CN110499345B - 一种维生素k2(MK-7型)的发酵方法 - Google Patents
一种维生素k2(MK-7型)的发酵方法 Download PDFInfo
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- CN110499345B CN110499345B CN201910822357.0A CN201910822357A CN110499345B CN 110499345 B CN110499345 B CN 110499345B CN 201910822357 A CN201910822357 A CN 201910822357A CN 110499345 B CN110499345 B CN 110499345B
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- 238000000855 fermentation Methods 0.000 title claims abstract description 165
- 230000004151 fermentation Effects 0.000 title claims abstract description 165
- PFRQBZFETXBLTP-UHFFFAOYSA-N Vitamin K2 Natural products C1=CC=C2C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C(=O)C2=C1 PFRQBZFETXBLTP-UHFFFAOYSA-N 0.000 title claims abstract description 41
- DKHGMERMDICWDU-GHDNBGIDSA-N menaquinone-4 Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 DKHGMERMDICWDU-GHDNBGIDSA-N 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 28
- 239000011700 menaquinone-7 Substances 0.000 title abstract description 27
- 229960005481 menatetrenone Drugs 0.000 title abstract description 26
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 76
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 68
- 239000001301 oxygen Substances 0.000 claims abstract description 68
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 62
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 41
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 41
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 36
- 239000008103 glucose Substances 0.000 claims abstract description 36
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 31
- 239000001963 growth medium Substances 0.000 claims abstract description 23
- 239000013589 supplement Substances 0.000 claims abstract description 11
- 244000063299 Bacillus subtilis Species 0.000 claims abstract description 9
- 235000014469 Bacillus subtilis Nutrition 0.000 claims abstract description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 51
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 49
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 42
- 238000009423 ventilation Methods 0.000 claims description 36
- 239000011780 sodium chloride Substances 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 239000001888 Peptone Substances 0.000 claims description 23
- 108010080698 Peptones Proteins 0.000 claims description 23
- 239000002609 medium Substances 0.000 claims description 23
- 235000019319 peptone Nutrition 0.000 claims description 23
- 230000001502 supplementing effect Effects 0.000 claims description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 21
- 244000068988 Glycine max Species 0.000 claims description 18
- 235000010469 Glycine max Nutrition 0.000 claims description 18
- 239000007836 KH2PO4 Substances 0.000 claims description 18
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 18
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 18
- 239000000843 powder Substances 0.000 claims description 18
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 claims description 17
- 235000019143 vitamin K2 Nutrition 0.000 claims description 13
- 239000011728 vitamin K2 Substances 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 10
- 241000894006 Bacteria Species 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 8
- 238000011218 seed culture Methods 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 4
- 238000011081 inoculation Methods 0.000 claims description 4
- 229920001817 Agar Polymers 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- 239000008272 agar Substances 0.000 claims description 3
- 229940041514 candida albicans extract Drugs 0.000 claims description 3
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 3
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000012138 yeast extract Substances 0.000 claims description 3
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 230000004060 metabolic process Effects 0.000 abstract description 5
- 241001052560 Thallis Species 0.000 abstract description 3
- 235000016709 nutrition Nutrition 0.000 abstract description 2
- 230000035764 nutrition Effects 0.000 abstract description 2
- 230000001276 controlling effect Effects 0.000 description 53
- 238000002474 experimental method Methods 0.000 description 17
- 235000011187 glycerol Nutrition 0.000 description 15
- 230000000694 effects Effects 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000000813 microbial effect Effects 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- MJVAVZPDRWSRRC-UHFFFAOYSA-N Menadione Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 1
- 241000589565 Flavobacterium Species 0.000 description 1
- ABSPRNADVQNDOU-UHFFFAOYSA-N Menaquinone 1 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(C)C(=O)C2=C1 ABSPRNADVQNDOU-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 230000003262 anti-osteoporosis Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000019175 phylloquinone Nutrition 0.000 description 1
- 239000011772 phylloquinone Substances 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 description 1
- 229960001898 phytomenadione Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- -1 platinum vitamin Chemical class 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 235000012711 vitamin K3 Nutrition 0.000 description 1
- 239000011652 vitamin K3 Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940041603 vitamin k 3 Drugs 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; 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
- C12N1/20—Bacteria; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/66—Preparation of oxygen-containing organic compounds containing the quinoid structure
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
项目 | 批次 | 发酵单位g/l | 体积L | 产量g |
实验1 | 4 | 80.8 | 36.1 | 2.92 |
实验5 | 4 | 68.6 | 36.2 | 2.48 |
实验6 | 4 | 75.4 | 36.0 | 2.71 |
实验7 | 4 | 76.9 | 36.0 | 2.77 |
实验8 | 4 | 75.4 | 35.9 | 2.70 |
X | 批次 | 发酵单位g/l | 体积L | 产量g |
0.2 | 4 | 72.4 | 36.1 | 2.61 |
0.3 | 4 | 79.9 | 36.2 | 2.89 |
0.4 | 4 | 80.4 | 36.0 | 2.89 |
0.5 | 4 | 81.5 | 36.0 | 2.93 |
0.6 | 4 | 80.7 | 35.9 | 2.89 |
0.7 | 4 | 80.3 | 36.0 | 2.89 |
Claims (2)
Priority Applications (1)
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CN201910822357.0A CN110499345B (zh) | 2019-09-02 | 2019-09-02 | 一种维生素k2(MK-7型)的发酵方法 |
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Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN111549079B (zh) * | 2020-06-18 | 2024-05-10 | 内蒙古金达威药业有限公司 | 一种采用微生物发酵法制备维生素k2的方法 |
CN112971148A (zh) * | 2021-04-20 | 2021-06-18 | 郑州路路通医药科技有限公司 | 一种钙维生素d维生素k片剂及其制备方法 |
CN113755402A (zh) * | 2021-10-12 | 2021-12-07 | 淮阴工学院 | 一种纳豆芽胞杆菌高密度发酵培养基及其高密度发酵方法 |
CN114790468A (zh) * | 2022-04-08 | 2022-07-26 | 浙江珲达生物科技有限公司 | 一种mk-7的发酵生产方法 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1803820A1 (en) * | 2005-12-29 | 2007-07-04 | Gnosis S.p.A. | A process for the preparation of vitamin K2 |
CN103571897A (zh) * | 2013-10-29 | 2014-02-12 | 中国科学院合肥物质科学研究院 | 一种维生素k2及其制备方法 |
CN104328064A (zh) * | 2014-09-16 | 2015-02-04 | 丽水双健生物工程有限公司 | 一种纳豆芽孢杆菌及其在发酵生产维生素k2中的应用 |
CN108410775A (zh) * | 2018-04-27 | 2018-08-17 | 江南大学 | 一株高产维生素k2(mk-7)的纳豆芽孢杆菌及其应用 |
CN109971788A (zh) * | 2019-03-11 | 2019-07-05 | 中国科学院合肥物质科学研究院 | 一种重组纳豆芽孢杆菌的构建方法及其发酵制备维生素k2的方法 |
CN110157654A (zh) * | 2019-05-21 | 2019-08-23 | 江南大学 | 一种纳豆芽孢杆菌重组菌及其构建方法与应用 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3834048B2 (ja) * | 2004-12-28 | 2006-10-18 | 株式会社日本生物科学研究所 | 納豆菌培養液に由来する食品の製造方法 |
-
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- 2019-09-02 CN CN201910822357.0A patent/CN110499345B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1803820A1 (en) * | 2005-12-29 | 2007-07-04 | Gnosis S.p.A. | A process for the preparation of vitamin K2 |
CN103571897A (zh) * | 2013-10-29 | 2014-02-12 | 中国科学院合肥物质科学研究院 | 一种维生素k2及其制备方法 |
CN104328064A (zh) * | 2014-09-16 | 2015-02-04 | 丽水双健生物工程有限公司 | 一种纳豆芽孢杆菌及其在发酵生产维生素k2中的应用 |
CN108410775A (zh) * | 2018-04-27 | 2018-08-17 | 江南大学 | 一株高产维生素k2(mk-7)的纳豆芽孢杆菌及其应用 |
CN109971788A (zh) * | 2019-03-11 | 2019-07-05 | 中国科学院合肥物质科学研究院 | 一种重组纳豆芽孢杆菌的构建方法及其发酵制备维生素k2的方法 |
CN110157654A (zh) * | 2019-05-21 | 2019-08-23 | 江南大学 | 一种纳豆芽孢杆菌重组菌及其构建方法与应用 |
Non-Patent Citations (2)
Title |
---|
Utilization of glucose-based medium and optimization of Bacillus subtilis natto growth parameters for vitamin K (menaquinone-7) production in biofilm reactors;Ehsan Mahdinia et al;《Biocatalysis and Agricultural Biotechnology》;20181231;第13卷;第219-224页 * |
纳豆芽孢杆菌生产维生素K2的连续发酵工艺优化;牟杰等;《食品工业科技》;20161231;第37卷(第19期);第157-161页 * |
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Denomination of invention: A fermentation method for vitamin k2 (MK-7 type) Granted publication date: 20210528 Pledgee: Fujian Straits bank Limited by Share Ltd. Fuqing branch Pledgor: FUJIAN KANGHONG BIOTECHNOLOGY Co.,Ltd. Registration number: Y2024350000040 |