CN117106631A - Coenzyme Q10 fermentation medium, mixed feed supplement liquid, low cost and clean fermentation process - Google Patents
Coenzyme Q10 fermentation medium, mixed feed supplement liquid, low cost and clean fermentation process Download PDFInfo
- Publication number
- CN117106631A CN117106631A CN202310880697.5A CN202310880697A CN117106631A CN 117106631 A CN117106631 A CN 117106631A CN 202310880697 A CN202310880697 A CN 202310880697A CN 117106631 A CN117106631 A CN 117106631A
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- Prior art keywords
- fermentation
- coenzyme
- vitamin
- culture
- sulfate
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- 238000000855 fermentation Methods 0.000 title claims abstract description 111
- 230000004151 fermentation Effects 0.000 title claims abstract description 111
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 title claims abstract description 57
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 235000017471 coenzyme Q10 Nutrition 0.000 title claims abstract description 56
- 229940110767 coenzyme Q10 Drugs 0.000 title claims abstract description 55
- 239000007788 liquid Substances 0.000 title claims abstract description 42
- 239000006052 feed supplement Substances 0.000 title claims abstract description 10
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims abstract description 46
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 46
- 239000001963 growth medium Substances 0.000 claims abstract description 30
- 229930003270 Vitamin B Natural products 0.000 claims abstract description 27
- 235000019156 vitamin B Nutrition 0.000 claims abstract description 27
- 239000011720 vitamin B Substances 0.000 claims abstract description 27
- 239000002609 medium Substances 0.000 claims abstract description 24
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract description 23
- 239000001110 calcium chloride Substances 0.000 claims abstract description 23
- 229910001628 calcium chloride Inorganic materials 0.000 claims abstract description 23
- 229910000365 copper sulfate Inorganic materials 0.000 claims abstract description 23
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims abstract description 23
- 229910001629 magnesium chloride Inorganic materials 0.000 claims abstract description 23
- 229940099596 manganese sulfate Drugs 0.000 claims abstract description 23
- 239000011702 manganese sulphate Substances 0.000 claims abstract description 23
- 235000007079 manganese sulphate Nutrition 0.000 claims abstract description 23
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 claims abstract description 23
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims abstract description 23
- 235000019796 monopotassium phosphate Nutrition 0.000 claims abstract description 23
- 239000011780 sodium chloride Substances 0.000 claims abstract description 23
- 239000011790 ferrous sulphate Substances 0.000 claims abstract description 22
- 235000003891 ferrous sulphate Nutrition 0.000 claims abstract description 22
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims abstract description 22
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims abstract description 22
- 239000002994 raw material Substances 0.000 claims abstract description 17
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims abstract description 16
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 16
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract description 16
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims abstract description 16
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims abstract description 14
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims abstract description 10
- OQVYMXCRDHDTTH-UHFFFAOYSA-N 4-(diethoxyphosphorylmethyl)-2-[4-(diethoxyphosphorylmethyl)pyridin-2-yl]pyridine Chemical compound CCOP(=O)(OCC)CC1=CC=NC(C=2N=CC=C(CP(=O)(OCC)OCC)C=2)=C1 OQVYMXCRDHDTTH-UHFFFAOYSA-N 0.000 claims abstract description 8
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 8
- 239000011609 ammonium molybdate Substances 0.000 claims abstract description 8
- 235000018660 ammonium molybdate Nutrition 0.000 claims abstract description 8
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 claims abstract description 8
- 229940010552 ammonium molybdate Drugs 0.000 claims abstract description 8
- 229960002685 biotin Drugs 0.000 claims abstract description 8
- 235000020958 biotin Nutrition 0.000 claims abstract description 8
- 239000011616 biotin Substances 0.000 claims abstract description 8
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004327 boric acid Substances 0.000 claims abstract description 8
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims abstract description 8
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 8
- 239000011718 vitamin C Substances 0.000 claims abstract description 8
- 229930003427 Vitamin E Natural products 0.000 claims abstract description 7
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims abstract description 7
- 235000019165 vitamin E Nutrition 0.000 claims abstract description 7
- 239000011709 vitamin E Substances 0.000 claims abstract description 7
- 229940046009 vitamin E Drugs 0.000 claims abstract description 7
- 238000012258 culturing Methods 0.000 claims description 23
- 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 description 21
- 239000008103 glucose Substances 0.000 claims description 21
- 239000001888 Peptone Substances 0.000 claims description 20
- 108010080698 Peptones Proteins 0.000 claims description 20
- 239000000284 extract Substances 0.000 claims description 20
- 235000019319 peptone Nutrition 0.000 claims description 20
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 claims description 18
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 claims description 18
- 235000019837 monoammonium phosphate Nutrition 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 241001052560 Thallis Species 0.000 claims description 15
- 238000005273 aeration Methods 0.000 claims description 15
- 235000015278 beef Nutrition 0.000 claims description 15
- UFMZWBIQTDUYBN-UHFFFAOYSA-N cobalt dinitrate Chemical compound [Co+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O UFMZWBIQTDUYBN-UHFFFAOYSA-N 0.000 claims description 15
- 229910001981 cobalt nitrate Inorganic materials 0.000 claims description 15
- WFLYOQCSIHENTM-UHFFFAOYSA-N molybdenum(4+) tetranitrate Chemical compound [N+](=O)([O-])[O-].[Mo+4].[N+](=O)([O-])[O-].[N+](=O)([O-])[O-].[N+](=O)([O-])[O-] WFLYOQCSIHENTM-UHFFFAOYSA-N 0.000 claims description 15
- 239000001509 sodium citrate Substances 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 15
- 229940038773 trisodium citrate Drugs 0.000 claims description 15
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 15
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 15
- 229960001763 zinc sulfate Drugs 0.000 claims description 15
- 230000001954 sterilising effect Effects 0.000 claims description 14
- 239000006012 monoammonium phosphate Substances 0.000 claims description 13
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 claims description 13
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 13
- 230000012010 growth Effects 0.000 claims description 12
- 238000011081 inoculation Methods 0.000 claims description 10
- 230000001133 acceleration Effects 0.000 claims description 9
- 238000012807 shake-flask culturing Methods 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 8
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 229930182817 methionine Natural products 0.000 claims description 8
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 claims description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 5
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 5
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 5
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 5
- 230000003698 anagen phase Effects 0.000 claims description 5
- 229940041514 candida albicans extract Drugs 0.000 claims description 5
- 239000002054 inoculum Substances 0.000 claims description 5
- 235000013372 meat Nutrition 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000012138 yeast extract Substances 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
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- 235000010374 vitamin B1 Nutrition 0.000 description 4
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- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
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- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- 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
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Abstract
The invention discloses a coenzyme Q10 fermentation medium, mixed feed supplement liquid and a low-cost clean fermentation process, and relates to the field of coenzyme Q10 production. The fermentation medium comprises the following raw materials in concentration: 8.5-10g/L of sodium chloride, 2.0-13g/L of potassium dihydrogen phosphate, 7.2-11.0g/L of disodium hydrogen phosphate, 0.5-2g/L of magnesium chloride, 0.1-0.6g/L of calcium chloride, 0.01-0.05g/L of ferrous sulfate, 0.01-0.04g/L of manganese sulfate, 0.005-0.01g/L of copper sulfate, 0.004-0.02g/L of boric acid, 0.003-0.04g/L of potassium manganate, 0.001-0.01g/L of ammonium molybdate, 0.4-1g/L of tyrosine, 10.2-0.5mg/L of vitamin B, 21-3mg/L of vitamin B, 61-2mg/L of vitamin B, 120.05-1mg/L of vitamin C, 100-500mg/L of vitamin E and 0.01-0.07mg/L of biotin. The invention realizes the high-efficiency production of the coenzyme Q10 by proper nutrition ratio based on the inorganic salt culture medium, simultaneously adopts high-concentration feed supplement liquid, effectively reduces the fermentation volume, reduces the production cost, can improve the yield and the purity of the coenzyme Q10, has good economic benefit and environmental protection benefit, and has wide application prospect and market value.
Description
Technical Field
The invention relates to the field of coenzyme Q10 production, in particular to a coenzyme Q10 fermentation medium, mixed feed supplement liquid and a low-cost clean fermentation process.
Background
Coenzyme Q10 (CoQ 10), also known as ubiquinone, is a fat-soluble vitamin-like substance that is widely present in animals and plants, and is also a coenzyme naturally occurring in the human body. It plays a plurality of important biological functions in the organism, mainly comprising the following aspects: (1) as a carrier on the mitochondrial electron transport chain: coenzyme Q10 is one of the key components in the mitochondrial electron transport chain, and is capable of transporting intracellular electrons from substrates such as NADH to respiratory complex I, and thus involved in ATP synthesis. (2) antioxidant effect: coenzyme Q10 has powerful antioxidant effect, and can eliminate free radical, reduce aerobic oxidative stress and inflammatory reaction, and protect cell from oxidative damage. (3) maintaining cardiovascular health: coenzyme Q10 is involved in regulating myocardial contractility, promoting vasodilation, lowering blood pressure, etc., and has important protective effects on cardiovascular health. (4) enhancing immunity: coenzyme Q10 can enhance immunity and anti-tumor effect, and promote proliferation and activity of immunocyte. (5) deferring aging: coenzyme Q10 also can delay the aging process of cells and organs and improve the anti-aging capability of organisms. Because of its important biological functions and wide application value, coenzyme Q10 is widely used in the fields of medicine, health products, foods, etc.
Currently, the production of coenzyme Q10 is mainly carried out by two methods, namely a chemical method and a biological method. Chemical synthesis is one of the main methods currently used for the industrial-scale production of coenzyme Q10. The method takes natural coenzyme Q10 as a raw material, and obtains high-purity coenzyme Q10 through a series of chemical reactions such as oxidation-reduction reaction, alkylation reaction and the like, and through repeated refining and purification. The chemical synthesis method can realize industrialized mass production, but also has the problems of high treatment difficulty of organic waste, difficult 100% purity of products and the like. The biological rule employs a microbial fermentation to produce coenzyme Q10, which is carried out under optimized fermentation conditions using a microorganism suitable for the production of coenzyme Q10. Microbial self-synthesized coenzyme Q10 is of increasing interest because it is more pure and bioavailable than chemical synthesis. However, since the fermentation production of coenzyme Q10 is a complicated process, there are some technical and technological problems, mainly including the following aspects:
(1) The strain breeding difficulty is high: most of the strains used for coenzyme Q10 production at present come from microorganisms which are difficult to separate and screen in natural environment, so the strain breeding difficulty is high.
(2) The fermentation condition is difficult to control: the production of coenzyme Q10 requires stringent fermentation conditions such as temperature, pH, redox potential, etc., which have a great influence on the growth and metabolism of the strain, but are difficult to control.
(3) The yield is low: the current fermentation production yield of coenzyme Q10 is low, and especially in the traditional liquid state fermentation, only tens to hundreds of milligrams of products can be produced per liter of fermentation broth.
(4) The cost is high: high purity coenzyme Q10 is expensive, which is closely related to the specific media, equipment and technology required in its production. Meanwhile, the current production scale is relatively small, so that the situation of high cost is caused.
(5) Pollution problem: the fermentation production of coenzyme Q10 is susceptible to microbial contamination and organic contamination, which presents certain challenges to the purity and stability of the product.
In view of the above, the fermentation production of coenzyme Q10 still has some problems and difficulties, and further research and optimization are required in the aspects of strain breeding, fermentation condition control, yield improvement, cost reduction, pollution control and the like.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a coenzyme Q10 fermentation medium, mixed feed supplement liquid and a low-cost clean fermentation process, and the method is based on an inorganic salt medium, and realizes the efficient production of coenzyme Q10 by optimizing nutrition ratio and adjusting related parameters. Meanwhile, high-concentration feed supplement liquid is adopted in the fermentation process, so that the fermentation volume is effectively reduced, the production cost is reduced, the yield and purity of coenzyme Q10 can be improved, good economic benefit and environmental benefit are achieved, and the method has wide application prospect and market value.
In order to achieve the technical purpose, the invention mainly adopts the following technical scheme:
in a first aspect, the invention discloses a coenzyme Q10 fermentation medium comprising the following concentrations of raw materials: 8.5-10g/L of sodium chloride, 2.0-13g/L of potassium dihydrogen phosphate, 7.2-11.0g/L of disodium hydrogen phosphate, 0.5-2g/L of magnesium chloride, 0.1-0.6g/L of calcium chloride, 0.01-0.05g/L of ferrous sulfate, 0.01-0.04g/L of manganese sulfate, 0.005-0.01g/L of copper sulfate, 0.004-0.02g/L of boric acid, 0.003-0.04g/L of potassium manganate, 0.001-0.01g/L of ammonium molybdate, 0.4-1g/L of tyrosine, 10.2-0.5mg/L of vitamin B, 21-3mg/L of vitamin B, 61-2mg/L of vitamin B, 120.05-1mg/L of vitamin C, 100-500mg/L of vitamin E and 0.01-0.07mg/L of biotin.
In a second aspect, the invention discloses a low cost, clean fermentation process for coenzyme Q10, comprising the steps of:
(1) Seed liquid culture: firstly, performing activation culture on a beef extract peptone flat plate, picking up bacterial colonies, placing the bacterial colonies into a shake flask culture medium, and performing shake flask culture to obtain shake flask seed liquid;
(2) Primary seed tank culture: inoculating the shake flask seed liquid into a culture medium of a first-stage seed tank according to an inoculum size of 1-5% for culture to obtain a first-stage seed liquid in a good growth state and a logarithmic growth phase;
(3) Culturing in a secondary seed tank: inoculating the primary seed liquid of the primary seed tank into a culture medium of the secondary seed tank according to the inoculation amount of 1-5% to culture, so as to obtain the secondary seed liquid in a good growth state and a logarithmic growth phase;
(4) Culturing in a fermentation tank: inoculating the secondary seed liquid into a fermentation tank according to 10-30% of inoculum size for culturing, and stopping fermentation when the thalli begin to rapidly descend;
in the fermentation tank, the coenzyme Q10 fermentation medium comprises the following raw materials with the concentration: 8.5-10g/L of sodium chloride, 2.0-13g/L of potassium dihydrogen phosphate, 7.2-11.0g/L of disodium hydrogen phosphate, 0.5-2g/L of magnesium chloride, 0.1-0.6g/L of calcium chloride, 0.01-0.05g/L of ferrous sulfate, 0.01-0.04g/L of manganese sulfate, 0.005-0.01g/L of copper sulfate, 0.004-0.02g/L of boric acid, 0.003-0.04g/L of potassium manganate, 0.001-0.01g/L of ammonium molybdate, 0.4-1g/L of tyrosine, 10.2-0.5mg/L of vitamin B, 21-3mg/L of vitamin B, 61-2mg/L of vitamin B, 120.05-1mg/L of vitamin C, 100-500mg/L of vitamin E and 0.01-0.07mg/L of biotin.
In a preferred embodiment of the present invention, in step (1), the beef extract peptone slab comprises the following concentrations of raw materials: 5-10g of beef extract, 6-10g of peptone, 1L of water and pH of 6.8-7.2; the shake flask culture medium comprises the following raw materials in concentration: 3-10g/L of peptone zymolyte, 5-12g/L of yeast extract powder, 1-3g/L of common meat extract, 2-10g/L of glucose, 2-5g/L of trisodium citrate, 1-5g/L of monopotassium phosphate, 0.5-3g/L of sodium chloride, 0.5-2g/L of magnesium chloride, 0.1-2g/L of calcium chloride, 0.01-0.5g/L of copper sulfate, 0.01-0.7g/L of cobalt nitrate, 0.1-0.9g/L of zinc sulfate, 0.1-0.5g/L of manganese sulfate, 0.01-0.4g/L of L molybdenum nitrate and 0.01-0.4g/L of ferrous sulfate; sterilizing at 121deg.C for 30min at pH 6.8-7.2.
Further, in the step (1), the activation culture temperature is 28-32 ℃, and the culture is carried out for 2-3 days; the culture temperature of the shake flask is 28-32 ℃, the rotating speed is 200-250rpm, and the culture is carried out for 12-24 hours.
In a preferred embodiment of the present invention, in step (2), the medium of the primary seed tank comprises the following concentrations of raw materials: 2-10g/L of glucose, 2-5g/L of trisodium citrate, 1-5g/L of monopotassium phosphate, 0.5-3g/L of sodium chloride, 0.5-2g/L of magnesium chloride, 5-10g/L of ammonium sulfate, 1-5g/L of monoammonium phosphate, 0.1-2g/L of calcium chloride, 0.01-0.5g/L of copper sulfate, 0.01-0.7g/L of cobalt nitrate, 0.1-0.9g/L of zinc sulfate, 0.1-0.5g/L of manganese sulfate, 0.01-0.4g/L of molybdenum nitrate and 0.01-0.4g/L of ferrous sulfate; sterilizing at 121deg.C for 30min at pH of 6.8-7.2; the culture temperature of the first-stage seed tank is 28-32 ℃, the tank pressure is 0.02-0.05Mpa, the aeration ratio is 0.5-1.0, the stirring rotation speed is 200-300rpm, and the culture is carried out for 23-40h.
In a preferred embodiment of the invention, in step (3), the medium of the secondary seed tank comprises the following concentrations of raw materials: 2-10g/L of glucose, 2-5g/L of trisodium citrate, 1-5g/L of monopotassium phosphate, 0.5-3g/L of sodium chloride, 0.5-2g/L of magnesium chloride, 5-10g/L of monoammonium phosphate, 0.1-2g/L of calcium chloride, 0.01-0.5g/L of copper sulfate, 0.01-0.7g/L of cobalt nitrate, 0.1-0.9g/L of zinc sulfate, 0.1-0.5g/L of manganese sulfate, 0.01-0.4g/L of molybdenum nitrate and 0.01-0.4g/L of ferrous sulfate; sterilizing at 121deg.C for 30min at pH of 6.8-7.2; the culture temperature of the secondary seed tank is 28-32 ℃, the tank pressure is 0.02-0.05Mpa, the aeration ratio is 0.5-1.0, the stirring rotation speed is 200-300rpm, and the culture is carried out for 23-40h.
In a preferred embodiment of the present invention, in step (4), the fermenter culture temperature is 28-32 ℃, the tank pressure is 0.02-0.05MPa, the aeration ratio is 0.5-1.0, and the stirring rotation speed is 100-200rpm.
In a preferred embodiment of the present invention, in step (4), the method further comprises the step of feeding a carbon source: glucose, sucrose or glycerol with the mass fraction of 70-80% is used as a carbon source, the carbon source is fed in from 12-15h after fermentation starts, the flow acceleration is 0.5%/h-1.5%/h of the total fermentation volume, the fermentation lasts for 100-130h, and the pH of the fermentation is controlled to be 6.8-7.2 by pure ammonia water during the fermentation, so that the fermentation is kept stable.
In a preferred embodiment of the present invention, in step (4), the method further includes a step of feeding the mixed feed solution: the method comprises the steps of feeding 10-20g/L tryptophan, 30-50g/L tyrosine, 20-40g/L phenylalanine, 5-10g/L methionine, 80-100g/L monoammonium phosphate and 15-20g/L vitamin B from 30 hours after fermentation starts, controlling the flow acceleration to be 1% of the total fermentation volume per hour, and continuing until the fermentation is finished.
In a third aspect, the invention discloses a mixed feed supplement liquid for coenzyme Q10 fermentation, which comprises the following raw materials in concentration: 10-20g/L tryptophan, 30-50g/L tyrosine, 20-40g/L phenylalanine, 5-10g/L methionine, 80-100g/L monoammonium phosphate and 15-20g/L vitamin B.
Compared with the prior art, the invention has the following beneficial effects:
1. the fermentation efficiency is improved: the use of an all inorganic salt medium can provide all the necessary minerals and nutrients needed by the microorganism, which helps to optimize the metabolic processes of the cells and to increase the fermentation efficiency. In addition, the high-concentration feed medium can further provide additional nutrients required by microorganisms and accelerate the growth and propagation of the microorganisms.
2. The cost is reduced: compared with the traditional organic culture medium, the all-inorganic salt culture medium is cheaper, and the production cost can be reduced to a certain extent. In addition, the high-concentration feed medium can achieve better nutrition effect through less addition amount, so that waste of raw materials is reduced.
3. The product quality is improved: the use of an all inorganic salt medium and a high concentration of feed medium can help the microorganism grow and reproduce better, resulting in more metabolites. These metabolites may have higher purity, better stability and lower contaminant content, thereby improving product quality.
4. The use of an all inorganic salt medium and a high concentration feed medium can also reduce the difficulty of post-treatment. As the culture medium does not contain organic components, the metabolites produced by microorganisms are fewer, thus reducing the workload of subsequent cleaning and treatment and simultaneously reducing the difficulty of wastewater and waste gas treatment.
Detailed Description
The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In embodiments of the invention, the method may be applied to any coenzyme Q10 producing strain, and as a specific embodiment, the strain used is rhodobacter sphaeroides. Of course, any other species that produces coenzyme Q10 may be used.
Example 1:
take the production of 1000L of coenzyme Q10 as an example:
1. culturing fermentation seed liquid:
the colonies are activated by using a beef extract peptone flat plate, the culture temperature is 30 ℃, after 3d of culture, a plurality of colonies are picked up into a shake flask culture medium, and the shake flask is placed into a shaking table with the temperature of 30 ℃ and the rotating speed of 225rpm for culture for 18 hours, so as to obtain seed liquid.
Wherein, beef extract peptone flat plate formula: 5g of beef extract, 6g of peptone and 1L of water, and regulating the pH to 6.8;
seed shake flask medium formula: 3g/L of peptone zymolyte, 5g/L of yeast extract powder, 1g/L of common meat extract, 2g/L of glucose, 2g/L of trisodium citrate, 1g/L of monopotassium phosphate, 0.5g/L of sodium chloride, 0.5g/L of magnesium chloride, 0.1g/L of calcium chloride, 0.01g/L of copper sulfate, 0.01g/L of cobalt nitrate, 0.1g/L of zinc sulfate, 0.1g/L of manganese sulfate, 0.01g/L of molybdenum nitrate and 0.01g/L of ferrous sulfate; sterilizing at 121 deg.c and pH6.8 for 30min.
2. Primary seed tank culture:
inoculating the shake flask seed liquid into a culture medium of a 5L primary seed tank according to the inoculation amount of 3%, and culturing for 30 hours at 30 ℃ and tank pressure of 0.03Mpa and aeration ratio of 0.8 and stirring rotation speed of 250rpm to obtain the primary seed liquid in a logarithmic growth phase, wherein the primary seed liquid has good growth state.
The formula of the first-stage seed culture medium is as follows: glucose 2g/L, trisodium citrate 2g/L, monopotassium phosphate 1g/L, sodium chloride 0.5g/L, magnesium chloride 0.5g/L, ammonium sulfate 5g/L, monoammonium phosphate 1g/L, calcium chloride 0.1g/L, copper sulfate 0.01g/L, cobalt nitrate 0.01g/L, zinc sulfate 0.1g/L, manganese sulfate 0.1g/L, molybdenum nitrate 0.01g/L, and ferrous sulfate 0.01g/L; sterilizing at 121 deg.c and pH6.8 for 30min.
3. Culturing in a secondary seed tank:
inoculating the seed solution of the first-stage seed tank into the culture medium of a 100L second-stage seed tank according to the inoculation amount of 1%, and culturing for 24 hours at 30 ℃ under the tank pressure of 0.03Mpa with the aeration ratio of 0.8 and the stirring rotation speed of 250rpm to obtain the second-stage seed solution in the logarithmic phase, wherein the second-stage seed solution has good growth state.
The formula of the secondary seed culture medium is as follows: the concentration of glucose is 5g/L, the concentration of trisodium citrate is 3g/L, the concentration of potassium dihydrogen phosphate is 2g/L, the concentration of sodium chloride is 1g/L, the concentration of magnesium chloride is 0.5g/L, the concentration of ammonium dihydrogen phosphate is 7.5g/L, the concentration of calcium chloride is 0.5g/L, the concentration of copper sulfate is 0.05g/L, the concentration of cobalt nitrate is 0.05g/L, the concentration of zinc sulfate is 0.5g/L, the concentration of manganese sulfate is 0.3g/L, the concentration of molybdenum nitrate is 0.03g/L, and the concentration of ferrous sulfate is 0.02g/L. Sterilizing at 121 deg.c and pH6.8 for 30min.
4. Culturing in a fermentation tank:
the secondary seed liquid is inoculated into a 1000L fermentation tank according to 20 percent of inoculation amount, the aeration ratio is 0.8 at 30 ℃ and the tank pressure is 0.03MPa, the stirring speed is 150rpm, and the fermentation is stopped until the thalli start to rapidly decline.
The formula of the culture medium in the fermentation tank is as follows: 8.5g of sodium chloride, 2.0g of monopotassium phosphate, 7.2g of disodium phosphate, 0.5g of magnesium chloride, 0.1g of calcium chloride, 0.01g of ferrous sulfate, 0.01g of manganese sulfate, 0.005g of copper sulfate, 0.004g of boric acid, 0.003g of potassium manganate, 0.001g of ammonium molybdate, 0.4g of tyrosine, vitamin B1 (0.2 mg), vitamin B2 (2 mg), vitamin B6 (1 mg), vitamin B12 (0.05 mg), vitamin C (300 mg), vitamin E (2 mg) and biotin (0.05 mg); the pH was set at 7.0 and sterilized at 121℃for 30min.
The fermentation is carried out by the following feeding operation:
a) After 12 hours from the start of fermentation, the feeding of glucose carbon source was started with a mass fraction of 75% and a flow acceleration of 0.5%/h until the end time of fermentation was 120 hours. In the whole process, pure ammonia water is used for regulating the pH value, and the pH value is kept between 6.8 and 7.2.
b) After 30 hours from the start of fermentation, the feed mixture, including tryptophan, tyrosine, phenylalanine, methionine, monoammonium phosphate and vitamin B1, was fed in. Wherein, the concentration of tryptophan is 15g/L, the concentration of tyrosine is 40g/L, the concentration of phenylalanine is 30g/L, the concentration of methionine is 7.5g/L, the concentration of ammonium dihydrogen phosphate is 90g/L, and the concentration of vitamin B1 is 10g/L. The feed flow acceleration was 1%/h of the total fermentation volume, continuing until the end of the fermentation.
Results: the glucose consumption rate of the thalli is obviously reduced after 101h of fermentation tank culture, the thalli is partially autolyzed, the fermentation tank culture is stopped and the thalli is put into a tank, the coenzyme Q10 put into the tank with the titer of 4515mg/L and the dry weight of the thalli of 112g/L.
Example 2:
taking 200L of coenzyme Q10 as an example:
1. culturing fermentation seed liquid:
activating with beef extract peptone plate at 28deg.C for 2d, picking several colonies into shake flask culture medium, and culturing in shake flask at 28deg.C and rotation speed of 200rpm for 20 hr to obtain seed solution.
Wherein, beef extract peptone flat plate formula: 10g of beef extract, 8g of peptone and 1L of water, and regulating the pH to 7.0;
seed shake flask medium formula: 10g/L of peptone zymolyte, 8g/L of yeast extract powder, 2g/L of common meat extract, 5g/L of glucose, 3g/L of trisodium citrate, 3g/L of monopotassium phosphate, 1g/L of sodium chloride, 1g/L of magnesium chloride, 0.5g/L of calcium chloride, 0.05g/L of copper sulfate, 0.4g/L of cobalt nitrate, 0.5g/L of zinc sulfate, 0.3g/L of manganese sulfate and 0.2g/L of molybdenum nitrate. Final pH7.0, and sterilizing at 121deg.C for 30min.
2. Primary seed tank culture:
inoculating the shake flask seed liquid into a culture medium of a 5L primary seed tank according to the inoculation amount of 3%, and culturing for 30h at 28 ℃ and tank pressure of 0.03Mpa and aeration ratio of 0.8 and stirring rotation speed of 220rpm to obtain the primary seed liquid in the logarithmic phase, wherein the primary seed liquid has good growth state.
The formula of the first-stage seed culture medium is as follows: glucose 6g/L, trisodium citrate 3g/L, potassium dihydrogen phosphate 4g/L, sodium chloride 2g/L, magnesium chloride 1g/L, ammonium sulfate 8g/L, ammonium dihydrogen phosphate 2g/L, calcium chloride 1g/L, copper sulfate 0.2g/L, cobalt nitrate 0.5g/L, zinc sulfate 0.5g/L, manganese sulfate 0.3g/L, molybdenum nitrate 0.3g/L, and ferrous sulfate 0.2g/L; sterilizing at 121 deg.c and pH6.8 for 30min.
3. Culturing in a secondary seed tank:
inoculating the seed solution of the first-stage seed tank into the culture medium of a 20L second-stage seed tank according to the inoculum size of 5%, and culturing for 24 hours at 28 ℃ under the pressure of 0.04Mpa with the aeration ratio of 0.7 and the stirring rotation speed of 250rpm to obtain the second-stage seed solution in the logarithmic phase, wherein the second-stage seed solution has good growth state.
The formula of the secondary seed culture medium is as follows: there are 5g/L of glucose, 3g/L of trisodium citrate, 2g/L of potassium dihydrogen phosphate, 2g/L of sodium chloride, 1g/L of magnesium chloride, 8g/L of ammonium dihydrogen phosphate, 1g/L of calcium chloride, 0.1g/L of copper sulfate, 0.4g/L of cobalt nitrate, 0.3g/L of zinc sulfate, 0.2g/L of manganese sulfate, 0.2g/L of molybdenum nitrate and 0.1g/L of ferrous sulfate.
4. Culturing in a fermentation tank:
the secondary seed liquid is inoculated into a 200L fermentation tank according to 10 percent of inoculation amount, the aeration ratio is 0.75 at 28 ℃ and the tank pressure is 0.05MPa, the stirring speed is 180rpm, and the fermentation is stopped until the thalli start to rapidly descend.
The formula of the culture medium in the fermentation tank is as follows: 9g/L of sodium chloride, 5g/L of potassium dihydrogen phosphate, 8.5g/L of disodium hydrogen phosphate, 1.5g/L of magnesium chloride, 0.4g/L of calcium chloride, 0.02g/L of ferrous sulfate, 0.02g/L of manganese sulfate, 0.006g/L of copper sulfate, 0.008g/L of boric acid, 0.01g/L of potassium manganate, 0.003g/L of ammonium molybdate, 0.7g/L of tyrosine, 10.3mg/L of vitamin B, 22.5mg/L of vitamin B, 61.5mg/L of vitamin B, 120.3mg/L of vitamin B, 300mg/L of vitamin C, 2mg/L of vitamin E and 0.05mg/L of biotin. The pH was set at 7.0 and sterilized at 121℃for 30min.
The fermentation is carried out by the following feeding operation:
a) Glycerin at 75% concentration was fed in every hour from 13 hours at the beginning of fermentation, and the acceleration of the carbon source stream was controlled to be 0.5%/h until the fermentation was completed for 120 hours. In the whole process, pure ammonia water is used for adjusting the pH value to about 6.9.
b) In the fermentation process, mixed feed liquid is fed in every hour from the 30 th hour, wherein the tryptophan content is 12g/L, the tyrosine content is 40g/L, the phenylalanine content is 25g/L, the methionine content is 8g/L, the ammonium dihydrogen phosphate content is 90g/L, and the vitamin B1 content is 15g/L. The flow acceleration was 1%/h of the total fermentation volume.
Results: after 125h of fermentation in a fermentation tank, the glucose consumption rate of the thalli is obviously reduced, the thalli is partially autolyzed, the fermentation in the fermentation tank is stopped, the coenzyme Q10 is placed in the fermentation tank, the titer of the coenzyme Q10 placed in the fermentation tank is 4215mg/L, and the dry weight of the thalli is 98g/L.
Example 3
Taking the production of 20000L coenzyme Q10 as an example:
1. culturing fermentation seed liquid:
activating with beef extract peptone plate at 32deg.C for 4d, picking several colonies into shake flask culture medium, and culturing in shake flask at 32deg.C and 270rpm shaking table for 40 hr to obtain seed solution.
Wherein, beef extract peptone flat plate formula: 10g of beef extract, 8g of peptone and 1L of water, and regulating the pH to 7.0;
seed shake flask medium formula: 10g/L of peptone zymolyte, 6g/L of yeast extract powder, 2g/L of common meat extract, 6g/L of glucose, 3g/L of trisodium citrate, 3g/L of monopotassium phosphate, 1.5g/L of sodium chloride, 1.5g/L of magnesium chloride, 1g/L of calcium chloride, 0.05g/L of copper sulfate, 0.2g/L of cobalt nitrate, 0.5g/L of zinc sulfate, 0.2g/L of manganese sulfate, 0.15g/L of molybdenum nitrate and 0.1g/L of ferrous sulfate. The pH of the medium was adjusted to 7.0. Sterilizing at 121deg.C for 30min.
2. Primary seed tank culture:
inoculating the shake flask seed liquid into a culture medium of a 50L primary seed tank according to 10% of inoculation amount, and culturing for 30h at 28 ℃ under the tank pressure of 0.05Mpa with the aeration ratio of 0.9 and the stirring rotation speed of 220rpm to obtain the primary seed liquid in the logarithmic phase, wherein the primary seed liquid has good growth state.
The formula of the first-stage seed culture medium is as follows: glucose 6g/L, trisodium citrate 3g/L, monopotassium phosphate 4g/L, sodium chloride 2g/L, magnesium chloride 1g/L, ammonium sulfate 7.5g/L, monoammonium phosphate 3g/L, calcium chloride 1.5g/L, copper sulfate 0.03g/L, cobalt nitrate 0.2g/L, zinc sulfate 0.5g/L, manganese sulfate 0.3g/L, molybdenum nitrate 0.2g/L, and ferrous sulfate 0.15g/L. The pH of the medium was adjusted to 7.0. Sterilizing at 121deg.C for 30min.
3. Culturing in a secondary seed tank:
inoculating the seed solution of the first-stage seed tank into the culture medium of a 500L second-stage seed tank according to the inoculation amount of 5%, and culturing for 34 hours at 32 ℃ under the tank pressure of 0.05Mpa with the aeration ratio of 0.85 and the stirring rotation speed of 280rpm to obtain the second-stage seed solution in the logarithmic phase, wherein the second-stage seed solution has good growth state.
The formula of the secondary seed culture medium is as follows: the method comprises 5g/L of glucose, 3.5g/L of trisodium citrate, 3g/L of monopotassium phosphate, 2g/L of sodium chloride, 1.5g/L of magnesium chloride, 7.5g/L of monoammonium phosphate, 1g/L of calcium chloride, 0.03g/L of copper sulfate, 0.15g/L of cobalt nitrate, 0.4g/L of zinc sulfate, 0.25g/L of manganese sulfate, 0.15g/L of molybdenum nitrate and 0.1g/L of ferrous sulfate. The pH of the medium was adjusted to 7.0. Sterilizing at 121deg.C for 30min.
4. Culturing in a fermentation tank:
the secondary seed liquid is inoculated into a 20000L fermentation tank according to 10 percent of inoculation amount, the aeration ratio is 0.85 at 32 ℃ and the tank pressure is 0.05MPa, the stirring speed is 200rpm, and the fermentation is stopped until the thalli start to rapidly descend after the secondary seed liquid is cultured for 126 hours.
The formula of the culture medium in the fermentation tank is as follows: 9.5g/L of sodium chloride, 7.0g/L of potassium dihydrogen phosphate, 8.2g/L of disodium hydrogen phosphate, 1.0g/L of magnesium chloride, 0.3g/L of calcium chloride, 0.02g/L of ferrous sulfate, 0.02g/L of manganese sulfate, 0.008g/L of copper sulfate, 0.015g/L of boric acid, 0.025g/L of potassium manganate, 0.005g/L of ammonium molybdate, 0.6g/L of tyrosine, 10.3mg/L of vitamin B, 22.0mg/L of vitamin B, 61.5mg/L of vitamin B, 120.1mg/L of vitamin C, 300mg/L of vitamin E2.0mg/L and 0.03mg/L of biotin. The pH was set at 7.0 and sterilized at 121℃for 30min.
The fermentation is carried out by the following feeding operation:
a) The 70% glucose solution was fed at a concentration of 0.5%, and the feeding was started 12 hours after the start of fermentation, and the acceleration of the carbon source stream was controlled to be 1.5%/h and continued until 120 hours. In the feeding process, pure ammonia water is used to control the pH value to be about 6.8-7.2, and the stability is maintained.
b) The mixed feed liquid is fed in, and contains 15g/L tryptophan, 40g/L tyrosine, 30g/L phenylalanine, 7.5g/L methionine, 90g/L monoammonium phosphate and 110g/L vitamin B. Feeding was started 30 hours after the start of fermentation, with a flow rate of 1%/h of the total fermentation volume, and continued until the end of fermentation.
Results: after 116h of fermentation tank culture, the glucose consumption rate of the thalli is obviously reduced, the thalli is partially autolyzed, the fermentation tank culture is stopped and the byproducts are put into a tank, the put-into-tank titer of the coenzyme Q10 is 4915mg/L, and the dry weight of the thalli is 131g/L.
The present invention is not limited to the above-mentioned embodiments, and any changes or substitutions that can be easily understood by those skilled in the art within the technical scope of the present invention are intended to be included in the scope of the present invention.
Claims (10)
1. A coenzyme Q10 fermentation medium, characterized in that: the fermentation medium comprises the following raw materials in concentration: 8.5-10g/L of sodium chloride, 2.0-13g/L of potassium dihydrogen phosphate, 7.2-11.0g/L of disodium hydrogen phosphate, 0.5-2g/L of magnesium chloride, 0.1-0.6g/L of calcium chloride, 0.01-0.05g/L of ferrous sulfate, 0.01-0.04g/L of manganese sulfate, 0.005-0.01g/L of copper sulfate, 0.004-0.02g/L of boric acid, 0.003-0.04g/L of potassium manganate, 0.001-0.01g/L of ammonium molybdate, 0.4-1g/L of tyrosine, 10.2-0.5mg/L of vitamin B, 21-3mg/L of vitamin B, 61-2mg/L of vitamin B, 120.05-1mg/L of vitamin C, 100-500mg/L of vitamin E and 0.01-0.07mg/L of biotin.
2. A low cost, clean fermentation process for coenzyme Q10 comprising the steps of:
(1) Seed liquid culture: firstly, performing activation culture on a beef extract peptone flat plate, picking up bacterial colonies, placing the bacterial colonies into a shake flask culture medium, and performing shake flask culture to obtain shake flask seed liquid;
(2) Primary seed tank culture: inoculating the shake flask seed liquid into a culture medium of a first-stage seed tank according to an inoculum size of 1-5% for culture to obtain a first-stage seed liquid in a good growth state and a logarithmic growth phase;
(3) Culturing in a secondary seed tank: inoculating the primary seed liquid of the primary seed tank into a culture medium of the secondary seed tank according to the inoculation amount of 1-5% to culture, so as to obtain the secondary seed liquid in a good growth state and a logarithmic growth phase;
(4) Culturing in a fermentation tank: inoculating the secondary seed liquid into a fermentation tank according to 10-30% of inoculum size for culturing, and stopping fermentation when the thalli begin to rapidly descend;
in the fermentation tank, the coenzyme Q10 fermentation medium comprises the following raw materials with the concentration: 8.5-10g/L of sodium chloride, 2.0-13g/L of potassium dihydrogen phosphate, 7.2-11.0g/L of disodium hydrogen phosphate, 0.5-2g/L of magnesium chloride, 0.1-0.6g/L of calcium chloride, 0.01-0.05g/L of ferrous sulfate, 0.01-0.04g/L of manganese sulfate, 0.005-0.01g/L of copper sulfate, 0.004-0.02g/L of boric acid, 0.003-0.04g/L of potassium manganate, 0.001-0.01g/L of ammonium molybdate, 0.4-1g/L of tyrosine, 10.2-0.5mg/L of vitamin B, 21-3mg/L of vitamin B, 61-2mg/L of vitamin B, 120.05-1mg/L of vitamin C, 100-500mg/L of vitamin E and 0.01-0.07mg/L of biotin.
3. The low cost, clean fermentation process of coenzyme Q10 of claim 2, wherein in step (1) the beef extract peptone slab comprises the following concentrations of raw materials: 5-10g of beef extract, 6-10g of peptone, 1L of water and pH of 6.8-7.2; the shake flask culture medium comprises the following raw materials in concentration: 3-10g/L of peptone zymolyte, 5-12g/L of yeast extract powder, 1-3g/L of common meat extract, 2-10g/L of glucose, 2-5g/L of trisodium citrate, 1-5g/L of monopotassium phosphate, 0.5-3g/L of sodium chloride, 0.5-2g/L of magnesium chloride, 0.1-2g/L of calcium chloride, 0.01-0.5g/L of copper sulfate, 0.01-0.7g/L of cobalt nitrate, 0.1-0.9g/L of zinc sulfate, 0.1-0.5g/L of manganese sulfate, 0.01-0.4g/L of L molybdenum nitrate and 0.01-0.4g/L of ferrous sulfate; sterilizing at 121deg.C for 30min at pH 6.8-7.2.
4. The low-cost, clean fermentation process of coenzyme Q10 according to claim 2, wherein in step (1), the activation culture temperature is 28-32℃and the culture is carried out for 2-3 days; the culture temperature of the shake flask is 28-32 ℃, the rotating speed is 200-250rpm, and the culture is carried out for 12-24 hours.
5. The low cost, clean fermentation process of coenzyme Q10 according to claim 2, wherein in step (2) the medium of the primary seed tank comprises the following concentrations of raw materials: 2-10g/L of glucose, 2-5g/L of trisodium citrate, 1-5g/L of monopotassium phosphate, 0.5-3g/L of sodium chloride, 0.5-2g/L of magnesium chloride, 5-10g/L of ammonium sulfate, 1-5g/L of monoammonium phosphate, 0.1-2g/L of calcium chloride, 0.01-0.5g/L of copper sulfate, 0.01-0.7g/L of cobalt nitrate, 0.1-0.9g/L of zinc sulfate, 0.1-0.5g/L of manganese sulfate, 0.01-0.4g/L of molybdenum nitrate and 0.01-0.4g/L of ferrous sulfate; sterilizing at 121deg.C for 30min at pH of 6.8-7.2; the culture temperature of the first-stage seed tank is 28-32 ℃, the tank pressure is 0.02-0.05Mpa, the aeration ratio is 0.5-1.0, the stirring rotation speed is 200-300rpm, and the culture is carried out for 23-40h.
6. The low cost, clean fermentation process of coenzyme Q10 according to claim 2, wherein in step (3) the medium of the secondary seed tank comprises the following concentrations of raw materials: 2-10g/L of glucose, 2-5g/L of trisodium citrate, 1-5g/L of monopotassium phosphate, 0.5-3g/L of sodium chloride, 0.5-2g/L of magnesium chloride, 5-10g/L of monoammonium phosphate, 0.1-2g/L of calcium chloride, 0.01-0.5g/L of copper sulfate, 0.01-0.7g/L of cobalt nitrate, 0.1-0.9g/L of zinc sulfate, 0.1-0.5g/L of manganese sulfate, 0.01-0.4g/L of molybdenum nitrate and 0.01-0.4g/L of ferrous sulfate; sterilizing at 121deg.C for 30min at pH of 6.8-7.2; the culture temperature of the secondary seed tank is 28-32 ℃, the tank pressure is 0.02-0.05Mpa, the aeration ratio is 0.5-1.0, the stirring rotation speed is 200-300rpm, and the culture is carried out for 23-40h.
7. The low-cost, clean fermentation process of coenzyme Q10 according to claim 2, wherein in step (4), the fermentation tank culture temperature is 28-32 ℃, the tank pressure is 0.02-0.05MPa, the aeration ratio is 0.5-1.0, and the stirring rotation speed is 100-200rpm.
8. The low cost, clean fermentation process of coenzyme Q10 according to claim 2, further comprising the step of feeding a carbon source in step (4): glucose, sucrose or glycerol with the mass fraction of 70-80% is used as a carbon source, the carbon source is fed in from 12-15h after fermentation starts, the flow acceleration is 0.5%/h-1.5%/h of the total fermentation volume, the fermentation lasts for 100-130h, and the pH of the fermentation is controlled to be 6.8-7.2 by pure ammonia water during the fermentation, so that the fermentation is kept stable.
9. The low cost, clean fermentation process of coenzyme Q10 according to claim 2, further comprising the step of feeding the mixed feed solution in step (4): the method comprises the steps of feeding 10-20g/L tryptophan, 30-50g/L tyrosine, 20-40g/L phenylalanine, 5-10g/L methionine, 80-100g/L monoammonium phosphate and 15-20g/L vitamin B from 30 hours after fermentation starts, controlling the flow acceleration to be 1% of the total fermentation volume per hour, and continuing until the fermentation is finished.
10. A mixed feed supplement liquid for coenzyme Q10 fermentation is characterized in that: the mixed feed supplement liquid comprises the following raw materials in concentration: 10-20g/L tryptophan, 30-50g/L tyrosine, 20-40g/L phenylalanine, 5-10g/L methionine, 80-100g/L monoammonium phosphate and 15-20g/L vitamin B.
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