CN111154815A - Method for improving production efficiency of L-tryptophan - Google Patents
Method for improving production efficiency of L-tryptophan Download PDFInfo
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- CN111154815A CN111154815A CN202010086559.6A CN202010086559A CN111154815A CN 111154815 A CN111154815 A CN 111154815A CN 202010086559 A CN202010086559 A CN 202010086559A CN 111154815 A CN111154815 A CN 111154815A
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- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 title claims abstract description 106
- 229960004799 tryptophan Drugs 0.000 title claims abstract description 65
- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 24
- 238000000855 fermentation Methods 0.000 claims abstract description 110
- 230000004151 fermentation Effects 0.000 claims abstract description 110
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 6
- 239000002518 antifoaming agent Substances 0.000 claims abstract description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001963 growth medium Substances 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 241000588724 Escherichia coli Species 0.000 claims abstract 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 abstract description 5
- 235000015097 nutrients Nutrition 0.000 claims description 38
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 27
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 20
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 19
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 19
- 239000004202 carbamide Substances 0.000 claims description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- 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 14
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 14
- GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 claims description 14
- 239000008103 glucose Substances 0.000 claims description 14
- 229960005190 phenylalanine Drugs 0.000 claims description 13
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 12
- 239000002609 medium Substances 0.000 claims description 11
- 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 description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 10
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 10
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 9
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 9
- 229960000367 inositol Drugs 0.000 claims description 9
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 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 6
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 claims description 6
- 235000019743 Choline chloride Nutrition 0.000 claims description 6
- 229960003178 choline chloride Drugs 0.000 claims description 6
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 claims description 6
- 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
- 229960002685 biotin Drugs 0.000 claims description 5
- 235000020958 biotin Nutrition 0.000 claims description 5
- 239000011616 biotin Substances 0.000 claims description 5
- 229940041514 candida albicans extract Drugs 0.000 claims description 5
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 5
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 5
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 5
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 claims description 5
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 claims description 5
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 claims description 5
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 5
- 239000012138 yeast extract Substances 0.000 claims description 5
- 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
- 238000012258 culturing Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 229960001031 glucose Drugs 0.000 claims description 2
- 229940076263 indole Drugs 0.000 claims description 2
- 229960004441 tyrosine Drugs 0.000 claims description 2
- 238000011081 inoculation Methods 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 5
- 239000002054 inoculum Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 30
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 239000002253 acid Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 8
- -1 aromatic amino acid Chemical class 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000002503 metabolic effect Effects 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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- 108090000364 Ligases Proteins 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- FPWMCUPFBRFMLH-UHFFFAOYSA-N prephenic acid Chemical compound OC1C=CC(CC(=O)C(O)=O)(C(O)=O)C=C1 FPWMCUPFBRFMLH-UHFFFAOYSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
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- 241001465754 Metazoa Species 0.000 description 4
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
- 229910001429 cobalt ion Inorganic materials 0.000 description 4
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 4
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- 230000004907 flux Effects 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000001384 succinic acid Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010082495 Dietary Plant Proteins Proteins 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000003674 animal food additive Substances 0.000 description 2
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- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 2
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- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- 102000034263 Amino acid transporters Human genes 0.000 description 1
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- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
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- 229930182817 methionine Natural products 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
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- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940070527 tourmaline Drugs 0.000 description 1
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- 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
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
- C12P13/22—Tryptophan; Tyrosine; Phenylalanine; 3,4-Dihydroxyphenylalanine
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- 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 belongs to the technical field of L-tryptophan production, and discloses a method for improving the production efficiency of L-tryptophan, which comprises the steps of inoculating 5-12% of an inoculum size to an Escherichia coli seed liquid for producing L-tryptophan into a fermentation tank filled with a fermentation culture medium, wherein the culture temperature is 36-37 ℃, the dissolved oxygen is 20-30%, the pH value of a system in the tank is maintained at 6.8-7.2 by numerical control automatic fed-batch ammonia water, and defoaming agent is fed-batch for defoaming; the total fermentation time is 40-42h, and L-tryptophan fermentation liquor is obtained. The invention needs to further optimize the fermentation conditions on the basis of the prior art so as to improve the yield of the L-tryptophan.
Description
Technical Field
The invention belongs to the technical field of L-tryptophan production, and particularly relates to a method for improving the production efficiency of L-tryptophan.
Background
L-tryptophan has the molecular formula C11H12O2N2Molecular weight 204.21, nitrogen content 13.72%. L-tryptophan is neutral aromatic amino acid containing indolyl, has silky luster, hexagonal flaky self-color crystal, no odor, sweet taste, water solubility of 1.14g/L (25 deg.C), solubility in dilute acid or dilute alkali, stability in alkaline solution, decomposition in strong acid, slight solubility in ethanol, and insolubility in chloroform and diethyl ether.
L-tryptophan is one of eight essential amino acids in human and animal life activities, plays an important role in growth, development and metabolism of human and animals, and is called as a second essential amino acid. L-tryptophan plays an important role in the growth and development and life activities of human and animals, is second only to lysine, but cannot be synthesized in human and animal bodies, and must be taken in from the outside to meet physiological needs. In vivo, from L-tryptophan, bioactive substances such as 5-hydroxytryptamine, indoleacetic acid, nicotinic acid, pigment, alkaloid, coenzyme and the like can be synthesized. It is mainly used in medicine in clinic, and its content in nervous system is related to nervous excitement and inhibition state, so as to promote sleep and tranquilization, and can be used as health food and tranquilizer. L-tryptophan is also a relatively deficient amino acid in some vegetable proteins, and the enhancement of food and feed additives by using it has an important effect on improving the utilization rate of the vegetable proteins. It is the third largest feed additive amino acid after methionine and lysine. In addition, the L-tryptophan has the functions of preventing mildew, sterilizing and preventing oxidation, and can be used as a fish preservative.
The production of L-tryptophan goes through four development processes of protein hydrolysis, chemical synthesis, enzymatic conversion and microbial direct fermentation. With the development of modern biological science and technology, the organisms originally controlled by nature are gradually controllable, especially the proposal and application of gene recombination technology and metabolic engineering thought create a new opportunity for the production of L-tryptophan by a microorganism direct fermentation method. The method for producing amino acid by microorganism direct fermentation has the advantages of cheap raw materials, easy separation of products and the like and is widely concerned.
Since the metabolic flux of tryptophan in microorganisms is intricate, the synthesis thereof is subject to extremely strict enzyme regulation mechanisms, resulting in the restriction of metabolic flux to tryptophan, thereby making it difficult for tryptophan to accumulate in microorganisms. By analyzing the research mechanism of L-tryptophan biosynthesis, related genes are reasonably regulated and controlled on the basis, and metabolic flow is promoted to the synthesis of L-tryptophan. The L-tryptophan metabolism control mechanism comprises feedback inhibition and repression effects of various substrates or intermediates, and is accompanied with weakening effect of an operon, and diverse and complex cell control brings great challenges for the production of L-tryptophan directly by a microbial direct fermentation method. In recent years, the results of studies on amino acid transport systems have shown that the secretion rate of an intracellular target amino acid is increased while the absorption rate of an extracellular target amino acid is decreased, so that the intracellular target amino acid concentration is kept at a low level, and the synthesis of the target amino acid by bacterial cells is promoted. The amino acid transport system is divided into a secretion system and an absorption system, since genes have not been identified with respect to the L-tryptophan secretion system. The engineering strain constructed by the genetic engineering means can relieve the negative reaction feedback inhibition in the tryptophan synthesis process and enhance the expression of some key enzymes, but has new problems in the actual fermentation, such as the obvious reduction of the L-tryptophan synthesis rate in the middle and later stages of the fermentation, high sugar point requirement precision in the process control, the accumulation of metabolic byproducts such as acetic acid and the like.
The literature 'the influence of succinic acid on the L-tryptophan produced by fermentation of escherichia coli, 2017 communication of fermentation technology', experiments are carried out on a 30L fermentation tank, 1g/L of succinic acid is added along with sugar exogenous flow after 10 hours of fermentation so as to reduce the accumulation of metabolic inhibitor and improve the yield of L-tryptophan, and the results show that: compared with the fermentation without adding succinic acid, the fermentation with 1g/L added exogenous succinic acid increases the biomass of the thallus and the yield of L-tryptophan by 5.4 percent and 10 percent respectively, reduces the accumulated amount of acetic acid by 9.5 percent and increases the conversion rate of saccharic acid by 4.0 percent. The results show that the yield of L-tryptophan can be improved, the accumulation of acetic acid can be reduced, and the conversion rate of saccharic acid can be improved by adding 1g/L succinic acid through exogenous feeding for fermentation.
The applicant has made intensive studies on L-tryptophan fermentation, for example, "CN 201711289822" discloses a method of fermentation with a single strain, which increases fermentation acid production by adding tourmaline and using a dialysis medium; the method improves the fermentation acid yield, but needs to replace the culture medium, has higher operation difficulty and is easy to cause the death of partial strains. "CN 2018115428142" discloses a process for producing L-tryptophan by fermentation, wherein choline chloride is added into a fermentation medium, and a nutrient solution containing indole is fed-batch added in the middle stage of fermentation, so that the fermentation yield of tryptophan is improved and can reach 50g/L at most. On the basis of the prior art, further optimization of the fermentation conditions is required to improve the yield of L-tryptophan.
Disclosure of Invention
In order to solve the problems, the invention provides a method for improving the production efficiency of L-tryptophan.
The invention is realized by the following technical scheme.
A method for improving the production efficiency of L-tryptophan, which is characterized by comprising the following steps:
when the fermentation time is 12 hours, feeding the nutrient solution A into the fermentation tank until the fermentation is finished;
when the fermentation time is 24 hours, feeding the nutrient solution B into the fermentation tank until the fermentation is finished;
the component of the nutrient solution A comprises cobalt chloride hexahydrate;
the nutrient solution B comprises glucose, indole, inositol, phenylalanine and tyrosine.
Preferably, the components of the nutrient solution a include cobalt chloride hexahydrate and urea.
Preferably, the nutrient solution A comprises the following components: 10-30mg/L of cobalt chloride hexahydrate, 5-20g/L of urea and the balance of water.
Preferably, the nutrient solution B comprises the following components: 100g/L glucose, 1g/L indole, 0.5g/L inositol, 0.3-0.8g/L phenylalanine, 0.2-0.7g/L tyrosine, and the balance water.
More preferably, the nutrient solution A comprises the following components: 20mg/L of cobalt chloride hexahydrate, 10g/L of urea and the balance of water.
More preferably, the nutrient solution B comprises the following components: 100g/L glucose, 1g/L indole, 0.5g/L inositol, 0.5g/L phenylalanine, 0.4g/L tyrosine, and the balance water.
Specifically, the method comprises the following steps:
inoculating Escherichia coli seed liquid producing L-tryptophan with an inoculum size of 5-12% into a fermentation tank filled with fermentation culture medium, culturing at 36-37 deg.C with dissolved oxygen of 20-30%, maintaining the pH of the system in the tank at 6.8-7.2 by numerical control automatic feeding ammonia water, and defoaming by feeding defoaming agent; the total fermentation time is 40-42h, and L-tryptophan fermentation liquor is obtained;
when the fermentation time is 12 hours, feeding the nutrient solution A into the fermentation tank, wherein the feeding speed is 0.005-0.015ml/min per L of fermentation solution until the fermentation is finished;
when the fermentation time is 24 hours, feeding the nutrient solution B into the fermentation tank, and maintaining the sugar concentration in the tank to be 0.8-1.5g/L until the fermentation is finished.
Preferably, the components of the fermentation medium are: 20g/L of glucose, 9g/L of dipotassium phosphate, 5g/L of yeast extract, 4.6g/L of citric acid, 1.8g/L of ammonium sulfate, 1.6g/L of magnesium sulfate heptahydrate, 0.4g/L of choline chloride, 65mg/L of ferrous sulfate heptahydrate and 0.2mg/L of biotin.
The technical scheme of the invention has the following outstanding advantages and uniqueness:
the invention starts from the pathway of synthesizing aromatic amino acid by escherichia coli, adopts various modes to regulate metabolic pathways, and improves the yield and acid production rate of tryptophan by mutual synergy;
according to the invention, phenylalanine and tyrosine are added in the middle stage of fermentation, and the yield of aromatic amino acid is in the process of rapid accumulation, so that the feedback inhibition effect on the conversion of the mycolic acid to the prephenate is generated, and the mycolic acid flows to the anthranilic acid way more, so that the yield of tryptophan is increased;
compared with other metal ions, cobalt ions have a larger influence on the conformation of the DAHP synthetase and can be used as an enzyme activator.
The urea is added at the initial stage of fermentation, is mainly used as an inorganic nitrogen source for the proliferation of the strain, does not influence the activity of the DAHP synthetase, and is slowly proliferated when the fermentation is carried out for 12 hours, so that the activity of the DAHP synthetase can be improved by mainly using synthetic metabolites, the metabolic flux of an aromatic amino acid synthetic pathway is promoted to be increased, and the yield of tryptophan is promoted to be increased.
Drawings
FIG. 1: the effect of phenylalanine and tyrosine on tryptophan production;
FIG. 2: the influence of phenylalanine and tyrosine on the fermentation acid production rate;
FIG. 3: the effect of cobalt chloride hexahydrate concentration on tryptophan yield;
FIG. 4: influence of urea concentration on tryptophan production.
Detailed Description
Those skilled in the art can modify the process parameters appropriately to achieve the desired results with reference to the disclosure herein. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the products and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations and modifications, or appropriate alterations and combinations, of the products and methods described herein may be made and utilized without departing from the spirit, scope, and spirit of the invention. For a further understanding of the present invention, reference will now be made in detail to the following examples.
Example 1
A method for improving the production efficiency of L-tryptophan comprises the following steps:
the fermentation medium comprises the following components: 20g/L of glucose, 9g/L of dipotassium phosphate, 5g/L of yeast extract, 4.6g/L of citric acid, 1.8g/L of ammonium sulfate, 1.6g/L of magnesium sulfate heptahydrate, 0.4g/L of choline chloride, 65mg/L of ferrous sulfate heptahydrate and 0.2mg/L of biotin; the nutrient solution A comprises the following components: 20mg/L of cobalt chloride hexahydrate and 10g/L of urea;
the nutrient solution B comprises the following components: 100g/L glucose, 1g/L indole, 0.5g/L inositol, 0.5g/L phenylalanine, 0.4g/L tyrosine;
coli TRTH, the seed liquid (OD) was inoculated at 8%600Value of 11.2) is inoculated into a 1000L fermentation tank filled with 600L fermentation medium, the culture temperature is 36.8 ℃, the dissolved oxygen is 20 percent, the pH value of the system in the tank is maintained between 7.0 and 7.2 by numerical control automatic feeding of 25 percent ammonia water, and defoaming is carried out by feeding defoaming agent; the total fermentation time is 42h, and L-tryptophan fermentation liquor is obtained.
When the fermentation time is 12 hours, feeding the nutrient solution A into the fermentation tank, wherein the feeding speed is 0.01ml/min per L of fermentation solution until the fermentation is finished;
when the fermentation time is 24 hours, the nutrient solution B is fed into the tank, and the sugar concentration in the tank is maintained to be 1g/L until the fermentation is finished.
Example 2
A method for improving the production efficiency of L-tryptophan comprises the following steps:
the fermentation medium comprises the following components: 20g/L of glucose, 9g/L of dipotassium phosphate, 5g/L of yeast extract, 4.6g/L of citric acid, 1.8g/L of ammonium sulfate, 1.6g/L of magnesium sulfate heptahydrate, 0.4g/L of choline chloride, 65mg/L of ferrous sulfate heptahydrate and 0.2mg/L of biotin;
the nutrient solution A comprises the following components: 30mg/L of cobalt chloride hexahydrate and 15g/L of urea;
the nutrient solution B comprises the following components: 100g/L glucose, 1g/L indole, 0.5g/L inositol, 0.4g/L phenylalanine, 0.3g/L tyrosine;
coli TRTH, the seed liquid (OD) was inoculated at 8%600Value of 11.8) is inoculated into a 1000L fermentation tank filled with 600L fermentation medium, the culture temperature is 36.8 ℃, the dissolved oxygen is 20 percent, the pH value of the system in the tank is maintained between 7.0 and 7.2 by numerical control automatic feeding of 25 percent ammonia water, and defoaming is carried out by feeding defoaming agent; the total fermentation time is 40h, and the L-tryptophan fermentation liquor is obtained.
When the fermentation time is 12 hours, feeding the nutrient solution A into the fermentation tank, wherein the feeding speed is 0.008ml/min per L of fermentation solution until the fermentation is finished;
when the fermentation time is 24 hours, the nutrient solution B is fed into the tank, and the sugar concentration in the tank is maintained to be 1g/L until the fermentation is finished.
Comparative example 1
A method for improving the production efficiency of L-tryptophan comprises the following steps:
the fermentation medium comprises the following components: 20g/L of glucose, 9g/L of dipotassium phosphate, 5g/L of yeast extract, 4.6g/L of citric acid, 1.8g/L of ammonium sulfate, 1.6g/L of magnesium sulfate heptahydrate, 0.4g/L of choline chloride, 65mg/L of ferrous sulfate heptahydrate and 0.2mg/L of biotin;
the nutrient solution comprises the following components: 100g/L glucose, 1g/L indole and 0.5g/L inositol;
coli TRTH, the seed liquid (OD) was inoculated at 8%600Value of 11.2) is inoculated into a 1000L fermentation tank filled with 600L fermentation medium, the culture temperature is 36.8 ℃, the dissolved oxygen is 20 percent, the pH value of the system in the tank is maintained between 7.0 and 7.2 by numerical control automatic feeding of 25 percent ammonia water, and defoaming is carried out by feeding defoaming agent; the total fermentation time is 42h, and L-tryptophan fermentation liquor is obtained.
When the fermentation time is 24 hours, nutrient solution flow is added into the tank, and the sugar concentration in the tank is maintained to be 1g/L until the fermentation is finished.
Example 3
The research is carried out on the basis of the prior research result compared with the document 1.
The influence of phenylalanine and tyrosine on the yield of tryptophan and the fermentation acid production rate is verified, and the method 1: adding phenylalanine 0.5g/L and tyrosine 0.4g/L into a fermentation culture medium; mode 2: adding 0.5g/L phenylalanine and 0.4g/L tyrosine into the nutrient solution; as shown in figure 1, in the mode 2, phenylalanine and tyrosine are added into the nutrient solution, the yield of tryptophan and the fermentation acid production rate are both higher than those in the mode 1, the nutrient solution is added in the middle stage of fermentation, at the moment, the yield of aromatic amino acid is in the process of rapid accumulation, and feedback inhibition effect is generated on the conversion of the mycolic acid into the prephenate by adding the phenylalanine and the tyrosine, so that the mycolic acid flows to the anthranilic acid pathway more, and the yield of the tryptophan is improved; the mode 1 is added into a fermentation culture medium, so that the accumulation of aromatic amino acids is less in the early stage of fermentation, the feedback inhibition of phenylalanine and tyrosine on the conversion of mycolic acid into prephenate is not started, and the phenylalanine and tyrosine are added to be absorbed and utilized by bacterial cells at the moment, and the positive regulation effect on tryptophan synthesis is not obvious.
On the basis of the research, phenylalanine and tyrosine are added into the nutrient solution B; further discussing the influence of cobalt chloride hexahydrate on the yield of tryptophan; the research shows that the addition of cobalt ions in the initial fermentation stage has limited influence on the activity of the DAHP synthetase, the yield of tryptophan cannot be improved, the initial fermentation stage is possible, the aromatic amino acid synthesis pathway is not started, and the enzyme secretion amount is relatively small; therefore, the cobalt ions are added at the time point of mass synthesis of tryptophan, considering that the addition of an overlarge amount of nutrient solution can cause dilution effect on the fermentation liquor, the flow rate is set to be 0.01ml/min per L of the fermentation liquor, and the concentration is set to be 1,2.5,5,10,20,30,40,60 and 80 (mg/L) respectively at the flow rate; as shown in FIG. 3, the yield of tryptophan is improved with the increase of the concentration of cobalt chloride hexahydrate, the influence on tryptophan is the greatest when the concentration is 20-30mg/L, the increase of the concentration is not obviously changed, the yield of tryptophan is reduced to some extent when the concentration is more than 60mg/L, and the growth of the strain is possibly inhibited by excessive cobalt ions.
Selecting the concentration of cobalt chloride hexahydrate to be 20mg/L, and when the adding time is to ferment for 12 hours, the feeding speed is 0.01ml/min per L of fermentation liquor; the applicant tries to add urea into a fermentation medium, which has no obvious influence on the yield of tryptophan, and the urea is added in the initial stage of fermentation, mainly used as an inorganic nitrogen source for strain proliferation and does not influence the activity of DAHP synthetase, and when the fermentation is carried out for 12 hours, the strain proliferation is slowed, and at the moment, mainly used as an anabolite, the urea is added, so that the activity of the DAHP synthetase can be improved, the metabolic flux of an aromatic amino acid synthetic pathway is increased, the yield of tryptophan is increased, and the concentrations of the urea are respectively set to be 1,5,10,15,20,25 and 30 (g/L); as shown in FIG. 4, tryptophan production increased all the more with increasing urea concentration, with a 10g/L increase followed by a slower increase and then a plateau.
While the invention has been described with reference to specific embodiments, it will be apparent to those skilled in the art that the invention is not limited thereto, and that various changes and modifications can be made without departing from the spirit and scope of the invention.
Claims (10)
1. A method for improving the production efficiency of L-tryptophan, which is characterized by comprising the following steps:
when the fermentation time is 12 hours, feeding the nutrient solution A into the fermentation tank until the fermentation is finished;
when the fermentation time is 24 hours, feeding the nutrient solution B into the fermentation tank until the fermentation is finished;
the component of the nutrient solution A comprises cobalt chloride hexahydrate;
the nutrient solution B comprises glucose, indole, inositol, phenylalanine and tyrosine.
2. The method of claim 1 wherein the components of nutrient solution a include cobalt chloride hexahydrate and urea.
3. The method according to claim 1 or 2, characterized in that the nutrient solution a has the following components: 10-30mg/L of cobalt chloride hexahydrate, 5-20g/L of urea and the balance of water.
4. The method according to claim 1 or 2, wherein the nutrient solution B comprises the following components: 100g/L glucose, 1g/L indole, 0.5g/L inositol, 0.3-0.8g/L phenylalanine, 0.2-0.7g/L tyrosine, and the balance water.
5. The method according to claim 3, wherein the nutrient solution A comprises the following components: 20mg/L of cobalt chloride hexahydrate, 10g/L of urea and the balance of water.
6. The method according to claim 4, wherein the nutrient solution B comprises the following components: 100g/L glucose, 1g/L indole, 0.5g/L inositol, 0.5g/L phenylalanine, 0.4g/L tyrosine, and the balance water.
7. Method according to claim 5 or 6, characterized in that it comprises the following steps:
inoculating Escherichia coli seed solution capable of producing L-tryptophan into a fermentation tank filled with fermentation culture medium at an inoculation amount of 5-12%, culturing at 36-37 deg.C with dissolved oxygen of 20-30%, maintaining system pH at 6.8-7.2 by adding ammonia water, and defoaming by adding defoaming agent; the total fermentation time is 40-42h, and L-tryptophan fermentation liquor is obtained;
when the fermentation time is 12 hours, feeding the nutrient solution A into the fermentation tank, wherein the feeding speed is 0.005-0.015ml/min per L of fermentation solution until the fermentation is finished;
when the fermentation time is 24 hours, feeding the nutrient solution B into the fermentation tank, and maintaining the sugar concentration in the tank to be 0.8-1.5g/L until the fermentation is finished.
8. The method of claim 7, wherein the fermentation medium comprises: 20g/L of glucose, 9g/L of dipotassium phosphate, 5g/L of yeast extract, 4.6g/L of citric acid, 1.8g/L of ammonium sulfate, 1.6g/L of magnesium sulfate heptahydrate, 0.4g/L of choline chloride, 65mg/L of ferrous sulfate heptahydrate and 0.2mg/L of biotin.
9. An L-tryptophan product obtained by the method according to claims 1 to 8.
10. The L-tryptophan product according to claim 9 for use in medicine or food.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59192096A (en) * | 1983-04-13 | 1984-10-31 | Ajinomoto Co Inc | Preparation of l-tryptophan by fermentation |
| CN102978252A (en) * | 2011-09-02 | 2013-03-20 | 孟州市华兴生物化工有限责任公司 | L-tryptophan fed-batch fermentation technology |
| CN104388330A (en) * | 2014-09-26 | 2015-03-04 | 廊坊梅花生物技术开发有限公司 | L-tryptophan fermentation strain and method for fermentation production of L-tryptophan by using L-tryptophan fermentation strain |
| CN104694612A (en) * | 2015-02-12 | 2015-06-10 | 新疆阜丰生物科技有限公司 | Method for highly producing L-tryptophan employing industrial fermentation |
| CN109593801A (en) * | 2018-12-17 | 2019-04-09 | 新疆阜丰生物科技有限公司 | A kind of technique of fermenting and producing L-Trp |
| CN111139273A (en) * | 2019-12-17 | 2020-05-12 | 新疆阜丰生物科技有限公司 | Method for preparing, separating and extracting L-tryptophan |
-
2020
- 2020-02-11 CN CN202010086559.6A patent/CN111154815B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59192096A (en) * | 1983-04-13 | 1984-10-31 | Ajinomoto Co Inc | Preparation of l-tryptophan by fermentation |
| CN102978252A (en) * | 2011-09-02 | 2013-03-20 | 孟州市华兴生物化工有限责任公司 | L-tryptophan fed-batch fermentation technology |
| CN104388330A (en) * | 2014-09-26 | 2015-03-04 | 廊坊梅花生物技术开发有限公司 | L-tryptophan fermentation strain and method for fermentation production of L-tryptophan by using L-tryptophan fermentation strain |
| CN104694612A (en) * | 2015-02-12 | 2015-06-10 | 新疆阜丰生物科技有限公司 | Method for highly producing L-tryptophan employing industrial fermentation |
| CN109593801A (en) * | 2018-12-17 | 2019-04-09 | 新疆阜丰生物科技有限公司 | A kind of technique of fermenting and producing L-Trp |
| CN111139273A (en) * | 2019-12-17 | 2020-05-12 | 新疆阜丰生物科技有限公司 | Method for preparing, separating and extracting L-tryptophan |
Non-Patent Citations (2)
| Title |
|---|
| GAINES 等: "L-tyrosine regulation and biosynthesis via arogenate dehydrogenase in suspension-cultured cells of Nicotiana silvestris Speg. et Comes", 《PLANTA》 * |
| 杨海军: "不同添加物对L-色氨酸补料分批发酵的影响", 《天津科技大学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111139273A (en) * | 2019-12-17 | 2020-05-12 | 新疆阜丰生物科技有限公司 | Method for preparing, separating and extracting L-tryptophan |
| CN111139273B (en) * | 2019-12-17 | 2021-12-07 | 新疆阜丰生物科技有限公司 | Method for preparing, separating and extracting L-tryptophan |
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