to claim 1 , wherein a process temperature of the drying process is set to be 20° C. to 25° C. higher than a glass transition temperature of a process liquid.

8. The method of claim 1, further comprising removing bacteria from the process liquid and concentrating the process liquid before drying the process liquid.

9. A simulation system for a fermentation product production process, which calculates the glass transition temperature of a process liquid based on the fermentation product content in the process liquid based on a mass meter and the glass transition temperature of the fermentation product, and determines a drying process temperature of the process liquid based on the glass transition temperature of the process liquid to obtain a fermentation product by drying the process liquid containing the fermentation product.

10. A recording medium having recorded thereon software for calculating the glass transition temperature of a process liquid based on the fermentation product content in the process liquid on a mass basis and the glass transition temperature of the fermentation product, and determining a drying process temperature of the process liquid based on the glass transition temperature of the process liquid to obtain a fermentation product by drying the process liquid containing the fermentation product.

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