CN102732416A - Airlift type loop reactor and method for penicillin fermentation by using the same - Google Patents

Airlift type loop reactor and method for penicillin fermentation by using the same Download PDF

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Publication number
CN102732416A
CN102732416A CN2012102015619A CN201210201561A CN102732416A CN 102732416 A CN102732416 A CN 102732416A CN 2012102015619 A CN2012102015619 A CN 2012102015619A CN 201210201561 A CN201210201561 A CN 201210201561A CN 102732416 A CN102732416 A CN 102732416A
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fermentation
ratio
circulating reactor
guide shell
penicillin
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刘振涛
盖来兵
周天舒
乔文庆
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Zhongrun (inner Mongolia) Co Ltd Shijiazhuang Pharmaceutical Group
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Zhongrun (inner Mongolia) Co Ltd Shijiazhuang Pharmaceutical Group
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/18Flow directing inserts
    • C12M27/24Draft tube
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/06Nozzles; Sprayers; Spargers; Diffusers
    • C12M29/08Air lift
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M45/00Means for pre-treatment of biological substances
    • C12M45/04Phase separators; Separation of non fermentable material; Fractionation

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Abstract

The present invention discloses an airlift type loop reactor and a method for penicillin fermentation by using the airlift type loop reactor. The lower part of the tower body of the airlift type loop reactor is the reaction section, and the upper part is the expanded gas-liquid separation section, wherein a height ratio of the gas-liquid separation section to the reaction section is 0.15-0.25, a diameter ratio is 1.25-1.42, a ratio of the total height of the tower body to the inner diameter of the reaction section is 4.5-8, a ratio of the inner diameter of a draft tube to the inner diameter of the tower body is 0.5-0.78, and a height ratio of the draft tube to the reaction section is 0.9-0.65. In the airlift type loop reactor, air is introduced, and a strain producing penicillium chrysogenum is adopted to produce penicillin, wherein the fermentation temperature is 20-30 DEG C, the pH value is 6.0-7.0, the fermentation pressure is 0.08-0.1 MPa, the ventilation ratio is controlled to 0.8-3 vvm, and the fermentation time is 160-170 hours.

Description

A kind of Airlift circulating reactor and utilize it to carry out the method for penicillin fermentation
Technical field
The present invention relates to a kind ofly be used for the reactor drum of penicillin fermentation and utilize this reactor drum to carry out the method for penicillin fermentation, particularly relate to a kind of Airlift circulating reactor and utilize Airlift circulating reactor to carry out the method for penicillin fermentation.
Background technology
The aerobic fermentation of the thread fungus system of HV non-Newtonian fluid, the typical case is like penicillin fermentation, and general the employing has churned mechanically pot type fermentation reactor; Produce under the condition of bubbling air, mechanical stirring makes being distributed in the tank body of even air, with the needs of the growth metabolism that guarantees thalline; But there are two important problem in this method: on the one hand, the energy consumption of agitator motor and compressed-air actuated energy consumption make the energy consumption of fermenting process generally higher, and general power consumption accounts for the 30-50% of cost; In penicillin fermentation is produced; Adopt the mechanical agitation type fermentor tank to ferment, power consumption average out to 20~25Kwh/BOU (BOU penicillium mould activity unit, down together); On the other hand, churned mechanically shearing force constitutes influence to the silk thalli growth equally.Penicillin fermentation belongs to second order fermentation, is divided into the penicillium spp growth and breeding and produces anti-two stages; In first stage of fermentation of penicillium mould, mechanical shearing is favourable, and it can promote mycelial vegetative propagation; But produce the anti-stage in the later stage, mechanical shearing has quickened mycelial self-dissolving, and then influences the penicillium mould biosynthesizing, and is unfavorable for the processing of downstream production process.In addition, there is shortcomings such as being prone to microbiological contamination, maintenance cost height in mechanical stir-reactor.
The exploitation of non-stirring-type fermentation reactor is the developing direction of fermentation reactor always, and Airlift circulating reactor is the fermentation reactor that wherein is hopeful most to replace stirred reactor.Airlift circulating reactor utilizes the inside and outside gas-liquid density difference of reactor drum inner draft tube to be impellent, and produces the guide shell circulation that centers on, and is one type of efficient solution-air; Gas-liquid-solid or solution-air-liquid heterophase reactor; It is simple in structure, and mass-transfer performance is good, and energy consumption is lower; Be easy to engineering and amplify, in chemical industry, petroleum industry, environmental engineering, biochemical engineering and other commercial run, have a wide range of applications.
At present, both at home and abroad be applied to low-viscosity newton or intend the research that the fermenting process of Newtonian fuid is widely used at Airlift circulating reactor, typical in citric acid fermentation; 100m 3And 250m 3Adopt the gas lift cyclic part to substitute the semi-air-lift formula fermentor tank application in the citric acid fermentation process of stirring, can make total power consumption practice thrift 30~40%.In gas lift type common loop reactor, directly cultivate the Penicllium chrysogenum bacterial strain and ferment correlation technique then do not appear in the newspapers.
The major cause that Airlift circulating reactor is difficult to be applied to penicillin fermentation is:
(1) because the circulation impellent of Airlift circulating reactor (density difference of the inside and outside gas-liquid of guide shell) is less, often do not reach the needs to dissolved oxygen of fermenting process; Perhaps need excessive gas speed to keep circulation, make the economy decline of process and make reactor drum be difficult to operation.
(2) hydrodynamic shear of Airlift circulating reactor is little, and in the elementary metabolism stage, under the situation of competent gas and nutritive substance supply, if extraneous shearing force is little, penicillium spp is prone to clump together, and is unfavorable at the product in secondary metabolism stage anti-at penicillium spp.
Summary of the invention
First purpose of the present invention is exploitation and proposes a kind of gas lift type common loop reactor that is used for penicillin fermentation.
Second purpose of the present invention is to provide a kind of method of utilizing gas lift type common loop reactor to carry out penicillin fermentation, to reduce the energy consumption of process, improves fermentation efficiency.
First purpose of the present invention is implemented by following technical scheme, a kind of gas lift type common loop reactor that is used for penicillin fermentation, it comprise tower body, with the coaxial mounted guide shell of tower body, gas distributor; Wherein guide shell is a single hop or multistage, it is characterized in that, the tower body bottom of said Airlift circulating reactor is a conversion zone; The gas-liquid separation section of top for enlarging; The aspect ratio of gas-liquid separation section and conversion zone is 0.15~0.25, and the diameter ratio is 1.25~1.42, and the tower body height overall is 4.5~8 with the ratio of conversion zone internal diameter; Guide shell internal diameter and conversion zone internal diameter ratio are 0.5~0.78, and guide shell height and conversion zone aspect ratio are 0.9~0.65.
The bottom of going up of said guide shell is the jagged edges that is made up of vee, the degree of depth 10~20mm of each breach, width 10~20mm, distance 5~15mm between breach.
The design of air-distributor guarantees that air edge and axial angle are 30 °~60 ° conical surface ejection, and egress line speed is not less than 2m/s.
Second purpose of the present invention is to provide a kind of method of utilizing Airlift circulating reactor to carry out penicillin fermentation, after Penicllium chrysogenum bacterial strain seed culture is accomplished, begins fermentation in the inoculum size access Airlift circulating reactor according to 8~10% (v/v).Leavening temperature is 20~30 ℃; PH is 6.0~7.0; The ventilation of fermentation whole process is than being controlled at 0.8~3vvm, and through regulating the ventilation ratio, the control dissolved oxygen is more than 30%; Fermentation pressure is 0.08~0.1Mpa; Fermentation period is 160~170h; Whole fermentation process control fermented liquid mycelial concentration is 35~45%.
Fermenting process need be added carbon source, nitrogenous source and precursor, and it is glucose that stream adds carbon source, and glucose concn is controlled at 70~85% (v/v), and glucose stream dosage is 1~2L/h; It is ammonium sulfate that stream adds nitrogenous source, and the concentration of ammonium sulfate is controlled at 30~40% (v/v), and the ammonium sulfate stream dosage is 0.1~0.2L/h; It is toluylic acid that stream adds precursor substance, and toluylic acid concentration is controlled at 30~40% (v/v), and toluylic acid stream dosage is 0.1~0.2L/h.
The present invention realizes above-mentioned target from the angle of optimizing structure of reactor, adjustment and optimization for fermentation technology parameter, the invention has the advantages that
(1) gas-liquid separation section diameter can spread greater than other gases that make to producing in reactant gases and the fermenting process that relate to of conversion zone diameter rapidly; Guarantee the good operation of reaction; The design of guide shell breach and gas distributor and help increasing a certain amount of shearing force overcomes problems such as penicillium spp is prone to clump together.
(3) utilize the Airlift multi-stage loop reactor drum to carry out penicillin fermentation, fermentation efficiency is higher than the fermentation of mechanical agitation type fermentor tank, and fermentation period can be from shortening about 20%, and fermentation unit can improve more than 10%;
(4) with respect to the mechanical type fermentor tank, fermenting process is little to mycelial shearing force, and the ratio of mycelium self-dissolving is little, can not cause difficulty for the processing of postorder;
(5) the power consumption average out to 20~25Kwh/BOU of mechanical agitating fermentation tank utilizes loop reactor to carry out the penicillium spp fermentation, and power consumption average out to 10~21Kwh/BOU in the fermenting process only is equivalent to 50% of tool stirred fermentor power consumption loss.
(6) because there are not utility appliance such as shaft coupling and the bearing of mechanical agitation type fermentor tank in the Airlift multi-stage loop reactor drum, greatly reduce the microbiological contamination rate.
The accompanying drawing summary description
Accompanying drawing 1 has shown Airlift circulating reactor of the present invention
Accompanying drawing 2 has shown the breach design of guide shell in the Airlift circulating reactor
Accompanying drawing 3 has shown a kind of design of gas distributor in the Airlift circulating reactor
Accompanying drawing 4 has shown the concrete design that is used to flow the Airlift circulating reactor that adds fermentation
Embodiment
Embodiment 1
Airlift circulating reactor
Explanation for each parts among the accompanying drawing 1-4 is following:
The 1-conversion zone, 2-gas-liquid separation section, 3-reactor head, 4-reactor drum bottom (head), 5-heat exchange jacket, 6-guide shell; The perforate of 7-guide shell, 8-opening for feed, 9-recirculated water inlet, 10-circulating water outlet, 11-visor liquidometer; Locating support on the 2-guide shell, 13-gas distributor, 14-guide shell lower bracket, 15-inlet pipe, 16-discharge gate; 17-stream adds mouth, and 18-stream adds a mouthful steam protection, 19-venting port, 20-SV, the design of 21-breach
The present invention has made concrete improvement to the design between each parts of Airlift circulating reactor, and is consistent with general Airlift circulating reactor for the concrete operation of retort.
Embodiment 2
A kind of 200L of utilization Airlift circulating reactor carries out the method for penicillin fermentation, after seed culture is accomplished, begins fermentation in the inoculum size access gas lift type common loop reactor according to 8~10% (v/v).Leavening temperature is 26 ℃; PH is 6.5 ± 0.1; The fermenting process ventilation is than 2.8vvm, and the control dissolved oxygen is more than 30%; Fermentation pressure is 0.1Mpa; Fermentation period is 165h; Whole fermentation process control fermented liquid mycelial concentration is about 40%.
Utilize the 200L Airlift circulating reactor to carry out in the penicillin fermentation process, adding carbon source is glucose, and glucose concn is 83% (w/v), and operation process glucose additional amount is 1.8L/h; Adding nitrogenous source is ammonium sulfate, and the concentration of ammonium sulfate is 37% (w/v), and operation process ammonium sulfate additional amount is 0.19L/h; Adding precursor substance is toluylic acid, and toluylic acid concentration is 36% (w/v), and operation process toluylic acid additional amount is 0.19L/h.Fermentation is put tank volume 152L after stopping; Microscopy mycelia complete form, self-dissolving is less; Fermented liquid is through vacuum filtration, and filtering velocity is 1.70mL/s, and obtaining penicillin fermentation unit is 106880u/mL.
Embodiment 3
Utilize 200L mechanical agitation type fermentor tank to compare experiment.After seed culture is accomplished, begin fermentation in the inoculum size access stirred-tank fermenter according to 8~10% (v/v).Leavening temperature is 25 ℃; PH is 6.4 ± 0.1; Mixing speed 380r/min; The fermenting process ventilation is than 1.3vvm, and the control dissolved oxygen is more than 30%; Fermentation pressure is 0.08Mpa; Fermentation period is 192h; Whole fermentation process control fermented liquid mycelial concentration is about 40%.Utilize 200L mechanical agitation type fermentor tank to carry out in the penicillin fermentation process, adding carbon source is glucose, and glucose concn is 83% (w/v), and operation process glucose additional amount is 1.7L/h; Adding nitrogenous source is ammonium sulfate, and the concentration of ammonium sulfate is 36% (w/v), and operation process ammonium sulfate additional amount is 0.21L/h; Adding precursor substance is toluylic acid, and toluylic acid concentration is 36% (w/v), and operation process toluylic acid additional amount is 0.20L/h.Fermentation is put tank volume 155L after stopping; The most mycelia fractures of microscopy, fragmentation, self-dissolving is more, and fermented liquid is through vacuum filtration, and filtering velocity is 1.32mL/s, and obtaining penicillin fermentation unit is 98643u/mL.
Embodiment 4
According to embodiment 2 embodiments, to 10 batches of Airlift circulating reactor continuous operation.After fermentation stopped, microscopy mycelia form was intact; Average filtration speed 1.73mL/s; The average fermentation cycle is 163h; Obtaining penicillium mould average fermentation unit is 106320u/mL.
Press embodiment 3 embodiments, to 10 batches of 200L mechanical agitation type fermentor tank continuous operation.After fermentation stops, the most mycelia fractures of microscopy, fragmentation, self-dissolving is more; Average rate of filtering is 1.20mL/s; The average fermentation cycle is 192h; Obtaining penicillium mould average fermentation unit is 96810u/mL.In the fermentation operation process, stir running power average out to 0.75Kwh.
Through above embodiment contrast, utilize gas lift type common loop reactor to carry out penicillin fermentation, fermentation period can shorten 15%; Fermentation unit can improve about 10%; Fermentation equipment is little to mycelial shearing force, and mycelial self-dissolving ratio is little; Fermented liquid suction filtration speed has improved more than 40%; Saved mechanical stirring, the power cost in the fermenting process significantly reduces.
Embodiment 6
Be the better penicillin fermentation effect that obtains, the parameter sectional of fermenting process of the present invention is controlled: after ferment-seeded is cultivated mycelial concentration to 20~40% (v/v), change Airlift circulating reactor over to and begin fermentation, fermentating liquid volume 168L.Leavening temperature is 25 ℃, and pressure is 0.08Mpa.Whole fermentation period 170h, preceding 0~60h air flow 8.5m 3/ h (the mark condition is equivalent to empty tower gas velocity 4cm/s), ventilation is than being 0.84vvm; Back 60~90h air flow 13m 3/ h (the mark condition is equivalent to empty tower gas velocity 6cm/s), ventilation is than being 1.29vvm; Behind the 90h, air flow is controlled at 20m 3/ h, (the mark condition is equivalent to empty tower gas velocity 9.5cm/s), ventilation is than being 1.98vvm.Supplementary carbon source is a glucose, and sugared concentration is at 82% (w/v), and stream dosage 0~60h is at 1L/h; 60~100h, the stream dosage is at 1.5L/h; Behind the 100h, the stream dosage is at 1.8L/h; The sulphur ammonium concentration is at 35% (w/v), and 0~60h flows dosage at 0.11L/h; 60~100h, the stream dosage is at 0.14L/h; Behind the 100h, the stream dosage is at 0.17L/h; Toluylic acid concentration is at 38% (w/v), and at 0~60h, the stream dosage is at 0.10L/h; 60~100h, the stream dosage is at 0.14L/h; Behind the 100h, the stream dosage is at 0.19L/h; The highest mycelial concentration 40% in the fermenting process, dissolved oxygen concentration maintains more than 35%.During fermentation ends, obtaining penicillin fermentation unit is 100943u/ml.

Claims (5)

1. Airlift circulating reactor that is used for penicillin fermentation, it comprise tower body, with the coaxial mounted guide shell of tower body, air-distributor, wherein guide shell is a single hop or multistage; It is characterized in that; The tower body bottom of said Airlift circulating reactor is a conversion zone, the gas-liquid separation section of top for enlarging, and the aspect ratio of gas-liquid separation section and conversion zone is 0.15~0.25; The diameter ratio is 1.25~1.42; The tower body height overall is 4.5~8 with the ratio of conversion zone internal diameter, and guide shell internal diameter and conversion zone internal diameter ratio are 0.5~0.78, and guide shell height and conversion zone aspect ratio are 0.9~0.65.
2. a kind of Airlift circulating reactor that is used for penicillin fermentation according to claim 1; It is characterized in that the bottom of going up of said guide shell is the jagged edges that is made up of vee, the degree of depth 10~20mm of each breach; Width 10~20mm, distance 5~15mm between breach.
3. Airlift circulating reactor according to claim 1 and 2, wherein air-distributor guarantees that air edge and axial angle are 30 °~60 ° conical surface ejection, and egress line speed is not less than 2m/s.
4. an Airlift circulating reactor that utilizes claim 1-3 carries out the method for penicillin fermentation; It is characterized in that; After Penicllium chrysogenum bacterial strain seed culture is accomplished, begin fermentation in the inoculum size access Airlift circulating reactor according to 8~10% (v/v), leavening temperature is 20~30 ℃; PH is 6.0~7.0; The ventilation of fermentation whole process is than being controlled at 0.8~3vvm, and through regulating the ventilation ratio, the control dissolved oxygen is more than 30%; Fermentation pressure is 0.08~0.1Mpa; Fermentation period is 160~170h; Whole fermentation process control fermented liquid mycelial concentration is 35~45%.
5. the method for penicillin fermentation according to claim 4 is characterized in that, fermenting process need be added carbon source, nitrogenous source and precursor, and it is glucose that stream adds carbon source, and glucose concn is controlled at 70~85% (w/v), and glucose stream dosage is 1~2L/h; It is ammonium sulfate that stream adds nitrogenous source, and the concentration of ammonium sulfate is controlled at 30~40% (w/v), and the ammonium sulfate stream dosage is 0.1~0.2L/h; It is toluylic acid that stream adds precursor, and toluylic acid concentration is controlled at 30~40% (w/v), and toluylic acid stream dosage is 0.1~0.2L/h.
CN2012102015619A 2012-06-07 2012-06-07 Airlift type loop reactor and method for penicillin fermentation by using the same Pending CN102732416A (en)

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WO2015091455A1 (en) * 2013-12-17 2015-06-25 Dpx Holdings B.V. Bioreactor
WO2017068265A1 (en) * 2015-10-23 2017-04-27 Gg Coriolis Liquid-medium digester with gas-flow-based agitation, comprising an automatic device for establishing a fluid communication between the upflow and downflow spaces according to the height of the medium
CN106916727A (en) * 2017-03-31 2017-07-04 江南大学 Assemble the airlift reactor of baffling sieve plate
EP3766982A1 (en) * 2019-07-18 2021-01-20 Delft Advanced Biofuels B.V. Integrated system for biocatalytically producing and recovering an organic substance
CN117757595A (en) * 2023-12-20 2024-03-26 中国科学院天津工业生物技术研究所 Gas-lift type bioreactor for strengthening liquid flow circulation

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Cited By (12)

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Publication number Priority date Publication date Assignee Title
WO2015091455A1 (en) * 2013-12-17 2015-06-25 Dpx Holdings B.V. Bioreactor
WO2017068265A1 (en) * 2015-10-23 2017-04-27 Gg Coriolis Liquid-medium digester with gas-flow-based agitation, comprising an automatic device for establishing a fluid communication between the upflow and downflow spaces according to the height of the medium
FR3042795A1 (en) * 2015-10-23 2017-04-28 Gg Coriolis CLOSER FOR LIQUID ENVIRONMENT WITH AUTOMATIC FLUID COMMUNICATION BETWEEN ASCENDING AND DESCENDING CIRCULATIONS IN RELATION TO THE LEVEL OF THE LIQUID ENVIRONMENT
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CN108138107B (en) * 2015-10-23 2021-11-26 拜奥拉公司 Fermentation device for liquid culture medium
CN106916727A (en) * 2017-03-31 2017-07-04 江南大学 Assemble the airlift reactor of baffling sieve plate
EP3766982A1 (en) * 2019-07-18 2021-01-20 Delft Advanced Biofuels B.V. Integrated system for biocatalytically producing and recovering an organic substance
WO2021010822A1 (en) * 2019-07-18 2021-01-21 Delft Advanced Biofuels B.V. Integrated system for biocatalytically producing and recovering an organic substance
CN114502738A (en) * 2019-07-18 2022-05-13 代尔夫特先进生物燃料有限公司 Integrated system for biocatalytic production and recovery of organic matter
AU2020315676B2 (en) * 2019-07-18 2023-09-21 Delft Advanced Biofuels B.V. Integrated system for biocatalytically producing and recovering an organic substance
CN117757595A (en) * 2023-12-20 2024-03-26 中国科学院天津工业生物技术研究所 Gas-lift type bioreactor for strengthening liquid flow circulation

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Application publication date: 20121017