Composition for improving d-serine productivity

Abstract

To suitably improve D-serine productivity.SOLUTION: A composition for improving D-serine productivity contains sialic acid and sugar.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving D-serine productivity. [Background technology]

[0002] The human intestine is home to 1,000 species and 40 trillion bacteria, forming a complex symbiotic relationship known as the intestinal microbiota. The intestinal bacteria that make up the intestinal microbiota contribute to the maintenance and promotion of human health by producing a variety of metabolic products. In particular, D-serine, a type of D-amino acid, has been reported to play a role in defense against pathogenic bacteria in the intestinal tract and to protect kidney function (Non-Patent Documents 1 and 2). Furthermore, D-serine has been reported to be involved in the control of psychiatric disorders through its return to the brain (Non-Patent Document 3).

[0003] D-serine-producing bacteria with remarkable D-serine productivity have been reported, including Phocaeicola dorei and Phocaeicola vulgatus, and Bacteroides uniformis, both of which belong to the Phocaeicola genus. However, these bacterial species are highly sensitive to oxygen, making them difficult to distribute as live bacterial preparations like lactic acid bacteria and bifidobacteria. Furthermore, there is a lack of experience in human consumption. Therefore, there is a need to find a composition that can improve the D-serine productivity of D-serine-producing bacteria normally present in the human intestine. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] ISME J.2015 Mar;9(4):1052. [Non-patent document 2] kidney360.2021 Aug:2(10):1611-1624. [Non-patent document 3] FEBS J.2008 Jul:275(14):3514-3526. Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to preferably improve the D-serine productivity of D-serine-producing bacteria. [Means for solving the problem]

[0006] A composition for improving D-serine productivity according to embodiment 1 comprises sialic acid and a sugar. A second aspect is the composition for improving D-serine productivity according to the first aspect, wherein the sugar is galacto-N-biose.

[0007] Aspect 3 is the composition for improving D-serine productivity according to Aspect 1, wherein the sugar is lactose. A fourth aspect is the composition for improving D-serine productivity according to the first aspect, wherein the sugar is galactose.

[0008] Aspect 5 is the composition for improving D-serine productivity of Aspect 2, which is used to improve D-serine productivity by a D-serine-producing bacterium, wherein the D-serine-producing bacterium is at least one species selected from the group consisting of Focaecola dorei, Focaecola vulgatus, and Bacteroides uniformis.

[0009] A sixth aspect is the composition for improving D-serine productivity according to the third or fourth aspect, which is used to improve D-serine productivity by a D-serine-producing bacterium, wherein the D-serine-producing bacterium is at least one species selected from the group consisting of Focaecola vulgatus and Bacteroides uniformis. [Effects of the Invention]

[0010] The composition for improving D-serine productivity of the present invention can suitably improve the D-serine productivity of D-serine-producing bacteria. DETAILED DESCRIPTION OF THE INVENTION

[0011] A specific embodiment of the composition for improving D-serine productivity according to the present invention will be described below. The composition for improving D-serine productivity contains sialic acid and a sugar. The above components contained in the composition for improving D-serine productivity will be described below.

[0012] <Sialic acid> Sialic acid is a negatively charged nine-carbon sugar and is a general term for modified neuraminic acid having an amino group and a carboxy group. Sialic acid also includes substances in which the amino group or hydroxy group of neuraminic acid is substituted. Specific examples of sialic acid include N-acetylneuraminic acid (NeuAc), N-glycolylneuraminic acid (NeuGc), and deaminoneuraminic acid (KDN). Among these, N-acetylneuraminic acid is a major sialic acid found in various biological species. In vivo, sialic acid exists in a free state as well as in the molecular forms of oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Specific examples of glycopeptides include N-acetylneuraminic acid-linked glycopeptides. It is preferable that the sialic acid contains at least one of N-acetylneuraminic acid and N-acetylneuraminic acid-linked glycopeptides.

[0013] The content of sialic acid in the composition for promoting the growth of D-serine-producing bacteria is preferably, for example, 0.5 mmol / g or more and less than 1 mmol / g. <sugar> The sugar is not particularly limited, and can be a monosaccharide, a disaccharide, an oligosaccharide, etc. The oligosaccharide means a saccharide oligomer in which several monosaccharides are linked together by glycosidic bonds.

[0014] Specific examples of the sugar include, for example, galacto-N-biose, lactose, galactose, sialyllactose, sialylgalactose, etc. Galacto-N-biose is a disaccharide in which galactose and N-acetylgalactosamine are β1-3 linked. Among these, the sugar is preferably at least one selected from galacto-N-biose, lactose, and galactose. Note that the above sugar does not contain sialic acid. Also, the above sialyllactose and sialylgalactose are assumed to contain both sialic acid and sugar.

[0015] <Casein-derived peptide> The composition for improving D-serine productivity may contain a casein-derived peptide in addition to the above sialic acid and sugar.

[0016] Casein is a kind of milk protein contained in dairy products. Milk protein is roughly classified into whey, also called whey, and casein. Casein-derived peptides are produced by acid hydrolysis of casein, protease treatment, fermentation by microorganisms, etc. Among these, casein-derived peptides are preferably degradation products produced by protease treatment.

[0017] Specific examples of casein-derived peptides include, for example, casamino acids, tryptone, etc. The nitrogen content of the casein-derived peptide in the composition for improving D-serine productivity is not particularly limited, but is preferably, for example, 8% by mass or more and 16% by mass or less.

[0018] <Composition for improving D-serine productivity> The composition for improving D-serine productivity may be a mixture of the above sialic acid and sugar, or a compound formed by the binding of sialic acid and sugar.

[0019] Further, the composition for improving D-serine productivity may be a mixture of the above sialic acid, sugar, and casein-derived peptide, or may be a compound formed by the binding of sialic acid, sugar, and casein-derived peptide.

[0020] <D-serine-producing bacterium> Examples of D-serine-producing bacteria include bacteria belonging to the genera Collinsella, Bacteroides, Phocaeicola, Parabacteroides, Blautia, Dorea, Ruminococcus, Roseburia, Agathobacter, Streptococcus, Clostridium, Flavonifractor, Coprococcus, and Faecalibacterium. Here, for intestinal bacterial species, it refers to bacterial species with a homology of 97% or more, more preferably 98% or more, and even more preferably 99% or more in the nucleotide sequence of the 16S ribosomal RNA gene with each reference strain.

[0021] In the composition for improving D-serine productivity, the D-serine-producing bacterium may be the cells of one bacterial species among the bacterial species included in each of the above genera, or may be a combination of the cells of two or more bacterial species.

[0022] The D-serine-producing bacterium is preferably at least one selected from Phocaeicola dorei, Phocaeicola vulgatus, and Bacteroides uniformis.

[0023] The bacterial culture refers to a culture of bacteria in a medium such as a known preparation, food or drink, feed, or food-grade material. The culture may be a product of further processing, such as concentration, drying, or freeze-drying, of the cultured bacterial cells. The culture may be a suspension containing the cultured bacterial cells and the medium, or may be a supernatant of the culture.

[0024] The term "composition for improving D-serine productivity" refers to a composition that can improve the D-serine productivity of D-serine-producing bacteria. "Improved D-serine productivity" refers to a case where the D-serine concentration after culturing each D-serine-producing bacterium with the addition of the composition minus the D-serine concentration after culturing each D-serine-producing bacterium without the addition of the composition is +0.2 μM or more.

[0025] The composition for improving D-serine productivity refers to a composition in which the difference in D-serine concentration is +0.2 μM or more. In this embodiment, the term "composition" includes preparations, foods and drinks, feeds, and other substances that can be ingested by animals (including humans).

[0026] The method for culturing the D-serine-producing bacteria will now be described. <Culture method> The D-serine-producing bacteria can be cultured using media generally used for culturing enterobacteria. Examples of media generally used for culturing enterobacteria include YCFA medium (JCM medium number 1130), EG medium (JCM medium number 14), GAM bouillon, modified GAM bouillon, etc. The medium may be a liquid medium, a solid medium, or a semi-solid medium.

[0027] The culture temperature is not particularly limited, but may be 36 to 38°C, which is a temperature close to human body temperature, and 37°C is preferred. The large intestine is in an anaerobic state, and the intestinal bacteria that grow here are obligate anaerobes. Therefore, it is necessary to maintain an anaerobic state in the medium and the headspace of the medium with nitrogen gas. In addition, since carbon dioxide and hydrogen gas produced by intestinal bacteria also exist in the intestine, it is preferable to include them. Examples of the ratio include nitrogen 80 - 90%, carbon dioxide 5 - 10%, and hydrogen gas 5 - 10%.

[0028] The culture time is not particularly limited, but it is preferably carried out until the turbidity can be visually confirmed. Various D-serine-producing bacteria are added to about 1.0E+05 cfu / mL with respect to 10 mL of the medium. Further, when adding a composition for improving D-serine productivity, it is added so that the sialic acid content is 0.5 mmol / g or more.

[0029] Hereinafter, the method for measuring the D-serine concentration will be described. <Method for Measuring D-Serine Concentration> The method for measuring the D-serine concentration is not particularly limited, and a known measurement method can be adopted. Examples of known measurement methods include measurement by high performance liquid chromatography (hereinafter also referred to as HPLC), ultra-high performance liquid chromatography (hereinafter also referred to as UHPLC), etc.

[0030] <Other Components> The composition for improving D-serine productivity may contain other components as long as the effects of the composition for improving D-serine productivity are not impaired. Examples of other components include excipients, binders, disintegrants, lubricants, flavoring agents, suspending agents, coating agents, etc. Also, it is possible to make tablets such as tablets, capsules, granules, powders, powders, syrups, etc.

[0031] Hereinafter, the application forms of the composition for improving D-serine productivity will be described. <Application Forms> The application form of the composition for improving D-serine productivity is not particularly limited, and it may be applied as, for example, a feed composition for improving D-serine productivity (hereinafter also referred to as a feed composition), a pharmaceutical composition for improving D-serine productivity (hereinafter also referred to as a pharmaceutical composition), or a food composition for improving D-serine productivity (hereinafter also referred to as a food composition). Pharmaceutical compositions include quasi-drug compositions.

[0032] Hereinafter, uses of the composition for improving D-serine productivity will be described. <Application> The use of the composition for improving D-serine productivity is not particularly limited, and the composition may be incorporated into feed or food or drink, or may be added to raw materials during the production process of feed or food or drink.

[0033] Specific examples of foods and beverages include, but are not limited to, dairy products such as cheese, fermented milk, dairy lactic acid bacteria drinks, lactic acid bacteria drinks, butter, margarine, etc. Other examples include beverages such as milk drinks, fruit juice drinks, and soft drinks, processed egg products such as jelly, candy, pudding, and mayonnaise, and sweets and breads such as butter cake. Further examples include various types of powdered milk, infant foods, nutritional compositions, etc.

[0034] The classification of the above-mentioned food and drink is not particularly limited, and it can be used as a general food, a health functional food, a food for special uses, etc. Furthermore, as a health functional food, it can be used as a food for specified health uses, a food with nutrient function claims, a food with functional claims, etc.

[0035] When indicating the uses of the composition for improving D-serine productivity, examples include indications stipulated by various laws, enforcement regulations, guidelines, etc. Indications of uses include indications on packaging such as wrapping and containers, as well as indications on advertising media such as pamphlets.

[0036] The subject of administration of the composition for improving D-serine productivity is not particularly limited, and it can be administered to humans. The subject of administration may also be animals other than humans (e.g., dogs, cats, horses, rabbits, etc.). When the subject of administration is humans, it can be administered to, for example, minors under 20 years of age, adults, or elderly people 65 years of age or older.

[0037] <Action and effect> The operation and effects of this embodiment will be described. (1) A composition for improving D-serine productivity contains sialic acid and a sugar. By containing these components, the D-serine productivity of D-serine-producing bacteria can be suitably improved. Therefore, the D-serine concentration can be suitably increased. Furthermore, by suitably improving the D-serine productivity of D-serine-producing bacteria, it can contribute to maintaining good health.

[0038] (2) The sugar is at least one selected from galacto-N-biose, lactose, and galactose, which can more suitably improve the D-serine productivity of the D-serine-producing bacterium.

[0039] (3) The composition for improving D-serine productivity is used to improve D-serine productivity by D-serine-producing bacteria. When the sugar is galacto-N-biose, the D-serine-producing bacteria is preferably at least one selected from the group consisting of Focaecola dorei, Focaecola vulgatus, and Bacteroides uniformis. This allows for more optimal improvement of D-serine productivity by these D-serine-producing bacteria.

[0040] (4) The composition for improving D-serine productivity is used to improve D-serine productivity by D-serine-producing bacteria. When the sugar is lactose or galactose, the D-serine-producing bacteria is preferably at least one selected from Focaulacola vulgatus and Bacteroides uniformis. This allows for more optimal improvement of D-serine productivity by these D-serine-producing bacteria.

[0041] <Example of change> This embodiment can be modified as follows: This embodiment and the following modifications can be combined and implemented within the scope of technical compatibility.

[0042] In this embodiment, the composition for improving D-serine productivity does not contain lactic acid bacteria or bifidobacteria, but is not limited to this embodiment. The composition for improving D-serine productivity may contain lactic acid bacteria or bifidobacteria. [Example]

[0043] Examples will be given below to more specifically illustrate the configuration and effects of the present invention, but the present invention is not limited to these examples. Unless otherwise specified, % indicates % by volume.

[0044] <Test Example 1> 1. Selection of D-serine-producing bacteria and preparation of freeze-concentrated cells (1) Obtaining D-serine-producing bacteria Among the D-serine-producing bacteria, six species corresponding to Phocaicola vulgatus and Bacteroides uniformis were obtained from the Microbial Materials Development Division of the RIKEN BioResource Research Center (hereinafter also referred to as JCM) or the Leibniz Institute for Microbiology and Materials Science (hereinafter also referred to as DSMZ) in Germany.

[0045] (2) Preparation of frozen concentrated bacterial cells The above six bacterial species were cultured in a modified GAM bouillon medium (product code 05433, Nissui). The composition of the modified GAM bouillon medium used is shown in Table 1.

[0046] [Table 1] The modified GAM broth medium was sterilized by heat treatment at 115°C for 15 minutes. The six D-serine-producing bacterial species were inoculated into individual sterilized media and anaerobically cultured at 37°C using an anaerobic workstation (Concept 400, Central Scientific Trading Co., Ltd.). The anaerobic workstation operation was performed by aerating with a mixed gas. The anaerobic gas ratios were 80% (v / v) nitrogen, 10% (v / v) carbon dioxide, and 10% (v / v) hydrogen. Each culture was concentrated by centrifugation, and glycerol was added to a concentration of 10% (v / v) to obtain various concentrated bacterial cells. The concentrated bacterial cells were then frozen at -80°C.

[0047] The frozen concentrated bacterial cells were then thawed, serially diluted, and plated on modified GAM broth agar medium to measure the viable bacterial count. All strains were confirmed to contain a viable bacterial count of 1.0E+07 cfu / mL or more.

[0048] (3) Preparation of a composition for improving D-serine productivity Compositions containing compounds formed by the binding of sialic acid, sugar, and casein-derived peptides were prepared in Examples 1 to 6 and 13 to 18. Specifically, compositions containing sialylgalacto-N-biose were prepared.

[0049] Compositions containing sialyllactose in which sialic acid and sugar are bound were prepared in Examples 7 to 12. 3'-sialyllactose was used as the sialyllactose. As Comparative Examples 1 to 12, compositions containing sialic acid but not containing sugar or casein-derived peptide were prepared.

[0050] Sialic acid and 3'-sialyllactose were commercially available reagents (purity 99.9% or higher). A composition containing sialylgalacto-N-biose was prepared as follows. After adjusting the pH of glycomacropeptide derived from milk casein, it was treated with protease and concentrated using an UF membrane to obtain a retentate. The obtained retentate was then diafiltered against water to obtain another retentate. The obtained retentate was lyophilized to obtain a composition mainly composed of sialylgalacto-N-biose. The composition of the obtained composition is shown in Table 2.

[0051] [Table 2] (4) Cultivation of each D-serine-producing bacterium The above-mentioned frozen concentrated bacterial cells were thawed in an anaerobic workstation, inoculated into 10 mL of modified GAM bouillon medium at a concentration of 1%, and cultured at 37°C for 16 hours in an incubator attached to the workstation.

[0052] The proportions of anaerobic gas aerated were 80% (v / v) nitrogen, 10% (v / v) carbon dioxide, and 10% (v / v) hydrogen. After cultivation, the cells were collected by centrifugation. Chromosomal DNA was then extracted using the DNeasy Blood & Tissue Kit (QIAGEN). The nucleotide sequence of the 16S rRNA gene was determined to confirm that the target bacterial species had been cultivated. Each composition for improving D-serine productivity was added so that the sialic acid content was 0.5 mmol / g equivalent. The turbidity after cultivation was measured at a wavelength of 660 nm. The growth promotion rate was calculated as the ratio of the turbidity after cultivation with the addition of each composition for improving D-serine productivity divided by the turbidity after cultivation without the addition of the composition for improving D-serine productivity.

[0053] Furthermore, the growth promotion rates calculated in Comparative Examples 1 to 6 refer to the growth promotion rates when each D-serine-producing bacterium is cultured with the addition of only sialic acid so that the sialic acid content becomes 0.5 mmol / g equivalent.

[0054] (5) Preparation of culture supernatant The D-serine-producing bacteria cultured in the anaerobic workstation were removed from the workstation. Centrifugation was performed at 14,000 rpm for 10 minutes at 4°C under atmospheric pressure, and approximately 9 mL of crude culture supernatant was collected. The crude culture supernatant was then applied to a column equipped with a 3 kDa ultrafiltration membrane (3 kD Molcut; Millipore Merck). Centrifugation was performed at 14,000 rpm for 30 minutes at 4°C to remove high molecular weight fractions. The fraction that passed through the ultrafiltration membrane was used as the culture supernatant for D-serine measurement. These culture supernatants for D-serine measurement were used as samples for measuring D-serine concentrations in Examples 1 to 12 and Comparative Examples 1 to 6.

[0055] 2. Measurement of D-serine concentration o-Phthalaldehyde and N-isobutyryl-L-cysteine ​​were added to the culture supernatants for D-serine measurement in Examples 1 to 22 and Comparative Examples 1 to 6 to convert the D- and L-serine contained in each sample into fluorescently labeled diastereomers, which were then separated by UHPLC (Shimadzu Corporation).

[0056] To obtain accurate D-serine concentrations, the samples were treated with D-amino acid oxidase to convert them to keto acids that do not react with derivatization reagents. After derivatization under the same conditions, the samples were subjected to UHPLC again to confirm that the peaks on the chromatogram disappeared after enzymatic treatment. Calibration curves were prepared using 0.1, 0.5, 2.5, 12.5, and 25 μM D-serine and L-serine as standard substances, and quantification was performed after confirming that the measured values ​​were within this range. Note that the studies for Examples 1 to 12 and Comparative Examples 1 to 6 were performed with n=1, and the calculated values ​​were representative values.

[0057] The D-serine concentrations measured in Comparative Examples 1 to 6 refer to the D-serine concentrations after culturing each D-serine-producing bacterium with the addition of only sialic acid so that the sialic acid content becomes 0.5 mmol / g equivalent.

[0058] <Test Example 2> 1. Selection of Enterobacteriaceae and Preparation of Freeze-Concentrated Bacteria (1) Obtaining D-serine-producing bacteria Among the D-serine-producing bacteria, six strains corresponding to Phocaicola dorei and Bacteroides uniformis were obtained from JCM or DSMZ.

[0059] (2) Preparation of frozen concentrated bacterial cells The above six bacterial species were cultured in YCFA medium (JCM medium number 1130). The composition of the YCFA medium used is shown in Table 3.

[0060] [Table 3] The YCFA medium was sterilized by heating at 121°C for 15 minutes. The six D-serine-producing bacterial species were inoculated into individual sterilized media and anaerobically cultured at 37°C using an anaerobic workstation (Concept 400, Central Scientific Trading Co., Ltd.). The anaerobic workstation was operated by aerating with a mixed gas. The anaerobic gas ratios were 80% (v / v) nitrogen, 10% (v / v) carbon dioxide, and 10% (v / v) hydrogen. Each culture was concentrated by centrifugation, and glycerol was added to a concentration of 10% (v / v) to obtain various concentrated bacterial cells. The concentrated bacterial cells were then frozen at -80°C.

[0061] The frozen concentrated bacterial cells were then thawed, serially diluted, and plated on modified GAM broth agar medium to measure the viable bacterial count. All strains were confirmed to contain a viable bacterial count of 1.0E+07 cfu / mL or more.

[0062] (3) Preparation of a composition for improving D-serine productivity A commercially available reagent (purity 99.9% or higher) was used as sialic acid. A composition containing sialylgalacto-N-biose was prepared in the same manner as in Test Example 1.

[0063] (4) Cultivation of each D-serine-producing bacterium The above-mentioned frozen concentrated bacterial cells were thawed in an anaerobic workstation, inoculated into 10 mL of YCFA medium to a concentration of 1%, and cultured at 37°C for 16 hours in an incubator attached to the workstation.

[0064] The proportions of anaerobic gas aerated were 80% (v / v) nitrogen, 10% (v / v) carbon dioxide, and 10% (v / v) hydrogen. After cultivation, the cells were collected by centrifugation. Chromosomal DNA was then extracted using the DNeasy Blood & Tissue Kit (QIAGEN). The nucleotide sequence of the 16S rRNA gene was determined to confirm that the target bacterial species had been cultivated. Each composition for improving D-serine productivity was added so that the sialic acid content was 0.5 mmol / g equivalent. The turbidity after cultivation was measured at a wavelength of 660 nm. The growth promotion rate was calculated as the ratio of the turbidity after cultivation with the addition of each composition for improving D-serine productivity divided by the turbidity after cultivation without the addition of the composition for improving D-serine productivity.

[0065] Furthermore, the growth promotion rates calculated in Comparative Examples 7 to 12 refer to the growth promotion rates when each D-serine-producing bacterium was cultured with the addition of only sialic acid so that the sialic acid content was 0.5 mmol / g equivalent.

[0066] (5) Preparation of culture supernatant Culture supernatants for D-serine measurement were prepared in the same manner as in Test Example 1. These culture supernatants for D-serine measurement were used as samples for D-serine concentration measurement in Examples 13 to 18. In addition, as Comparative Examples 7 to 12, samples for D-serine concentration measurement were prepared by culturing each D-serine-producing bacterium with the addition of only sialic acid so that the sialic acid content was 0.5 mmol / g equivalent.

[0067] 2. Measurement of D-serine concentration In the same manner as in Test Example 1, the D-serine concentrations of the samples for measuring D-serine concentrations of Examples 13 to 18 and Comparative Examples 7 to 12 were measured.

[0068] <Test Results> Table 4 shows the components contained in the compositions for improving D-serine productivity, the species and species number of the D-serine-producing bacteria, the increased D-serine concentration, and the growth promotion rate of Examples 1 to 12 and Comparative Examples 1 to 6. Table 5 shows the components contained in the compositions for improving D-serine productivity, the species and species number of the D-serine-producing bacteria, the increased D-serine concentration, and the growth promotion rate of Examples 13 to 18 and Comparative Examples 7 to 12.

[0069] In Table 4, the components contained in each composition for improving D-serine productivity, the species of the D-serine-producing bacterium, the species number, the improved D-serine concentration, and the growth promotion rate are listed in the "Composition for improving D-serine productivity," "Containing species," "Strain number," "Improved concentration (μM)," and "Growth promotion rate" columns, respectively. The "Composition for improving D-serine productivity" column is further divided into "Sialic acid," "Galacto-N-biose," and "Lactose," and each component is marked with "〇" if it is contained, and "-" if it is not contained.

[0070] In Table 5, the components contained in each composition for improving D-serine productivity, the species of the D-serine-producing bacterium, the species number, the improved D-serine concentration, and the growth promotion rate are listed in the "Composition for improving D-serine productivity," "Containing species," "Strain number," "Improved concentration (μM)," and "Growth promotion rate" columns, respectively. The "Composition for improving D-serine productivity" column is further divided into "Sialic acid" and "Galacto-N-biose," and the presence of each component is marked with "○," while the absence of each component is marked with "-."

[0071] [Table 4]

[0072] [Table 5] As shown in Table 4, the growth promotion rates in Comparative Examples 1 to 6 and Examples 1 to 12 were not significantly different from the growth promotion rate of 1.0 obtained when the culture was performed without adding the composition for improving D-serine productivity. This confirmed that the compositions for improving D-serine productivity in Comparative Examples 1 to 6 and Examples 1 to 12 did not contribute to the promotion of growth of D-serine-producing bacteria.

[0073] The compositions for improving D-serine productivity in Comparative Examples 1 to 6 did not improve the D-serine concentration compared to culture without the addition of the compositions for improving D-serine productivity, confirming that sialic acid alone does not contribute to the D-serine productivity of D-serine-producing bacteria.

[0074] The compositions for improving D-serine productivity of Examples 1 to 12 all improved the D-serine concentration by 0.2 μM or more compared to culture without the addition of the composition for improving D-serine productivity. This confirmed that the compositions for improving D-serine productivity of Examples 1 to 12 can suitably improve the D-serine productivity of D-serine-producing bacteria.

[0075] Furthermore, as shown in Table 5, the growth promotion rates in Comparative Examples 7 to 12 and Examples 13 to 18 were not significantly different from the growth promotion rate of 1.0 obtained when the culture was performed without adding the composition for improving D-serine productivity. This confirmed that the compositions for improving D-serine productivity in Comparative Examples 7 to 12 and Examples 13 to 18 did not contribute to the promotion of growth of D-serine-producing bacteria.

[0076] The compositions for improving D-serine productivity in Comparative Examples 7 to 12 did not improve the D-serine concentration compared to culture without the addition of the compositions for improving D-serine productivity, confirming that sialic acid alone does not contribute to the D-serine productivity of D-serine-producing bacteria.

[0077] The compositions for improving D-serine productivity of Examples 13 to 18 all improved the D-serine concentration by 0.2 μM or more compared to culture without the addition of the composition for improving D-serine productivity. This confirmed that the compositions for improving D-serine productivity of Examples 13 to 18 can suitably improve the D-serine productivity of D-serine-producing bacteria. [Industrial Applicability]

[0078] According to the present invention, the D-serine productivity of D-serine-producing bacteria can be improved by adding a composition for improving D-serine productivity, thereby enabling the production of a high concentration of D-serine, a compound that is naturally present at an extremely low level.

Claims

1. A composition for improving D-serine productivity, comprising sialic acid and a sugar.

2. 2. The composition for improving D-serine productivity according to claim 1, wherein the sugar is galacto-N-biose.

3. 2. The composition for improving D-serine productivity according to claim 1, wherein the sugar is lactose.

4. 2. The composition for improving D-serine productivity according to claim 1, wherein the sugar is galactose.

5. It is used to improve the productivity of D-serine by D-serine-producing bacteria, 3. The composition for improving D-serine productivity according to claim 2, wherein the D-serine-producing bacterium is at least one selected from the group consisting of Phocaecola dorei, Phocaecola vulgatus, and Bacteroides uniformis.

6. It is used to improve the productivity of D-serine by D-serine-producing bacteria, 5. The composition for improving D-serine productivity according to claim 3, wherein the D-serine-producing bacterium is at least one selected from the group consisting of Focaecola vulgatus and Bacteroides uniformis.

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