WO2011052003A1 - Nouvelle souche bactérienne, culture, composition contenant le pigment caroténoïde et procédé de production du pigment caroténoïde - Google Patents

Nouvelle souche bactérienne, culture, composition contenant le pigment caroténoïde et procédé de production du pigment caroténoïde Download PDF

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WO2011052003A1
WO2011052003A1 PCT/JP2009/005663 JP2009005663W WO2011052003A1 WO 2011052003 A1 WO2011052003 A1 WO 2011052003A1 JP 2009005663 W JP2009005663 W JP 2009005663W WO 2011052003 A1 WO2011052003 A1 WO 2011052003A1
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carotenoid pigment
culture
carotenoid
strain
content
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Japanese (ja)
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松本光史
是 松永
田中剛
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Electric Power Development Co Ltd
Tokyo University of Agriculture and Technology NUC
University of Tokyo NUC
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Electric Power Development Co Ltd
Tokyo University of Agriculture and Technology NUC
University of Tokyo NUC
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Priority to PCT/JP2009/005663 priority Critical patent/WO2011052003A1/fr
Priority to JP2011538110A priority patent/JP5660543B2/ja
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P23/00Preparation of compounds containing a cyclohexene ring having an unsaturated side chain containing at least ten carbon atoms bound by conjugated double bonds, e.g. carotenes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20Bacteria; Culture media therefor
    • C12N1/205Bacterial isolates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12RINDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00Microorganisms ; Processes using microorganisms
    • C12R2001/01Bacteria or Actinomycetales ; using bacteria or Actinomycetales

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  • the present invention relates to a novel mutant strain of a bacterium belonging to the genus Sphingomonas, a culture obtained using the mutant strain, a carotenoid pigment-containing composition, and a method for producing a carotenoid pigment using the mutant strain. .
  • feed colored fried feed
  • feeds containing pigments such as astaxanthin may be used for fish species such as Thailand and rainbow trout that require vivid body colors.
  • Astaxanthin as an additive to deep-fried feed is sold by Roche as calorie pink (synthetic astaxanthin).
  • astaxanthin derived from nature has been attracting attention because of traceability problems and users' preference for natural products. Astaxanthin is widely distributed in fish such as red sea bream and salmon; crustaceans such as crabs, shrimps and krill. Therefore, a method for extracting astaxanthin from crustaceans has been proposed as a method for obtaining naturally-derived astaxanthin.
  • the extraction efficiency is low, there is a problem that the extraction amount is small and the cost is high.
  • due to the decrease in natural resources there were commercial problems in terms of securing resources.
  • Haematococcus pluvariis which is a green alga
  • Xanthophyllomyces dendrous house (formerly Phaffia rhodozyma), which is a red yeast
  • the amount of astaxanthin produced by Haematococcus pluvialis is about 43 mg / g dry weight (see Non-Patent Document 1).
  • Prokaryotic bacteria are one of the most promising microorganisms in the production of useful substances because they have a wide substrate utilization capacity, show a high growth rate in simple culture, and do not have a thick cell wall like yeast. It is. So far, in the production of astaxanthin by bacteria, 1.4 mg / g dry weight has been achieved with Escherichia coli gene recombinants (see Non-Patent Document 3). Moreover, in Bacillus firmus, the production amount of 0.05 mg / g dry weight was achieved (refer nonpatent literature 4). Furthermore, Paracoccus sp. In MBIC 1143, the production amount of 0.14 mg / g dry weight has been reported (see Non-Patent Document 5).
  • JPCMMB0017 strain (NITE P-48), which is a bacterium belonging to the genus Sphingomonas, has a carotenoid pigment producing ability (see Patent Document 1). ).
  • the present invention has been made in view of the above circumstances, and an object of the present invention is to provide a novel bacterium having a carotenoid pigment-producing ability and a method for producing a carotenoid pigment using the bacterium.
  • Sphingomonas sp. JPCC MB0017-6 strain (Accession number: NITE BP-808).
  • a culture obtained by culturing the bacterial strain described in (1) (2) A culture obtained by culturing the bacterial strain described in (1).
  • a method for producing a carotenoid pigment comprising the step of culturing the bacterial strain according to (1).
  • a novel bacterium capable of producing a carotenoid pigment and a method for producing a carotenoid pigment using the bacterium. Moreover, since the bacterium of the present invention has a high ability to produce carotenoid pigments, high-quality carotenoid pigments can be produced easily and in large quantities. As a result, an inexpensive carotenoid pigment can be provided.
  • the Sphingomonas sp. JPCC MB0017-6 strain (Accession number: NITE BP-808) of the present invention is a variant of the Sphingomonas sp. JPCMBB strain.
  • Sphingomonas sp. JPCMBB0017 strain may be abbreviated as “wild strain”.
  • “Sphingomonas sp. JPCC MB0017-6 strain (accession number: NITE BP-808)” is sometimes abbreviated as “mutant strain”.
  • the “carotenoid pigment” refers to a pigment having a polyene structure having 40 carbon atoms as a basic skeleton, and includes hydrocarbons such as carotene and lycopene, and alcohols such as xanthophyll, and ⁇ -carotene. Examples include various useful carotenoid pigments that are generated in the process of converting astaxanthin and ⁇ -carotene into astaxanthin.
  • carotenoid pigments include carotene, lycopene, astaxanthin, adonixanthin, zeaxanthin, adonilvin, canthaxanthin, cryptoxanthin, echinone, hydroechinone, lutein, fucoxanthin, anthaxanthin, violaxanthin, ⁇ - Examples include cryptoxanthin.
  • mutant strain of the present invention was obtained by performing chemical mutation on the wild strain. More specifically, it is as follows.
  • the wild strain was obtained by the applicant on December 3, 2004, from the National Institute for Product Evaluation Technology Patent Microorganism Depositary Center (2-5-8, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan) -0818)) (Accession number: NITE P-48).
  • the present inventors have acquired a wild strain from the nature upon deposit, and the acquisition procedure is shown below.
  • the culture was allowed to stand for 7 to 10 days at 25 ° C., and marine microorganisms forming orange and red colonies were obtained.
  • Wild strain is an absolute aerobic gram-negative bacilli. From the phylogenetic analysis of 16S rDNA, this wild strain belongs to ⁇ -Proteobacteria, forms a cluster with the genus Sphingomonas, and also contains the sphingolipid characteristic of the genus Sphingomonas. Has been confirmed to be a bacterium.
  • the wild strain was subjected to chemical mutation using a DNA alkylating agent according to the following procedure.
  • wild strains were cultured in marine broth (hereinafter abbreviated as MB) 2216 medium (manufactured by Becton Dickinson) for 24 hours and collected by centrifugation.
  • MB marine broth
  • 1 ⁇ 10 9 cells of JPCMBB0017 strain was transferred to 30-60 ° C. at 30 ° C. in 1 ml of pH 7.0 15 mM phosphate buffer containing 1.0-5.0% ethyl methanesulfonate (EMS). Incubation for min and mutagenesis was performed.
  • EMS ethyl methanesulfonate
  • the obtained cells were washed twice with phosphate buffered saline (hereinafter abbreviated as PBS), and then reincubated with the MB2216 medium at 30 ° C. for 2 hours.
  • PBS phosphate buffered saline
  • the obtained bacterial cells were applied to an MB agar medium and incubated at 30 ° C. for 3 to 7 days. As a result, mutant strains were obtained.
  • FIG. 1 shows imaging data of colonies of mutant and wild strains, respectively.
  • the right side is a mutant colony
  • the left side is a wild-type colony.
  • DNA base composition (GC content): 59.1 mol% Cellular lipid analysis Major quinone: Ubiquinone Q-10 fatty acid: 10: 0 3OH 0.26% 12: 0 2OH 0.13% 12: 0 3OH 0.30% 14: 0 0.17% 13: 0 2OH 0.24% 15: 0 1.32% 14: 0 2OH 3.05% 16: 0 5.82% 15: 0 2OH 2.58% 17: 0 ISO 0.08% 17: 1 w8c 2.83% 17: 1 w6c 2.95% 17: 0 1.39% 16: 1 2OH 0.09% 16: 0 2OH 1.40% 18: 1 w7c 71.90% 18: 1 w5c 0.39% 18: 0 0.20% 17: 0 ISO 3OH 1.61% 18: 1 2OH 0.24% 19: 0 10 methyl 0.42% Species with similar fatty acids: Sphingomonas paucimobilis Similarity (SI): 0.267
  • Bacteriochlorophyll production (anaerobic): not growing Bacteriochlorophyll production (aerobic): negative Presence of sphingolipid: + Salt (NaCl) requirement in growth: +
  • the mutant strain of the present invention is a novel bacterium having a carotenoid pigment producing ability significantly higher than that of the wild strain under the same conditions.
  • a bacterium having a high carotenoid pigment-producing ability has not been known so far in bacteria belonging to the genus Sphingomonas.
  • the mutant strain of the present invention is a bacterium belonging to the genus Sphingomonas, which has the ability to produce various carotenoid pigments and can produce a desired carotenoid pigment by adjusting the culture temperature. Has excellent properties not seen.
  • the mutant strain of the present invention has the accession number NITE BP-808 dated September 04, 2009, and the Patent Microorganism Deposit Center, National Institute of Technology and Evaluation (2-5 Kazusa Kamashichi, Kisarazu City, Chiba Prefecture, Japan) 8 (zip code 292-0818).
  • the culture obtained by culturing the mutant strain contains the mutant strain having the produced carotenoid pigment.
  • the culture may be used as it is for the intended purpose, or may be used after performing an arbitrary purification operation.
  • a composition containing a carotenoid pigment may be separated from the mutant after culturing, and the composition may be used for the intended use. Further, the composition is purified to improve purity. Carotenoid pigments may be used.
  • the method for producing a carotenoid pigment of the present invention includes a step of culturing the mutant strain of the present invention.
  • the composition of the carotenoid pigment produced by the mutant strain can be adjusted by appropriately adjusting the culture temperature.
  • Mutant strains can be cultured in the same manner as for wild strains. Specifically, it is as follows.
  • the medium is not particularly limited as long as it contains essential components such as a carbon source, a nitrogen source, inorganic salts, and trace components necessary for growth.
  • the carbon source include sugars such as glucose and sucrose; alcohols such as ethanol and glycerol.
  • the addition ratio of the carbon source is preferably about 0.5 to 3.0% by mass although it depends on the type of the carbon source.
  • the nitrogen source examples include sodium nitrate, ammonium nitrate, ammonium sulfate, potassium nitrate, ammonium chloride, urea and the like.
  • the addition ratio of the nitrogen source is preferably about 0.01% to 0.1% by mass, although it depends on the type of nitrogen source.
  • the inorganic salts include sodium chloride, sodium sulfate, calcium chloride, potassium chloride, sodium bicarbonate, potassium boride, strontium chloride, boric acid, sodium silicate, sodium fluoride, monopotassium phosphate, dipotassium phosphate, Examples thereof include monosodium phosphate, disodium phosphate, iron chloride, manganese chloride, manganese sulfate, magnesium chloride, and copper sulfate.
  • the addition ratio of the inorganic salts is preferably about 0.001% to 0.01% by mass although it depends on the kind of the inorganic salts.
  • Examples of the trace component include vitamins and trace metals.
  • the culture medium may contain optional components other than the essential components.
  • optional components include yeast extract, peptone, and tryptone.
  • the addition ratio of the optional component depends on the type of the optional component, but is preferably about 0.01% to 0.5% by mass.
  • the pH of the medium is preferably 6.0 to 8.0.
  • the culture temperature of the mutant strain can be arbitrarily selected within a range that does not hinder the growth of the mutant strain, but is preferably 20 to 45 ° C.
  • the production efficiency of the mutant carotenoid pigment varies depending on the culture temperature for each type of carotenoid pigment. That is, by appropriately adjusting the culture temperature of the mutant strain to a temperature suitable for the production of the desired carotenoid pigment, the production amount of the desired carotenoid pigment can be improved, and carotenoid pigments can be created separately.
  • the culture temperature is preferably 20 to 30 ° C, more preferably 23 to 27 ° C.
  • the culture temperature is preferably 25 to 40 ° C., more preferably 27 to 33 ° C.
  • the culture temperature is preferably 25 to 40 ° C., more preferably 33 to 37 ° C. In order to improve the amount of zeaxanthin produced, the culture temperature is preferably 30 to 45 ° C, more preferably 33 to 37 ° C. In order to improve the production amount of canthaxanthin, the culture temperature is preferably 25 to 45 ° C, more preferably 33 to 37 ° C. In order to improve the production amount of ⁇ -cryptoxanthin, the culture temperature is preferably 35 to 45 ° C., more preferably 38 to 42 ° C. In order to improve the production amount of ⁇ -carotene, the culture temperature is preferably 35 to 45 ° C, more preferably 38 to 42 ° C.
  • dye can be improved as follows by adjusting the culture
  • the astaxanthin content in the dried microbial cells of the mutant strain can be 0.04% by mass or more, and the astaxanthin content in all carotenoid pigments can be 30% by mass or more.
  • the echinenone content in the dry cells of the mutant strain can be 0.03% by mass or more, and the echinenone content in all carotenoid pigments can be 11% by mass or more.
  • the adonixanthin content in the dried cells of the mutant strain can be 0.04% by mass or more, and the adonixanthin content in all carotenoid pigments can be 6.5% by mass or more.
  • the zeaxanthin content in the dried cells of the mutant can be 0.1% by mass or more, and the zeaxanthin content in the total carotenoid pigment can be 19.5% by mass or more.
  • the canthaxanthin the canthaxanthin content in the dried microbial cells of the mutant strain can be 0.005% by mass or more, and the canthaxanthin content in all carotenoid pigments can be 1.5% by mass or more.
  • the ⁇ -cryptoxanthin content in the dried cells of the mutant can be 0.05% by mass or more, and the ⁇ -cryptoxanthin content in all carotenoid pigments can be 6% by mass or more.
  • the content of ⁇ -carotene in the dried cells of the mutant strain can be 0.5% by mass or more, and the content of ⁇ -carotene in all carotenoid pigments can be 65% by mass or more.
  • the carotenoid pigment-containing composition isolated from the mutant culture is a composition belonging to the genus Sphingomonas, including wild strains, obtained from a culture of bacteria having the ability to produce carotenoid pigments.
  • the content of various carotenoid pigments is remarkably high.
  • the content of specific carotenoid pigments such as astaxanthin, zeaxanthin, ⁇ -carotene can be greatly improved. Therefore, the carotenoid pigment-containing composition of the present invention is extremely useful.
  • the production amount (content) of the total carotenoid pigment in the mutant generally improves as the culture temperature increases.
  • the culture temperature is preferably 20 ° C. or higher, more preferably 23 ° C. or higher
  • the content of the total carotenoid pigment in the dried microbial cells of the mutant strain can be 0.12% by mass or higher.
  • dye in the dry microbial cell of a mutant can be made into 0.25 mass% or more by making culture
  • dye in the dry microbial cell of a mutant can be 0.55 mass% or more by making culture
  • dye in the dry microbial cell of a mutant can be 0.78 mass% or more by making culture
  • the culture time depends on the culture temperature, it is usually preferably 1 to 3 days.
  • the culture method may be appropriately selected depending on the type of medium, such as stationary culture, shaking culture, and stirring culture. And it is preferable to carry out aeration culture.
  • the carotenoid pigment can be separated from the culture or from the sediment recovered by centrifugation of the culture. For example, the culture or sediment is washed as necessary, and then subjected to freeze-drying or the like to obtain dry cells. And an organic solvent is added to the obtained dry microbial cell, carotenoid pigment
  • dye is extracted in this organic solvent, and this extraction operation is repeated in multiple times as needed. Subsequently, the carotenoid pigment is obtained by removing the solvent by a technique such as vacuum concentration.
  • the organic solvent used for extraction is not particularly limited as long as it can dissolve the carotenoid pigment, and any of a polar solvent and a nonpolar solvent can be used.
  • a polar solvent and a nonpolar solvent Preferable examples include hydrocarbons such as hexane; ketones such as acetone; alcohols such as methanol, ethanol and 2-propanol; esters such as ethyl acetate; halogenated hydrocarbons such as dichloromethane and chloroform.
  • Nitriles such as acetonitrile can be exemplified.
  • An organic solvent may be used individually by 1 type, and may use 2 or more types together. When two or more kinds are used in combination, the combination and ratio may be arbitrarily selected according to the purpose. These organic solvents can also be used for the purification of carotenoid pigments.
  • Carotenoid pigments can be identified, for example, by comparing the analysis data with the analysis data of known compounds. Any analysis method may be used as long as it can acquire data related to the structure. For example, a commonly used analysis method such as HPLC, absorbance analysis, NMR, or LC / MS may be used. For example, if a calibration curve is prepared at the time of analysis by HPLC, the content of each component in the obtained composition can also be quantified.
  • Carotenoid pigments can also be produced by recovering zooplankton. According to this production method, a feed enriched with carotenoid pigments can also be provided.
  • zooplankton examples include rotifers, artemia, daphnia and the like. These zooplanktons are biologically enriched by preying on mutants, and the resulting zooplankton cultures have a much higher concentration of carotenoid pigments than those produced by conventional bacterial cultures. And its utility value is extremely high.
  • a feed enriched with carotenoid pigments by zooplankton is suitable for use in cultured fish.
  • Some juveniles feed on crustacean plankton containing carotenoid pigments, and it is known that the color of fish is affected by this feeding.
  • the feed produced by the above method is fed as a fried food, the concentrated carotenoid pigment can be fed, and the fish can be colored more efficiently than before.
  • Example 1 ⁇ Production of carotenoid pigment using mutant strain (1)> MB2216 (37.4 g), 3 g of glucose and 1 L of pure water were mixed to prepare a medium, and the medium was sterilized at 121 ° C. for 20 minutes in a 1 L media bottle. Next, after cooling the medium to room temperature, 200 ml was dispensed into a 1 L Erlenmeyer flask in a clean bench, and 10 ml of a mutant strain previously cultured in a 10 ml L-shaped test tube was inoculated into the dispensed medium. did. The pH of the medium after inoculation was 7.6 to 7.8.
  • the mutant strain was cultured by shaking for 2 days under the conditions of a culture temperature of 30 ° C. and a stirring speed of 120 rpm using a constant temperature shake incubator bioshaker (trade name, manufactured by Taitec Co., Ltd.). Subsequently, the culture was centrifuged to recover the mutant strain, freeze-dried, and then crushed in a mortar to obtain powdered dry cells. And the carotenoid pigment
  • dye was extracted and isolate
  • the separated carotenoid pigment was dissolved in acetone, and impurities were removed from the obtained solution using a filter to obtain a sample for absorption spectrum analysis. Then, HPLC analysis and absorption spectrum analysis were performed under the following conditions. Calculate the ratio of the content of each carotenoid pigment from the ratio of peak intensity (area value) in the profile of the carotenoid pigment at the time of HPLC analysis, and calculate the total carotenoid pigment content (total of carotenoid pigments) from the data at the time of absorption spectrum analysis. Content) and the content of each carotenoid pigment was calculated from these values.
  • HPLC analyzer LC-VP series (manufactured by Shimadzu Corporation) Column: Reversed phase column Symmetry C18 (5 ⁇ m, 4.6 ⁇ 250 mm) (manufactured by Waters) Column temperature: 40 ° C Mobile phase: Mixed solvent of acetonitrile / methanol / 2-propanol (45/3/2, volume ratio) Flow rate of mobile phase: 0.5 mL / min (absorption spectrum analysis) Spectrophotometer: UV-2400 (manufactured by Shimadzu Corporation) Cell: 1cm width
  • the content of total carotenoid pigment in 1 g of dry cells was 1.246 mg (0.125% by mass), and the content of astaxanthin in 1 g of dry cells was 0.16 mg (0.016% by mass). Met. The content of astaxanthin in the total carotenoid pigment was 12.8% by mass.
  • the content of total carotenoid pigment in the mutant strain is about 8 times that of the wild strain, and the content of astaxanthin in the mutant strain is It was about 16 times the wild type.
  • the container was set in a reaction part of a microorganism culture apparatus, and the medium was cooled to room temperature, and then 200 ml of a mutant strain previously cultured in a 1 L Erlenmeyer flask in a clean bench was inoculated into the medium.
  • the pH of the medium after inoculation was 7.6 to 7.8.
  • the mutant strain is shaken for 2 days under the conditions of a culture temperature of 25 ° C., a stirring speed of 200 rpm, and an aeration rate of 1 vvm (aeration rate (volume) per minute is 1 times that of the culture solution (4.2 L)). Cultured.
  • Example 3 ⁇ Production of carotenoid pigment using mutant strain (3)> The carotenoid pigment was separated and the content of each carotenoid pigment was calculated in the same manner as in Example 2 except that the culture temperature of the mutant strain was 30 ° C. instead of 25 ° C. Table 2 shows the composition of the carotenoid pigment in 1 g of the obtained dried cells. As can be seen from Table 2, ⁇ -carotene had the highest content in all carotenoid pigments.
  • Example 4 ⁇ Production of carotenoid pigment using mutant strain (4)> Carotenoid pigments were separated in the same manner as in Example 2 except that the culture temperature of the mutant strain was 35 ° C instead of 25 ° C, and the content of each carotenoid pigment was calculated. Table 3 shows the composition of the carotenoid pigment in 1 g of the obtained dried cells. As is clear from Table 3, ⁇ -carotene had the highest content in all carotenoid pigments.
  • Example 5 ⁇ Production of carotenoid pigment using mutant strain (5)> Carotenoid pigments were separated and the content of each carotenoid pigment was calculated in the same manner as in Example 2 except that the culture temperature of the mutant strain was 40 ° C instead of 25 ° C. Table 4 shows the composition of the carotenoid pigment in 1 g of the obtained dried cells. As is clear from Table 4, ⁇ -carotene had the highest content among all carotenoid pigments.
  • each carotenoid pigment could be improved by adjusting the culture temperature of the mutant strain. Specifically, astaxanthin is cultured at 25 ° C., echinenone is cultured at 30 ° C., adonixanthin, zeaxanthin and canthaxanthin are cultured at 35 ° C., and ⁇ -cryptoxanthin and ⁇ -carotene are cultured at 40 ° C. , Each had the highest content. Thus, the desired carotenoid pigment was efficiently obtained by appropriately adjusting the culture temperature.
  • the present invention is extremely useful industrially because it can be used to manufacture health food ingredients and feed additives.

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Abstract

L'invention concerne une nouvelle bactérie capable de produire un pigment caroténoïde et un procédé de production du pigment caroténoïde à l'aide de ladite bactérie. De façon spécifique, l'invention concerne une souche Sphingomonas JPCC MB0017-6 (dépôt No. NITE BP-808); une culture obtenue par culture de ladite souche bactérienne; une composition contenant un pigment caroténoïde séparée de ladite culture; et un procédé de production du pigment caroténoïde qui comprend une étape de culture de ladite souche bactérienne.
PCT/JP2009/005663 2009-10-27 2009-10-27 Nouvelle souche bactérienne, culture, composition contenant le pigment caroténoïde et procédé de production du pigment caroténoïde Ceased WO2011052003A1 (fr)

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JP2011538110A JP5660543B2 (ja) 2009-10-27 2009-10-27 新規細菌株、培養物及びカロテノイド色素の製造方法

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Cited By (3)

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US12252513B2 (en) 2018-07-16 2025-03-18 Lumen Bioscience, Inc. Thermostable phycobiliproteins produced from recombinant arthrospira
US12447202B2 (en) 2018-05-17 2025-10-21 Lumen Bioscience, Inc. Arthrospira platensis oral vaccine delivery platform
US12503682B2 (en) 2019-07-03 2025-12-23 Lumen Bioscience, Inc. Arthrospira platensis non-parenteral therapeutic delivery platform

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