JP2012115783A - Method for washing separation membrane module for continuous fermentation and device for separating membrane for continuous fermentation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for washing a separation membrane module for stably maintaining high productivity over an extended time period by a simple operation method in a method for manufacturing a chemical product by a continuous fermentation method.SOLUTION: In the method for washing the separation membrane module in continuous fermentation, a fermentation raw materials is continuously introduced to a fermentation tank, a culture solution containing a microorganism and a chemical product is filtrated by using the separation membrane module, and a permeated liquid containing the chemical product is taken out continuously while non-permeated liquid is kept in the fermentation tank. After back pressure washing using water including an oxidizing agent is carried out, water including a reducing agent is filtrated.

Description

  The present invention continuously introduces fermentation raw materials into a fermenter, filters a culture solution containing microorganisms and chemicals using a separation membrane module, and continuously holds the non-permeate in the fermenter The present invention relates to a method for washing a separation membrane module and continuous membrane separation apparatus for continuous fermentation in which continuous permeate is taken out.

  Fermentation, which is a material production method involving the cultivation of microorganisms and cultured cells, is largely divided into (1) batch fermentation (Batch fermentation) and fed-batch fermentation (Fed-Batch or Semi-Batch fermentation), and (2) continuous. It can be classified as a fermentation method (Continuous fermentation method). The batch and fed-batch fermentation methods are simple in terms of equipment, and the culture is completed in a short time. In the case of product fermentation by pure bacterial culture, contamination by other bacteria other than the culture required for the culture may occur. There is a merit that is low. However, with the passage of time, the concentration of the product in the culture solution becomes higher, and the productivity and the yield are reduced due to the influence of product inhibition and increase in osmotic pressure. For this reason, it is difficult to stably maintain a high yield and high productivity over a long period of time.

  The continuous fermentation method can maintain a high yield and high productivity over a long period of time compared to the batch and fed-batch fermentation methods described above by avoiding accumulation of the target substance in the fermenter. Conventional continuous culture is a culture method in which a fresh medium is supplied to a fermentor at a constant rate, and the same amount of culture medium is discharged out of the tank to keep the amount of liquid in the fermenter constant. In batch culture, culture is terminated when the initial substrate concentration is consumed, but in continuous culture, culture can theoretically be continued indefinitely. That is, in theory, it can be fermented indefinitely.

  However, in the conventional continuous culture, the microorganisms are discharged out of the tank together with the culture solution, and it is difficult to maintain a high microorganism concentration in the fermenter. Therefore, when performing fermentation production, fermentation production efficiency per fermentation volume can be improved if the microorganisms to be fermented can be kept at a high concentration. For this purpose, it is necessary to hold or reflux the microorganisms in the fermenter.

  As a method for retaining or refluxing microorganisms in the fermenter, the discharged culture solution is subjected to solid-liquid separation by centrifugation, and the microorganisms as precipitates are returned to the fermentor, or the solid content is obtained by filtration. A method of separating microorganisms and discharging only the culture supernatant to the outside of the tank can be mentioned. However, the method by centrifugation is not practical because of high power cost. Since the filtration method requires high pressure for filtration as described above, most studies have been conducted at the laboratory level. As an example, “Applied Microbiol. Biotechnol.”, 32, 269-273 (1989). (Toshihiko Hirao et.al.) includes L- Continuous culture methods have been disclosed for the fermentation of glutamic acid and L-lysine. However, in these examples, although continuous fermentation is performed, in order to continuously supply raw materials to the culture solution and to extract the culture solution containing microorganisms and cultured cells, the microorganisms and cultured cells in the culture solution are extracted. Is extracted and diluted, and the concentration of microorganisms in the fermenter decreases, so the improvement in production efficiency has been limited.

  Therefore, in the continuous fermentation method, microorganisms and cultured cells are separated and filtered with a separation membrane, and the product is recovered from the filtrate, and at the same time, the separated microorganisms and cultured cells are held or refluxed in the culture solution, A method of maintaining a high microorganism or cell concentration has been proposed. For example, Japanese Patent Application Laid-Open No. 5-95778, Japanese Patent Application Laid-Open No. Sho 62-138184, and Japanese Patent Application Laid-Open No. Hei 10-174594 disclose technologies related to continuous membrane separation in a continuous fermentation apparatus using a ceramic membrane. . These technologies have shown the superiority of continuous membrane separation fermentation that maintains higher microorganism and cultured cell concentrations by membrane separation than existing continuous fermentation. However, the disclosed technology has problems such as a decrease in filtration flow rate and filtration efficiency due to clogging of the ceramic film, and back pressure cleaning or the like is performed to prevent clogging.

  Recently, techniques for continuous culture using a continuous culture apparatus using an organic polymer separation membrane have been proposed (see, for example, International Publication No. 07/097260 and Japanese Patent Application Laid-Open No. 2008-212138). In this proposal, a continuous culture apparatus having a tank for culturing microorganisms or cultured cells and a tank for performing membrane separation of the desired fermentation product, microorganisms and cultured cells from the culture solution is used. As a result, various chemical products can be produced at a higher production rate than the batch culture method and the fed-batch culture method.

  Furthermore, Japanese Patent Application Laid-Open No. 2010-22321 discloses a method for producing a chemical product by a continuous culture method that stably maintains high productivity over a long period of time. However, it is necessary to control the recovery rate of the filtrate volume per circulating fluid volume, which increases costs such as installing a flow meter in the circulation line. It is desired.

  In such continuous fermentation technology using a separation membrane, improvement in water permeability performance is required from the viewpoint of cost reduction, and the facility cost is reduced by reducing the membrane area and downsizing the apparatus with a separation membrane having excellent water permeability performance.・ Attempts to reduce membrane replacement costs and installation area. From such a viewpoint of cost, a hollow fiber membrane having a large filtration area with respect to volume has attracted attention.

  However, such separation membranes, including hollow fiber membranes, are subject to SS (Suspended Solid) and adsorbate adhering to the filtration surface through the filtration operation, resulting in a decrease in filtration capacity and the inability to obtain the required amount of filtrate. There is. As a method for suppressing clogging of microorganisms and cultured cells, several techniques relating to cleaning of porous separation membranes and setting of filtration conditions have been proposed, but none of them is sufficient. For example, as a method for cleaning the porous separation membrane, a method of backwashing the porous separation membrane with warm water (Patent Document 1), a method of backwashing the porous separation membrane with filtered permeated water (Patent Document 2), etc. Are both porous separation membrane cleaning methods when the fermentation product is filtered and recovered from the culture broth after completion of fermentation, and the microorganism or cultured cells are continuously retained or refluxed in the culture broth after the filtration treatment. When applied to a fermentation method, it is difficult to maintain high productivity of fermentation because dirt on the membrane surface due to organic matter cannot be effectively washed.

  On the other hand, in the field of water treatment using separation membranes, air is introduced to the raw water side of the membrane, the membranes are shaken, and the membranes are brought into contact with each other to remove air adhering substances on the membrane surface or membrane filtration. Physical cleaning such as back pressure cleaning that pushes the membrane filtrate with pressure in the opposite direction to eliminate contaminants adhering to the membrane surface and pores has been put into practical use, further enhancing the cleaning effect Therefore, as disclosed in Patent Document 3, sodium hypochlorite is added to the backwash water, or ozone-containing water is used as the backwash water as in Patent Document 4. The oxidizing agent has the effect of decomposing and removing organic substances such as fermentation by-products and microorganism-derived proteins adhering to the membrane surface and membrane pores.

  However, in recent years, a method for concentrating and purifying a fermentation filtrate containing a chemical product produced by continuous fermentation using a reverse osmosis membrane or a nanofiltration membrane (hereinafter collectively referred to as a semipermeable membrane) is disclosed in JP 2009 -34030 and the like. Therefore, if the oxidant remains in the separation membrane module or in the secondary pipe on the filtration side after oxidative decomposition of the organic matter attached to the membrane surface with the oxidant as in the above method, Membrane filtrates often contain high concentrations of oxidants. When applying semi-permeable membrane treatment for concentration and purification of fermentation filtrates, separation membrane modules are especially prone to causing oxidative degradation of semi-permeable membranes, especially semi-permeable membranes made of polyamide. It is necessary to thoroughly wash the inside of the pipe or the secondary pipe on the filtration side with raw water or a membrane filtrate, or to add a reducing agent such as sodium thiosulfate or sodium bisulfite to reduce and neutralize the oxidizing agent. Furthermore, when a high concentration oxidizing agent remains in the separation membrane module, adverse effects such as degradation of microorganisms by the oxidizing agent can be considered.

  When performing the above neutralization, the remaining oxidizing agent is being efficiently reduced simply by washing the separation membrane module or the secondary pipe on the filtration side with a fermentation medium, fermentation neutralizer, membrane filtrate, etc. Since it cannot be summed, it is necessary to always add a reducing agent before the semipermeable membrane module, and the chemical cost is increased. In addition, in the water treatment field, in a fresh water generation method of filtering raw water while adding an oxidizing agent, in Patent Document 5, a method of periodically cleaning the primary side of a separation membrane module with a bisulfite solution as a reducing agent, Patent Document 6 proposes a method of regularly performing back-pressure washing with washing water containing a reducing agent. However, since the membrane filtrate between the washings with the reducing agent contains an oxidizing agent, it is necessary to always add the reducing agent before the semipermeable membrane module, which increases the chemical cost. There was a problem.

  As described above, in the conventional technique, an appropriate cleaning method for continuous fermentation operation of microorganisms using membrane separation technology has not been studied, and while maintaining membrane filterability by performing membrane surface cleaning, and by fermentation There is a need to develop methods to increase the productivity of chemicals.

JP 2000-317273 A JP 11-215980 A JP 2001-79366 A JP 2001-187324 A JP 2006-305444 A JP 2008-29906 A

  An object of the present invention is to provide a method for washing a separation membrane module for maintaining a high productivity stably for a long time by a simple operation method in a chemical production method by a continuous fermentation method.

  In order to solve the above problems, the present invention has the following configuration.

  (1) The fermentation raw material is continuously introduced into the fermenter, the culture solution containing microorganisms and chemicals is filtered using a separation membrane module, and the chemicals are contained while continuously retaining the non-permeate in the fermenter. This is a method for washing a separation membrane module in continuous fermentation for removing permeate, and after performing reverse pressure washing for supplying water containing an oxidizing agent from the secondary side to the primary side of the separation membrane module, A method for washing a separation membrane module for continuous fermentation, comprising filtering water containing a reducing agent.

  (2) The continuous fermentation according to (1), wherein at least a part of the water membrane filtrate containing the reducing agent is discharged out of the system from a bypass line provided on the secondary side of the separation membrane module. Cleaning method for separation membrane module.

  (3) Before or after filtering the water containing the reducing agent, from the secondary side to the primary side of the separation membrane module, a liquid containing at least part of the fermentation raw material and at least part of the neutralizing agent used for fermentation are included. The method for washing a separation membrane module for continuous fermentation according to any one of (1) and (2), wherein a liquid containing at least one selected from the group consisting of a liquid and a membrane filtrate is supplied.

  (4) It is characterized by holding water containing an oxidant in the separation membrane module for a predetermined time after performing reverse pressure cleaning for supplying water containing an oxidant from the secondary side to the primary side of the separation membrane module. The method for washing a separation membrane module for continuous fermentation according to any one of (1) to (3).

  (5) The water containing the oxidant is retained before, during, or after the reverse pressure cleaning for supplying the water containing the oxidant from the secondary side to the primary side of the separation membrane module or in the separation membrane module. The method for cleaning a separation membrane module for continuous fermentation according to any one of (1) to (4), wherein gas cleaning is performed for at least a part of the running time.

  (6) The method for washing a separation membrane module for continuous fermentation according to any one of (1) to (5), wherein at least part of the permeate containing a chemical is filtered through a semipermeable membrane.

  (7) Fermenter into which fermentation raw materials are continuously introduced, a separation membrane module that separates a culture solution containing microorganisms and chemicals into permeate and non-permeate containing chemicals, and a separation membrane from the fermenter A culture solution supply means for supplying a culture solution to the module, a non-permeate supply means for supplying a non-permeate to the fermenter from the separation membrane module, and water containing an oxidizing agent from the secondary side to the primary side of the separation membrane module A continuous fermentation membrane separation device comprising: an oxidizing agent supply means for supplying the water; and a reducing agent supply means for supplying water containing a reducing agent to the primary side of the separation membrane module.

  (8) The membrane separator for continuous fermentation according to (7), comprising a bypass line that communicates the secondary side of the separation membrane module with the outside of the system.

  (9) The continuous separation membrane separator according to any one of (7) and (8), wherein gas is supplied to a pipe from the fermenter to the separation membrane module and / or to a lower portion of the separation membrane module.

  (10) The membrane separator for continuous fermentation according to any one of (7) to (9), comprising a semipermeable membrane module for filtering at least a part of the membrane filtrate.

  According to the present invention, the filterability of the separation membrane can be stabilized over a long period of time, and further, the fermentation performance can be enhanced. In the fermentation industry, chemical products that are fermentation products can be stably produced at low cost. It becomes possible to produce.

It is the schematic of an example of the membrane separator for continuous fermentation used by this invention. It is a figure which shows the time-dependent change of the microbial cell density | concentration which concerns on an Example and a comparative example. It is a figure which shows the time-dependent change of the D-lactic acid production rate concerning an Example and a comparative example. It is a figure which shows the time-dependent change of the transmembrane pressure difference which concerns on an Example and a comparative example.

  The fermenter used in the present invention is made of a material excellent in pressure resistance, heat resistance, and dirt resistance, and is made of a solid material, a liquid, or a gas necessary for fermentation, such as a cylindrical shape or a polygonal shape, such as a fermentation raw material, a microorganism, Any shape can be used as long as it can be injected and stirred, sterilized as necessary, and sealed. Considering the fermentation raw materials, the culture solution, and the stirring efficiency of microorganisms, the cylindrical type is preferable. The fermenter used in the present invention is provided with a pressure gauge in the fermenter in order to prevent germs from entering and growing inside the fermenter from the outside of the fermenter, and always maintains the pressure in the fermenter in a pressurized state. It is preferable.

  The fermentation raw material for microorganisms and cultured cells used in the present invention may be any material that promotes the growth of microorganisms and cultured cells for fermentation and can produce a desired chemical product that is a desired fermentation product. As a fermentation raw material, for example, a normal liquid medium that appropriately contains a carbon source, a nitrogen source, inorganic salts, and if necessary, organic micronutrients such as amino acids and vitamins is preferably used. If it is a liquid that partially promotes the growth of microorganisms and cultured cells to be fermented and can produce a chemical product that is a desired fermentation product, for example, waste water or sewage can be used as it is or sterilized. Or may be used after adding fermentation raw materials.

  Examples of the carbon source include sugars such as glucose, sucrose, fructose, galactose and lactose, starch containing these sugars, starch hydrolysates, sugar cane molasses, sugar beet molasses, cane juice, sugar beet molasses or cane juice. Extracts or concentrates, sugar beet molasses or cane juice filtrate, syrup (high test molasses), sugar beet molasses or cane juice purified or crystallized raw sugar, vegetable molasses or cane juice purified or crystallized Purified saccharides, organic acids such as acetic acid and fumaric acid, alcohols such as ethanol, glycerin and the like are used. Sugars are the first oxidation products of polyhydric alcohols, and are carbohydrates that have one aldehyde group or ketone group, sugars with aldehyde groups are classified as aldoses, and sugars with ketone groups are classified as ketoses. Point to.

  Examples of the nitrogen source include ammonia gas, aqueous ammonia, ammonium salts, urea, nitrates, and other auxiliary organic nitrogen sources such as oil cakes, soybean hydrolysates, casein decomposition products, Other amino acids, vitamins, corn steep liquor, yeast or yeast extract, meat extract, peptides such as peptone, various fermented cells and hydrolysates thereof are used.

  Moreover, as said inorganic salt, a phosphate, magnesium salt, calcium salt, iron salt, manganese salt etc. can be used suitably, for example.

  What is necessary is just to add a nutrient required for microbial cell growth to a fermentation raw material so that microbial cell growth may be performed continuously. Maintaining a high concentration of microorganisms or cultured cells in the culture solution as long as the environment of the culture solution is not appropriate for the growth of microorganisms or cultured cells does not increase the rate of death, it is efficient productivity It is preferable to obtain

  As the microorganisms and cultured cells used in the present invention, eukaryotic cells or prokaryotic cells are used, for example, yeasts such as baker's yeast often used in the fermentation industry, bacteria such as E. coli, lactic acid bacteria, coryneform bacteria, filamentous forms, etc. Examples include fungi, actinomycetes, animal cells and insect cells. The microorganisms and cells used may be those isolated from the natural environment, or may be those whose properties have been partially modified by mutation or genetic recombination.

  The most distinguishing feature of eukaryotic cells used in the present invention is clearly distinguished from prokaryotes having a structure called a cell nucleus (nucleus) in the cell and not having a cell nucleus (nucleus). In the present invention, yeast is more preferably used among the eukaryotic cells. Suitable yeasts in the present invention include, for example, yeasts belonging to the genus Saccharomyces and yeasts belonging to Saccharomyces cerevisiae.

  The most prominent feature of the prokaryotic cell used in the present invention is that it does not have a structure called a cell nucleus (nucleus) in the cell, and is clearly distinguished from a eukaryote having a cell nucleus (nucleus). In the present invention, lactic acid bacteria can be preferably used among the eukaryotic cells.

  The continuous culturing operation performed while growing fresh microbial cells capable of fermentation production is usually preferably performed in a single fermenter in terms of culture management. However, the number of fermenters does not matter as long as it is a continuous fermentation culture method that produces a product while growing cells. A plurality of fermenters may be used because the capacity of the fermenter is small. In that case, high productivity of the fermentation product can be obtained even when continuous fermentation is performed by connecting a plurality of fermenters in parallel or in series by piping.

  In the present invention, fermentation culture of microorganisms can usually be performed at a pH of 3 to 10 and a temperature of 15 ° C. to 65 ° C. The pH of the fermentation broth is adjusted to a predetermined value within the above range with an inorganic acid or an organic acid, an alkaline substance, urea, calcium hydroxide, calcium carbonate, ammonia gas, and the like.

  In the method for producing a chemical product according to the present invention, batch culture or fed-batch culture may be performed at the initial stage of culture to increase the microorganism concentration, and then continuous culture (drawing) may be started. In the method for producing a chemical product of the present invention, after increasing the microorganism concentration, a high concentration of bacterial cells may be seeded, and continuous culture may be performed at the start of culture. In the method for producing a chemical product according to the present invention, it is possible to supply a raw material culture solution and extract a culture from an appropriate time. The starting times of the supply of the raw material culture solution and the withdrawal of the culture are not necessarily the same. Further, the supply of the raw material culture solution and the withdrawal of the culture may be continuous or intermittent.

  The separation membrane used in the separation membrane module of the present invention is not limited to organic membranes and inorganic membranes, but is cultured like polyvinylidene fluoride, polysulfone, polyethersulfone, polytetrafluoroethylene, polyethylene, polypropylene, and ceramic membranes. Any separation membrane can be used as long as it can be used for liquid filtration and has durability against gas cleaning. Among these, a separation membrane made of polyvinylidene fluoride, which is less likely to be contaminated by the culture solution, is easy to clean, and has excellent durability against cleaning with gas, is preferable.

  The separation membrane used in the present invention is preferably a porous membrane having pores having an average pore diameter of 0.001 μm or more and less than 10 μm in order to effectively separate microorganisms in the culture solution. In addition, the shape of the separation membrane may be any shape such as a flat membrane and a hollow fiber membrane, but a hollow fiber membrane having a membrane area wider than the module volume is preferable. The average pore diameter of the membrane can be determined according to the method described in ASTM: F316-86 (also known as the half dry method). Note that what is determined by this half dry method is the average pore size of the minimum pore size layer of the membrane.

  In the present invention, measurement of the average pore size by the half-dry method was performed using ethanol as the liquid used and measuring at 25 ° C. and a pressure increase rate of 0.001 MPa / second as standard measurement conditions. The average pore diameter [μm] is obtained from the following formula.

Average pore diameter [μm] = (2860 × surface tension [mN / m]) / half dry air pressure [Pa]
Since the surface tension of ethanol at 25 ° C. is 21.97 mN / m (The Chemical Society of Japan, Chemical Handbook Basic Edition, Rev. 3, II-82, Maruzen Co., Ltd., 1984), standard measurement conditions in the present invention In the case of, it can be obtained by the following formula.

Average pore diameter [μm] = 62834.2 / (half dry air pressure [Pa])
The shape of the separation membrane is not particularly limited, and may be a hollow fiber membrane, a flat membrane, a tubular membrane, a monolith membrane, or the like. In the case of a pressure-type separation membrane module, an external pressure type or an internal pressure type may be used, but an external pressure type is preferable from the viewpoint of simplicity of pretreatment.

  As a filtration flow rate control method for membrane filtration, there is no problem whether it is constant flow filtration or constant pressure filtration, but constant flow filtration is preferred from the viewpoint of easy control of the production water volume of the filtrate. .

  In the case of an external pressure type hollow fiber membrane, the diameter of the hollow fiber membrane is preferably 0.5 mm or more and 3 mm or less. If the outer diameter is smaller than this range, the resistance of the filtrate flowing in the hollow fiber membrane is strong. If it is large, the hollow fiber membrane may be crushed by the external pressure due to the culture solution or gas. In the case of the internal pressure type hollow fiber membrane, the inner diameter is preferably 0.5 mm or more and 3 mm or less. When the inner diameter is smaller than this range, the resistance of the culture fluid flowing in the hollow fiber membrane is strong, and when the inner diameter is larger, the membrane surface area becomes narrow and the number of modules used may increase.

  The case of the separation membrane module in the present invention is made of a material having excellent pressure resistance, and may be any shape that can supply a culture solution to the primary side of the module, such as a cylindrical shape or a polygonal tube shape. Considering the flow of liquid and handling properties, a cylindrical type is preferable.

  The membrane filtration method in the present invention may be total filtration or cross flow filtration. However, in the case of microorganisms in continuous fermentation operation, membrane dirt substances such as microorganisms and membrane clogging substances often adhere to the membrane, so scrubbing filtration is performed while removing the membrane dirt substances by the shear force of the culture fluid flow by cross-flow filtration. Preferably it is done.

  In the present invention, the gas supplied for continuous fermentation is preferably a gas containing oxygen in the case of aerobic fermentation. Further, pure oxygen may be supplied, or a gas that does not adversely affect fermentation, for example, a gas in which the concentration of oxygen is adjusted by mixing air, nitrogen, carbon dioxide, methane gas, or the like may be used. If it is necessary to increase the oxygen supply rate in the culture, oxygen is added to the air to keep the oxygen concentration preferably at 21% or higher, the fermentation broth is pressurized, the stirring speed is increased, or the aeration rate is increased. The following means can be used. On the other hand, in the case of anaerobic fermentation, if it is necessary to lower the supply rate of oxygen, it is also possible to supply a gas containing no oxygen, such as carbon dioxide, nitrogen and argon, mixed with air.

  As a driving force for filtration, a transmembrane differential pressure can be generated in the separation membrane by a siphon using a liquid level difference (water head difference) of the fermentation culture solution and the porous membrane treated water, or a cross flow circulation pump. Moreover, you may install a suction pump in the secondary side of a separation membrane module as a driving force of filtration. Further, when a cross flow circulation pump is used, the transmembrane pressure difference can be controlled by the suction pressure. Furthermore, the transmembrane pressure difference can be controlled by the pressure of the gas or liquid that introduces the pressure on the fermentation broth side. When these pressure controls are performed, the pressure difference between the pressure on the fermentation broth side and the pressure on the porous membrane treated water side can be used as the transmembrane pressure difference, which can be used to control the transmembrane pressure difference. Further, a transmembrane differential pressure can be controlled by installing a valve on the secondary side of the separation membrane module and controlling the valve. In addition, the transmembrane pressure difference can be controlled more effectively by using at least one of the above methods.

  In the present invention, the reverse pressure cleaning is performed when the separation membrane module is stopped by filtration or scrubbed cleaning is performed on the secondary side of the separation membrane module using a tank made of a material capable of containing a cleaning liquid, a cleaning pipe, and a pump. The cleaning liquid is put into the primary side of the separation membrane module from the secondary side of the separation membrane module. In addition, as a driving force, the cleaning liquid can be injected into the separation membrane module by a siphon that utilizes the liquid level difference (water head difference) between the cleaning liquid and the fermentation broth. The piping for back pressure cleaning in the present invention has durability against the cleaning liquid, and the piping includes a pressure gauge, a flow meter, a valve, a sterilization device, a sterilization filter, and the like as necessary. Can be installed. At the time of back pressure washing in the present invention, a valve is provided in the filtrate pipe and a valve is provided in the washing pipe so that the washing liquid does not flow toward the filtrate tank, and these valves are controlled. It is desirable to provide a control device and automatically control the supply with a timer or the like. Here, the reverse pressure cleaning is a method of removing the fouling substance on the membrane surface by sending a cleaning liquid from the porous membrane treated water side to the fermentation culture solution side.

  As the oxidizing agent in the present invention, an aqueous sodium hypochlorite solution, an aqueous hydrogen peroxide solution, an aqueous chloramine solution, and the like can be used, but an aqueous sodium hypochlorite solution is preferred from the viewpoint of ease of use and cost. The hypochlorite aqueous solution may contain a basic compound such as sodium hydroxide or calcium hydroxide as long as the effects of the invention are not impaired.

  As the concentration of the oxidizing agent, the concentration of the hypochlorite aqueous solution is such that the free chlorine concentration is in the range of 10 ppm to 5,000 ppm, more preferably 100 ppm to 3,000 ppm. If the free chlorine concentration is higher than this range, the cost of treating wastewater is high, and if it is lower than this range, the cleaning effect may not be sufficiently obtained. Moreover, the injection | pouring rate of an oxidizing agent is the range of 0.5 times or more and 5 times or less of the membrane filtration rate, More preferably, they are 1 time or more and 3 times or less. When the back pressure washing rate is higher than this range, the filtration membrane module may be damaged, and when it is lower than this range, the washing effect and the microorganism control effect may not be sufficiently obtained.

  The counter pressure cleaning cycle using the oxidizing agent can be determined by the differential pressure and the change in the differential pressure. The counter pressure washing cycle is in the range of 0.1 times / hour to 12 times / hour, more preferably 4 times / hour to 8 times / hour. If the counter pressure cleaning cycle is larger than this range, the filtration membrane may be damaged, and if it is smaller than this range, the cleaning effect and the microorganism control effect may not be sufficiently obtained.

  The back pressure cleaning time with the oxidizing agent can be determined by the back pressure cleaning cycle, the membrane differential pressure, and changes in the membrane differential pressure. The back pressure washing time is in the range of 5 seconds / times to 300 seconds / times, more preferably 30 seconds / times to 120 seconds / times. If the back pressure cleaning time is longer than this range, the filtration membrane may be damaged, and if it is shorter than this range, the cleaning effect may not be sufficiently obtained.

  As the oxidant storage tank, the cleaning agent supply pump, the piping and valves from the cleaning agent storage tank to the module, those having excellent chemical resistance may be used. The cleaning agent can be injected manually, but a filtration / backwash control device is provided, and the filtration pump and filtration side valve, cleaning agent supply pump and cleaning agent supply valve can be automatically controlled by a timer, etc. desirable.

  As the reducing agent in the present invention, inorganic reducing agents such as sodium bisulfite, sodium sulfite, sodium thiosulfate and the like can be used. The concentration of the reducing agent may be in the range of 1 ppm or more and 5000 ppm or less, and is 1 to 5 times the theoretical concentration necessary for reducing and neutralizing the oxidant remaining in the separation membrane module or the secondary pipe on the filtration side. It is more preferable to make it below.

  The period for filtering the water containing the reducing agent is determined in combination with the counter pressure washing period using the oxidizing agent. If necessary, the reducing agent can be washed after back-pressure washing with a plurality of oxidizing agents as required, such as the effect on microorganisms.

  The time for filtering the water containing the reducing agent and the injection rate are preferably carried out until the oxidizing agent in the separation membrane module or in the secondary pipe on the filtration side is reduced and neutralized. When sodium chlorate is used, it is preferable to carry out until the free chlorine concentration in the secondary pipe on the filtration side is about 0.1 ppm. As a method for measuring the free chlorine concentration, a DPD method, a current method, an absorptiometric method, or the like is used. For the measurement, water is collected as appropriate, and the free chlorine concentration is measured by the DPD method and the current method, or the free chlorine concentration is measured by a continuous automatic measuring instrument using the absorptiometry. By these measurements, it is preferable to monitor the free chlorine concentration and determine and adjust the time for filtering the water to which the reducing agent has been added.

  As the piping and valves from the reducing agent storage tank, the reducing agent supply pump, and the reducing agent storage tank to the reducing agent inlet, those having excellent chemical resistance may be used. Although it is possible to inject the reducing agent manually, it is desirable to provide a control device and inject by automatically controlling the valve and the supply pump with a timer or the like.

  Next, the continuous fermentation apparatus used by this invention is demonstrated using figures.

  FIG. 1 is a schematic diagram for illustrating and explaining a continuous fermentation apparatus in which the method for supplying an oxidizing agent and a reducing agent of the present invention is used. In FIG. 1, the continuous fermentation apparatus basically includes a fermentation tank 1, a separation membrane module 2, a filtrate storage tank 23, an oxidant tank 24, and a reducing agent tank 20.

  In FIG. 1, in the fermenter 1, the medium supply pump 9 is controlled by the level sensor / control device 6, the medium is introduced into the fermenter 1, and the fermentation culture in the fermenter 1 is performed by the stirring device 4 as necessary. The liquid is agitated, and the temperature of the culture solution is controlled by the temperature control device 3 as necessary, and the necessary gas can be supplied by the fermenter gas supply device 21 as necessary. When the gas is supplied, the supplied gas can be recovered and recycled and supplied again by the fermenter gas supply device 21. In addition, if necessary, the neutralizing agent supply pump 10 is controlled by the pH sensor / control device 5 to adjust the pH of the fermentation broth, whereby highly productive fermentation production can be performed.

  Further, the culture solution in the apparatus is supplied from the fermenter 1 to the separation membrane module 2 by the circulation pump 8 by opening the circulation control valve 18. When supplying the culture solution to the module, the reducing agent supply control valve 19 can be closed as necessary. If necessary, the culture medium and gas can be supplied to the module simultaneously or intermittently using the module gas supply control valve 17 and the module gas supply device 22.

  The culture solution containing chemicals is filtered and separated into a filtrate containing microorganisms and chemicals by the separation membrane module 2, and can be taken out from the apparatus system. Here, a large number of hollow fiber membranes are incorporated in the separation membrane module 2, but in some cases, a module can be produced with a flat membrane and used. Moreover, the microorganisms filtered and separated remain in the apparatus system, so that the microorganism concentration in the apparatus system can be kept high, and fermentation production with a high production rate is possible. Here, the filtration step by the separation membrane module 2 can be carried out by using pressure from the circulation pump 8 without using any special power. However, if necessary, a filtration pump 11 is provided to reduce the amount of the culture solution. It can be adjusted appropriately. In the filtration step, it is desirable that the backwash valve 13 is closed so that the filtrate does not enter the oxidant tank 24.

  Here, the obtained filtrate is sent to the filtrate reservoir 23, but if necessary, a semipermeable membrane module (not shown) is separately provided as a subsequent process to remove solute contained in the filtrate. The chemical obtained by fermentation and filtration can also be concentrated by separating the membrane filtrate into concentrated water in which the solute contained in the filtrate is concentrated.

  In the present invention, as a backwashing process, a backwashing pipe is provided on the secondary side of the separation membrane module 2, and an oxidant is introduced using the backwash pump 12 and the backwash valve 13. At this time, as necessary, the filtration pump 11, the filtration valve 14, the discharge control valve 15, the circulation pump 8, the circulation valve 18, the circulation return control valve 16, the reducing agent supply pump 7, the reducing agent supply control valve 19, and the module gas. At least one or more of the supply control valve 17 and the module gas supply device 22 can be stopped or closed. In order to prevent the oxidizing agent from entering the reducing agent tank 20, it is preferable to close the reducing agent supply control valve 19, and in order to prevent the oxidizing agent from affecting the filtrate, it is preferable to close the filtration valve 14. Further, it is preferable to close the discharge control valve 15 in order to prevent the oxidant from being discharged due to the pressure to put the oxidant into the separation membrane module 2, and the oxidant is effectively used for cleaning the separation membrane module 2. In order to prevent a large amount of unreacted oxidant from entering the fermenter 1, it is desirable to stop the circulation pump 8 and close the circulation control valve 18 and the circulation return control valve 16. However, the operation of the pump and the valve are controlled by the positional relationship and pressure relationship of each tank, the influence of the oxidizing agent on the culture solution, microorganisms and filtrate, the concentration of the oxidizing agent, the concentration of the unreacted oxidizing agent, Judgment is made based on the oxidant concentration and the influence of the concentration on the semipermeable membrane module, and can be controlled as necessary.

  There is a concern that the high-concentration oxidant remaining in the separation membrane module 2 or the secondary pipe after the backwashing of the separation membrane module 2 with the oxidant may adversely affect microorganisms in the culture solution, There is a concern that the high concentration oxidant flows into the filtrate storage tank 23 and causes oxidation of the filtrate, and further, the high concentration oxidant flows into the subsequent semipermeable membrane module and the semipermeable membrane is oxidized and deteriorated. In the present invention, after performing the back pressure cleaning of the separation membrane module 2 with an oxidizing agent, the reduction step of filtering the reducing agent through the separation membrane module 2 is performed in the present invention.

  Further, as the reduction process, after the back pressure cleaning is completed, the backwash valve 13, the filtration valve 14, the circulation control valve 18, and the circulation return control valve 16 are closed, and the circulation pump 8, the filtration pump 11, and the backwash pump 12 are turned on. Stopping, opening the discharge control valve 15 and the reducing agent supply control valve 19, and operating the reducing agent supply pump 7, causes the fau that has been separated from the surface and pores of the separation membrane and floated in the separation membrane module 2. Ring material is discharged out of the system. After the drainage is completed, the discharge control valve 15 and the reducing agent supply control valve 19 are closed, the circulation control valve 18, the circulation return control valve 16, and the filtration valve 14 are opened, and the circulation pump 8 and the filtration pump 11 are operated to perform filtration. Start.

  In the present invention, if necessary, a bypass line 25 is provided on the secondary side of the separation membrane module 2, and at least a part of the water membrane filtrate containing the reducing agent is discharged out of the system through the bypass line 25. Can do. Here, the bypass line 25 is preferably provided between the separation membrane module 2 and the backwash valve 13 as shown in FIG. The bypass line 25 can also be provided between the separation membrane module 2 and the filtration valve 14. However, in this case, it is necessary to use it in consideration of the concentration of the oxidizing agent remaining in the pipe and the influence of the reducing agent on the filtrate. By providing the bypass line, it becomes possible to discharge a part of the membrane filtrate of the water containing the reducing agent out of the system. It can be adjusted not to enter. If an excessive reducing agent enters the filtrate storage tank, it becomes an impurity of a chemical product obtained by filtration. Therefore, it is necessary to adjust so that the excessive reducing agent does not enter the filtrate storage tank.

  Moreover, in this invention, before or after filtering the water containing a reducing agent as needed, it is used for the liquid and fermentation which contain at least one part of a fermentation raw material from the secondary side of a separation membrane module to the primary side. A liquid containing at least one of the neutralizing agent and a liquid containing at least one of the membrane filtrates can be supplied. For example, after carrying out the reduction step, the filtration valve 14 is opened, and the membrane filtrate stored in the filtrate storage tank 23 is supplied to the separation membrane module 2 using the filtration pump 11. . By this supply, the oxidizing agent and reducing agent remaining in the pipe from the primary side of the separation membrane module to the filtrate storage tank are diluted and given to microorganisms in the culture solution supplied to the primary side of the separation membrane module. Adverse effects can be prevented.

  In the present invention, if necessary, water containing an oxidant is contained in the separation membrane module after performing reverse pressure cleaning for supplying water containing an oxidant from the secondary side to the primary side of the separation membrane module. Can be held for a predetermined time. Since the cleaning of the film surface with the oxidizing agent is affected by the concentration of the oxidizing agent and the contact time with the dirt substance, the membrane cleaning can be performed more effectively by holding the water containing the oxidizing agent for a predetermined time. The holding time can be from 1 second to 10 hours, but is preferably from 20 seconds to 20 minutes. If the holding time is shorter than this, the dirt substance cannot be sufficiently decomposed by the oxidizing agent, and if it is longer than this, the filtration efficiency is lowered and the separation membrane may be adversely affected.

  In the present invention, if necessary, before, during, after, or in the separation membrane module, the back pressure cleaning for supplying water containing the oxidizing agent from the secondary side to the primary side of the separation membrane module is performed. It is also possible to carry out gas cleaning during at least a part of the time during which the water containing the oxidizing agent is retained. By performing gas cleaning, the separation membrane shakes due to gas supply. Due to this shaking, the contaminants on the separation membrane are peeled off from the membrane surface and contacted with the oxidizing agent to be decomposed. The gas supplied to the gas cleaning may be any gas that does not adversely affect the fermentation, and it is desirable to supply the gas after performing filter sterilization or the like in order to prevent contamination by various bacteria. For example, compressed nitrogen can be supplied to the separation membrane module through a commercially available gas sterilization filter.

  Moreover, in this invention, it can concentrate by filtering at least one part of the permeation | transmission liquid containing a chemical using a semipermeable membrane module as needed. When a permeate containing chemicals is filtered using a semipermeable membrane module, water is separated from the semipermeable membrane and the water in the filtrate is reduced, so the permeate containing chemicals can be concentrated. .

  Here, the semipermeable membrane is a membrane having a semipermeable property that allows some components in the mixed liquid to be separated, for example, a solvent to permeate but not other components, and includes a nanofiltration membrane and a reverse osmosis membrane. As the material, polymer materials such as cellulose acetate polymer, polyamide, polyester, polyimide, vinyl polymer are often used. In addition, the membrane structure has a dense layer on at least one side of the membrane, an asymmetric membrane having fine pores gradually increasing from the dense layer to the inside of the membrane or the other side, and another layer on the dense layer of the asymmetric membrane. A composite membrane having a very thin separation functional layer formed of a material can be used. The membrane form includes a hollow fiber membrane and a flat membrane. The present invention can be carried out regardless of the film material, film structure and film form, and any of them is effective, but as typical films, for example, cellulose acetate-based or polyamide-based asymmetric membranes and polyamide-based, There are composite membranes having a urea-based separation functional layer, and it is preferable to use a cellulose acetate-based asymmetric membrane and a polyamide-based composite membrane from the viewpoint of water production, durability, and salt rejection.

  Further, in the present invention, the semipermeable membrane element is formed for practical use of the semipermeable membrane, and the flat membrane is a spiral, tubular, plate-and-frame type element, The hollow fiber membranes can be used after being bundled and incorporated into a case, but the present invention is not dependent on the form of these semipermeable membrane elements.

  Further, in the present invention, the semipermeable membrane module provided with the nanofiltration membrane or the reverse osmosis membrane is not limited to a module in which one or several semipermeable membrane elements are housed in a pressure vessel. This includes those arranged in parallel. The combination, number and arrangement can be adjusted as necessary.

  The backwashing step and the reduction step in the present invention are effective for continuous fermentation over a long period of time. Long-term continuous fermentation is thought to be affected by changes in the microorganism concentration, changes in the concentration of the target product, changes in the concentration of by-products, and changes in the clogging of the separation membrane. It is more effective to maintain the separation membrane so that it does not become clogged than to perform washing such as backwashing after the clogging occurs. Since factors that greatly affect occlusion change, cleaning such as backwashing is necessary.

  In continuous fermentation, membrane clogging mainly due to organic matter is conceivable, so it is necessary to perform backwashing using an oxidizing agent effective for membrane clogging with organic matter. However, when backwashing is performed using an oxidizing agent, membrane cleaning can be performed effectively. However, microorganisms can be decomposed by the oxidizing agent that is put into the separation membrane by backwashing and remains unreacted. In this case, if the microbial decomposition rate by the remaining oxidizing agent is faster than the microbial growth rate in continuous fermentation, the microbial concentration may decrease, and even if there is no decrease in the microbial concentration, the increase rate of the microbial concentration is slow. There is a problem. Since the microbial concentration affects the fermentation rate, a decrease in the microbial concentration is likely to lead to a decrease in the fermentation rate. Therefore, in order to prevent the oxidant from affecting the decrease in the microbial concentration, the separation membrane is effectively washed without affecting the microbial concentration by backwashing with the oxidant and then neutralizing the residual oxidant with the reducing agent. It is possible to perform continuous fermentation over a long period of time.

  As described above, by repeatedly performing the above filtration step, backwashing step, and reduction step, membrane washing can be performed without damaging the fermentation microorganisms, and the adverse effect of the oxidizing agent on the filtrate can be prevented, and filtration can be performed. When the liquid is concentrated with a semipermeable membrane module, the oxidant in the filtrate can prevent the adverse effect of the filtrate on the semipermeable membrane module, and the continuous fermentation method maintains stable and high productivity over a long period of time. A method for producing a chemical product can be provided.

  Hereinafter, in order to describe the present invention in more detail, specific embodiments of continuous fermentation using the apparatus shown in the schematic diagram of FIG. 1 will be described with reference to examples.

Example 1
First, a membrane filtration module was manufactured. The hollow fiber membrane used for the production of the membrane module was dismantled from Toray Industries, Inc., pressurized PVDF hollow fiber membrane module “HFS1020”, and only the unbonded portion was cut out, and the resulting PVDF hollow fiber membrane ( Nominal pore diameter: 0.05 μm) was used. A polycarbonate resin molded product was used as the separation membrane module member. The capacity of the produced membrane filtration module was 40 mL, and the effective filtration area of the membrane filtration module was 260 square cm. Example 1 was performed using the produced porous hollow fiber membrane and membrane filtration module. The operating conditions in Example 1 are as follows unless otherwise specified.
Fermentation tank capacity: 2 (L)
Fermentation culture tank effective volume: 1.5 (L)
Separation membrane used for filtration: 60 polyvinylidene fluoride hollow fiber membranes Temperature control: 37 (° C)
Aeration volume of fermentation culture tank: 0.1 (L / min)
Fermentation tank agitation speed: 600 (rpm)
pH adjustment: Adjusted to pH 6 with 3N NaOH Lactic acid fermentation medium supply rate: Variable in the range of 15 to 300 mL / hr Circulating fluid volume by culture fluid circulation device: 4.2 (L / min)
Membrane filtration flow rate control: flow rate control by suction pump The medium was used after autoclaving (121 ° C, 15 minutes). Sporolactobacillus laevolacticus JCM2513 (SL strain) is used as the microorganism, the lactic acid fermentation medium having the composition shown in Table 1 is used as the medium, and the concentration of the product lactic acid is evaluated using the HPLC shown below under the following conditions: I went there.

Column: Shim-Pack SPR-H (manufactured by Shimadzu Corporation)
Mobile phase: 5 mM p-toluenesulfonic acid (0.8 mL / min)
Reaction phase: 5 mM p-toluenesulfonic acid, 20 mM Bistris, 0.1 mM EDTA · 2Na (0.8 mL / min)
Detection method: Electrical conductivity Column temperature: 45 ° C
The optical purity of lactic acid was analyzed under the following conditions.
Column: TSK-gel Enantio L1 (manufactured by Tosoh Corporation)
Mobile phase: 1 mM aqueous copper sulfate flow rate: 1.0 mL / min Detection method: UV 254 nm
Temperature: 30 ° C
The optical purity of L-lactic acid is calculated by the following formula (i).
Optical purity (%) = 100 × (LD) / (D + L) (i)
Further, the optical purity of D-lactic acid is calculated by the following formula (ii).
Optical purity (%) = 100 × (DL) / (D + L) (ii)
Here, L represents the concentration of L-lactic acid, and D represents the concentration of D-lactic acid.

  For the culture, the SL strain was first cultured overnight in a test tube with 5 mL of lactic acid fermentation medium (pre-culture). The obtained culture solution was inoculated into 100 mL of a fresh lactic acid fermentation medium, and cultured with shaking in a 500 mL Sakaguchi flask at 30 ° C. for 24 hours (pre-culture). Pre-culture medium is inoculated by placing the medium in the 1.5 L fermentation culture tank of the continuous fermentation apparatus shown in Fig. 1 and stirred with the attached stirring apparatus 4, adjusting the aeration volume of the fermentation culture tank 1 and adjusting the temperature Then, the pH was adjusted, and the culture was performed for 50 hours without operating the circulation pump 8 (pre-culture). Immediately after completion of the pre-culture, the circulating pump 8 is operated, the lactic acid fermentation medium is continuously supplied in addition to the operating conditions at the time of pre-culture, and the amount of the permeate through the membrane is 1.5 L Then, continuous culture was performed, and D-lactic acid was produced by continuous fermentation. Control of the amount of permeated water through the continuous fermentation test was carried out by measuring the amount of filtration coming out of the filtration pump 11 and changing it under membrane filtration rate control conditions. The produced D-lactic acid concentration and optical purity in the membrane filtration culture solution were appropriately measured.

  The membrane filtration operation of continuous fermentation was performed from 50 hours to 500 hours, and was performed together with the backwashing step and the reduction step. The filtration step, backwashing step, and reduction step were performed by 8 minute filtration, 1 minute backwashing, and 1 minute reduction, respectively, and the above steps were repeated.

  In the filtration process, using the control device, the reducing agent supply control valve 19, the discharge control valve 15 and the backwash valve 13 are closed, the reducing agent supply pump 7 and the backwash pump 12 are stopped, and the circulation return control valve 16 and filtration are performed. The valve 14 was opened and the filtration pump 11 was used. The filtration flow rate was 0 to 50 hours, and filtration was performed at a flow rate of 100 mL / h until 50 to 500 hours.

  The backwashing process was performed for 50 to 500 hours, and after the filtration process for 8 minutes, backwashing was performed for 1 minute. The chemical solution used for back pressure washing was diluted with distilled water using a commercially available sodium hypochlorite having an effective chlorine concentration of 10% so that the free chlorine concentration was 1,000 ppm. In the backwashing process, the circulation control valve 18, the reducing agent supply control valve 19, the discharge control valve 15 and the filtration valve 14 are closed using the control device, the reducing agent supply pump 7 and the filtration pump 11 are stopped, and the circulation return control is performed. Open the valve 16 and the backwash valve 13 and start the backwash pump 12, and the backwash flow rate is 0 to 50 hours without filtration, and 50 to 500 hours at 200 mL / h. It was.

  The reduction process was performed for a filtration time of 50 to 500 hours, followed by filtration for 8 minutes and backwashing for 1 minute, followed by a reduction process for 1 minute. The chemical solution used in the reduction process was diluted with distilled water to a concentration of 30 ppm using 35% strength commercially available sodium hydrogen sulfite.

  In the reduction step, the circulation control valve 18, the gas supply valve 17, the filtration valve 14 and the backwash valve 13 are closed, the circulation pump 8, the gas supply device 22, the filtration pump 11 and the backwash pump 12 are stopped, and then the reducing agent The operation was performed by opening the supply control valve 19 and the discharge control valve 15 and starting the reducing agent supply pump 7. At this time, the circulation return valve was closed several seconds after the supply of the reducing agent so that the separation membrane module could be vented, and then pressure was applied to the separation membrane module. The reducing agent supply flow rate was 300 mL / min.

  The filtration differential pressure was measured once / day using a differential pressure gauge, and the microorganism concentration was measured once / day using OD600. To measure OD600, first collect a sample from the fermenter, dilute the sample with distilled water so that the OD600 of the sample is around 1, then measure the absorbance at a wavelength of 600 nm using an absorptiometer (Shimadzu UV-2450). And measured. The obtained measured value was multiplied by the magnification diluted with distilled water, and calculated as the OD600 of the sample.

  The obtained bacterial cell concentration, D-lactic acid production rate, and transmembrane pressure are shown in FIGS. 2, 3 and 4, respectively. As a result, the transmembrane pressure difference could be stably maintained, and a high bacterial cell concentration and D-lactic acid production rate could be obtained.

Comparative Example 1
The same operation as in Example 1 was performed except that water was used instead of sodium hypochlorite and sodium bisulfite in the backwashing step and the reduction step. The obtained bacterial cell concentration, D-lactic acid production rate, and transmembrane pressure are shown in FIGS. 2, 3 and 4, respectively. As a result, the transmembrane pressure difference increased and stable filtration operation could not be performed.

Comparative Example 2
In the reduction step, the same operation as in Example 1 was performed except that water was used instead of sodium bisulfite. The obtained bacterial cell concentration, D-lactic acid production rate, and transmembrane pressure are shown in FIGS. 2, 3 and 4, respectively. As a result, the bacterial cell concentration and the production rate of D-lactic acid decreased, and high-efficiency continuous fermentation operation was not possible.

  According to the present invention, the filterability of the separation membrane can be stabilized over a long period of time, and further, the fermentation performance can be enhanced. In the fermentation industry, chemical products that are fermentation products can be stably produced at low cost. It becomes possible to produce.

DESCRIPTION OF SYMBOLS 1 Fermenter 2 Separation membrane module 3 Temperature control device 4 Stirring device 5 pH sensor / control device 6 Level sensor / control device 7 Reducing agent supply pump 8 Circulating pump 9 Medium supply pump 10 Neutralizing agent supply pump 11 Filtration pump 12 Backwash Pump 13 Backwash valve 14 Filtration valve 15 Discharge control valve 16 Circulation return control valve 17 Module gas supply control valve 18 Circulation control valve 19 Reducing agent supply control valve 20 Reducing agent tank 21 Fermenter gas supply device 22 Module gas supply device 23 Filtration Liquid storage tank 24 Oxidant tank 25 Bypass line

Claims (10)

Permeate containing chemicals while continuously introducing the fermentation raw material into the fermenter, filtering the culture solution containing microorganisms and chemicals using a separation membrane module, and continuously holding the non-permeate in the fermentor A separation membrane module cleaning method in continuous fermentation, in which reverse pressure cleaning is performed to supply water containing an oxidizing agent from the secondary side to the primary side of the separation membrane module, and then the reducing agent is removed by the separation membrane module. A method for washing a separation membrane module for continuous fermentation, characterized by filtering the water contained therein. The separation membrane for continuous fermentation according to claim 1, wherein at least part of the water membrane filtrate containing the reducing agent is discharged out of the system from a bypass line provided on the secondary side of the separation membrane module. How to clean the module. Before or after filtering water containing the reducing agent, from the secondary side to the primary side of the separation membrane module, a liquid containing at least part of the fermentation raw material, a liquid containing at least part of the neutralizing agent used for fermentation, and a membrane The method for cleaning a separation membrane module for continuous fermentation according to claim 1 or 2, wherein a liquid containing at least one selected from the group consisting of filtrates is supplied. The water containing an oxidant is retained in the separation membrane module for a predetermined time after performing the reverse pressure cleaning in which the water containing the oxidant is supplied from the secondary side to the primary side of the separation membrane module. The washing | cleaning method of the separation membrane module for continuous fermentation in any one of claim | item 1-3. Before, during, or after back pressure cleaning for supplying water containing an oxidant from the secondary side to the primary side of the separation membrane module, or when the water containing the oxidant is held in the separation membrane module The method for cleaning a separation membrane module for continuous fermentation according to any one of claims 1 to 4, wherein gas cleaning is performed on at least a part of the continuous membrane. The method for cleaning a separation membrane module for continuous fermentation according to any one of claims 1 to 5, wherein at least a part of the permeate containing a chemical is filtered through a semipermeable membrane. Fermenter into which fermentation raw materials are continuously introduced, a separation membrane module that filters and separates a culture solution containing microorganisms and chemicals into permeate and non-permeate containing chemicals, and culture from the fermenter to the separation membrane module A culture solution supply means for supplying a solution, a non-permeate supply means for supplying a non-permeate to the fermenter from the separation membrane module, and water containing an oxidant from the secondary side to the primary side of the separation membrane module A membrane separation apparatus for continuous fermentation, comprising: an oxidant supply means; and a reducing agent supply means for supplying water containing a reducing agent to the primary side of the separation membrane module. The membrane separation apparatus for continuous fermentation according to claim 7, comprising a bypass line that communicates the secondary side of the separation membrane module with outside the system. 9. The continuous fermentation membrane separator according to claim 7, wherein gas is supplied to a pipe from the fermenter to the separation membrane module and / or a lower portion of the separation membrane module. The membrane separator for continuous fermentation according to any one of claims 7 to 9, comprising a semipermeable membrane module for filtering at least a part of the membrane filtrate.

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