Reaction device and method for producing product

Abstract

The present disclosure provides technology which is useful in terms of increasing the speed of a process for continuously activating a coenzyme to cause a plurality of types of enzyme reactions. The present disclosure provides a reaction device (1a) wherein a first enzyme reaction vessel (10a), a first electrochemical reaction vessel (20a), a second enzyme reaction vessel (10b), and a second electrochemical reaction vessel (20b) are disposed such that a reaction solution (R) passes and circulates therethrough in a specific order. The reaction solution (R) contains a first substrate, a second substrate, and a coenzyme. The first substrate is oxidized or reduced by a first enzyme (15a). The second substrate is oxidized or reduced by a second enzyme (15b). The first enzyme (15a) is stored inside the first enzyme reaction vessel (10a). The second enzyme (15b) is stored inside the second enzyme reaction vessel (10b). The first electrochemical reaction vessel (20a) and the second electrochemical reaction vessel (20b) electrochemically restore the activity of the coenzyme.

Description

Reactor and method for producing product

[0001] The present disclosure relates to a reactor and a method for producing a product.

[0002] Enzymes are traditionally known as one of the catalysts in living organisms, and a substrate is converted into a product, which is a chemically different substance, by the catalytic action of the enzyme.

[0003] An example of an enzymatic reaction is an enzymatic reaction using glucose dehydrogenase. This enzymatic reaction requires a substrate, glucose, and a coenzyme, nicotinamide adenine dinucleotide (NAD). In this enzymatic reaction, the substrate is converted into gluconolactone, and the coenzyme is converted into reduced nicotinamide adenine dinucleotide (NADH).

[0004] For example, Patent Document 1 describes an electrochemical reaction device that contains glucose dehydrogenase and NAD and includes a first tank in which a working electrode is placed, and a second tank in which a counter electrode is placed. In this electrochemical reaction device, glucose dehydrogenase functions as a catalyst, and NAD participates as a coenzyme to cause an enzyme reaction. In addition, when a voltage is applied between the working electrode and the counter electrode, NADH produced by the enzyme reaction is oxidized to produce oxidized nicotinamide adenine dinucleotide (NADH). + In this way, NAD is regenerated by applying a voltage between the working electrode and the counter electrode, and glucose decomposition can continue even if the liquid in the first tank does not contain a large amount of NAD.

[0005] Patent Document 2 describes an enzyme reaction apparatus. This enzyme reaction apparatus includes a cylindrical container and a separation membrane. An immobilized enzyme is supported on the inner wall surface of the cylindrical container. In the immobilized enzyme, the enzyme is immobilized on water-dispersible high molecular weight polymer particles. The separation membrane does not allow the immobilized enzyme to pass through, but allows the enzyme reaction product to pass through.

[0006] Patent Document 3 describes an enzyme reaction apparatus. This enzyme reaction apparatus includes a reactor, multiple adsorbers, a desorption liquid supply system, a coenzyme supply system, and a reaction liquid discharge system. The adsorbers recover the coenzyme from the reaction liquid produced in the reactor. The desorption liquid supply system supplies the adsorbers with a desorption liquid to desorb the coenzyme from the adsorbent. This allows the coenzyme to be reused.

[0007] International Publication No. 2023 / 074453 Japanese Patent Application Laid-Open No. 60-27380 Japanese Patent Application Laid-Open No. 61-205499

[0008] The techniques described in the above patent documents have room for reexamination from the viewpoint of increasing the speed of a process in which a coenzyme is successively activated to cause multiple types of enzymatic reactions. Therefore, the present disclosure provides a technique that is advantageous from the viewpoint of increasing the speed of a process in which a coenzyme is successively activated to cause multiple types of enzymatic reactions.

[0009] The present disclosure provides a catalytic converter comprising: a first enzyme reactor; a first electrochemical reactor; a second enzyme reactor; a second electrochemical reactor; a first enzyme disposed inside the first enzyme reactor; and a second enzyme disposed inside the second enzyme reactor, wherein the first enzyme reactor, the first electrochemical reactor, the second enzyme reactor, and the second electrochemical reactor are arranged so that a reaction solution passes through and circulates through the first electrochemical reactor, the first enzyme reactor, the second electrochemical reactor, and the second enzyme reactor in that order, wherein the reaction solution includes a first substrate to be oxidized or reduced by the first enzyme, a second substrate to be oxidized or reduced by the second enzyme, and a coenzyme that restores the activity of the first enzyme after reacting with the first substrate and the activity of the second enzyme after reacting with the second substrate, wherein the first enzyme remains inside the first enzyme reactor when the reaction solution passes through the first enzyme reactor, and the second enzyme remains inside the second enzyme reactor when the reaction solution passes through the second enzyme reactor, The first electrochemical reactor and the second electrochemical reactor provide a reactor for electrochemically restoring the activity of the coenzyme.

[0010] The reaction apparatus of the present disclosure is advantageous from the viewpoint of increasing the speed of the process in which coenzymes are successively activated to cause multiple types of enzymatic reactions.

[0011] Fig. 1 is a diagram schematically showing an example of a reaction apparatus according to an embodiment. Fig. 2 is a diagram schematically showing an example of a unit including an enzyme reactor and an electrochemical reactor in a reaction apparatus according to an embodiment. Fig. 3 is a flowchart showing an example of a method for producing a product according to an embodiment. Fig. 4 is a diagram showing yet another example of a reaction apparatus according to an embodiment. Fig. 5 is a diagram showing yet another example of a reaction apparatus according to an embodiment. Fig. 6 is a diagram showing yet another example of a reaction apparatus according to an embodiment. Fig. 7 is a diagram showing yet another example of a reaction apparatus according to an embodiment. Fig. 8 is a diagram showing yet another example of a reaction apparatus according to an embodiment.

[0012] (Findings that form the basis of the present disclosure) As described in Patent Document 1, the coenzyme can be regenerated by applying a voltage between the working electrode and the counter electrode, and the coenzyme can be repeatedly used for the enzyme reaction. On the other hand, when the enzyme is affected by the electric field generated by applying a voltage between the working electrode and the counter electrode, the enzyme deteriorates, making it difficult to repeatedly use the enzyme.

[0013] Therefore, the present inventors have conducted extensive research into the configuration of a reaction device that is advantageous from the viewpoint of continuously activating a coenzyme while suppressing enzyme degradation. As a result, it has been newly discovered that a reaction device equipped with a predetermined enzyme reactor and an electrochemical reactor can continuously activate a coenzyme while suppressing enzyme degradation. On the other hand, it has been newly discovered that when such a reaction device is equipped with only one enzyme reactor and one electrochemical reactor, it is difficult to increase the speed of the process in which a coenzyme is continuously activated to cause multiple types of enzymatic reactions. Therefore, the present inventors have further improved such a reaction device to increase the processing speed, and have completed the reaction device of the present disclosure. In this disclosure, "continuously" means "repeatedly."

[0014] (Embodiments of the Present Disclosure) Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. Note that the embodiments described below are all comprehensive or specific examples. The numerical values, shapes, materials, components, the arrangement and connection of the components, steps, and the order of steps shown in the following embodiments are merely examples and are not intended to limit the scope of the claims. Furthermore, each drawing is not necessarily an exact illustration. In each drawing, substantially identical configurations are assigned the same reference numerals, and redundant explanations may be omitted or simplified. Furthermore, below, terms indicating the relationship between elements, such as "parallel" and "perpendicular," terms indicating the shape of elements, such as "rectangular," and numerical ranges do not only indicate the strict meaning, but also include substantially equivalent ranges, for example, differences of a few percent. These embodiments shown as comprehensive or specific examples may be realized using a system, an apparatus, an integrated circuit, a computer program, or a computer-readable recording medium such as a CD-ROM, or may be realized using any combination of a system, a method, an integrated circuit, a computer program, and a recording medium.

[0015] (Embodiment) Hereinafter, an embodiment will be specifically described with reference to FIGS. 1 to 8. FIG.

[0016] FIG. 1 is a schematic diagram illustrating an example of a reaction apparatus according to an embodiment. As shown in FIG. 1, the reaction apparatus 1a includes a first enzyme reactor 10a, a first electrochemical reactor 20a, a second enzyme reactor 10b, a second electrochemical reactor 20b, a first enzyme 15a, and a second enzyme 15b. The first enzyme 15a is disposed inside the first enzyme reactor 10a. The second enzyme 15b is disposed inside the second enzyme reactor 10b. The first enzyme reactor 10a, the first electrochemical reactor 20a, the second enzyme reactor 10b, and the second electrochemical reactor 20b are arranged so that the reaction solution R passes through and circulates through them in a specific order. The specific order is the first electrochemical reactor 20a, the first enzyme reactor 10a, the second electrochemical reactor 20b, and the second enzyme reactor 10b. The reaction solution R contains a first substrate, a second substrate, and a coenzyme. The reaction solution R may contain, for example, a solvent such as water, a buffer such as Good's buffer, a salt such as sodium chloride, and a pH adjuster such as hydrochloric acid, as necessary. The first enzyme 15a and the second enzyme 15b are, for example, different types of oxidoreductases. The first substrate is oxidized or reduced by the first enzyme 15a. The second substrate is oxidized or reduced by the second enzyme 15b. The combination of the first substrate and the second substrate may be a combination of sugars such as fructose and glucose, or a combination of proteins such as ovomucoid and casein. For example, a mixture of egg white and a dairy product may contain ovomucoid and casein. The reaction solution R may be prepared, for example, by adding a coenzyme and other components to a mixture of egg white and a dairy product. The coenzyme restores the activity of the first enzyme 15a after reaction with the first substrate and the activity of the second enzyme 15b after reaction with the second substrate. Examples of coenzymes include NAD and nicotinamide adenine dinucleotide phosphate (NADP). The coenzyme that restores the activity of the first enzyme 15a and the coenzyme that restores the activity of the second enzyme 15b may be the same or different. Therefore, the reaction solution R may contain only a single type of coenzyme or may contain multiple types of coenzymes. The first enzyme 15a is arranged so as to remain inside the first enzyme reactor 10a when the reaction solution R passes through the first enzyme reactor 10a.The second enzyme 15b is arranged so as to remain inside the second enzyme reactor 10b when the reaction solution R passes through the second enzyme reactor 10b. The first electrochemical reactor 20a and the second electrochemical reactor 20b electrochemically restore the activity of the coenzyme contained in the reaction solution R.

[0017] In the reaction device 1a, the reaction solution R circulates by passing through the first electrochemical reactor 20a, the first enzyme reactor 10a, the second electrochemical reactor 20b, and the second enzyme reactor 10b in this order. This allows the coenzymes contained in the reaction solution R to be continuously activated by the first electrochemical reactor 20a and the second electrochemical reactor 20b. In addition, since the first enzyme 15a remains inside the first enzyme reactor 10a and the second enzyme reactor 15b remains inside the second enzyme reactor 10b, the first enzyme 15a and the second enzyme 15b are not affected by the first electrochemical reactor 20a and the second electrochemical reactor 20b, and deterioration of the first enzyme 15a and the second enzyme 15b can be suppressed. Therefore, the first enzyme 15a and the second enzyme 15b can be repeatedly used. The reaction solution R containing the first substrate and the second substrate circulates by passing through multiple electrochemical reactors, the first enzyme reactor 10a, and the second enzyme reactor 10b. Therefore, multiple types of enzyme reactions can occur simultaneously in the reaction device 1a, and the speed of processing requiring multiple types of enzyme reactions tends to increase.

[0018] 1, for example, the first enzyme reactor 10a and the first electrochemical reactor 20a form a first unit 5a. In addition, the second enzyme reactor 10b and the second electrochemical reactor 20b form a second unit 5b. With this configuration, the reaction device 1a can be easily assembled. The first enzyme reactor 10a and the first electrochemical reactor 20a do not have to form a unit, and the second enzyme reactor 10b and the second electrochemical reactor 20b do not have to form a unit.

[0019] 1, the reaction apparatus 1a includes, for example, a storage tank 40, an agitator 41, and a motor 42. A reaction liquid R is stored inside the storage tank 40. The agitator 41 and the motor 42 are connected, and the agitator 41 is rotated by the motor 42. The agitator 41 is disposed inside the storage tank 40, and the reaction liquid R is agitated by the rotation of the agitator 41. The agitator 41 may be configured as a magnetic stirrer.

[0020] The reaction apparatus 1a includes, for example, a flow path 32a, a valve 31v, a flow path 32b, a flow path 32c, a flow path 32d, a flow path 32e, and a pump 36. The flow path 32a connects the reservoir 40 and the first electrochemical reactor 20a. The valve 31v is disposed in the flow path 32a. The flow path 32b connects the first electrochemical reactor 20a and the first enzyme reactor 10a. The flow path 32c connects the first enzyme reactor 10a and the second electrochemical reactor 20b. The flow path 32d connects the second electrochemical reactor 20b and the second enzyme reactor 10b. The flow path 32e connects the second enzyme reactor 10b and the reservoir 40. The pump 36 is disposed in, for example, the flow path 32e. The pump 36 may be disposed in the flow path 32a or the flow path 32c.

[0021] For example, the pump 36 is operated with the valve 31v open, whereby the reaction solution R passes through the flow path 32a, the first electrochemical reactor 20a, the flow path 32b, the first enzyme reactor 10a, the flow path 32c, the second electrochemical reactor 20b, the flow path 32d, the second enzyme reactor 10b, and the flow path 32e, and returns to the storage tank 40. In this way, the reaction solution R circulates, passing through the first enzyme reactor 10a, the first electrochemical reactor 20a, the second enzyme reactor 10b, and the second electrochemical reactor 20b in a specific order.

[0022] The reaction apparatus 1a includes, for example, a pH meter 43, a pH measurement electrode 43e, a signal line 43s, a supply device 50, a path 52, and a valve 52v. The pH meter 43 measures the pH of the liquid to be measured based on the potential difference between the reference electrode and the glass electrode in the pH measurement electrode 43e. The pH measurement electrode 43e is immersed in the reaction liquid R stored inside the storage tank 40. Therefore, the pH of the reaction liquid R is measured by the pH meter 43.

[0023] The supplier 50 is connected to the reservoir 40 via a path 52 and supplies a pH adjuster toward the reservoir 40. A valve 52v is disposed on the path 52. A signal for controlling the opening and closing of the valve 52v is sent to the valve 52v through a signal line 43s. This controls the opening and closing of the valve 52v. Examples of pH adjusters are hydrochloric acid, sodium hydroxide, and malic acid.

[0024] The first electrochemical reactor 20a and the second electrochemical reactor 20b are not limited to a specific configuration as long as they can electrochemically restore the activity of the coenzyme. FIG. 2 is a schematic diagram illustrating an example of a unit including an enzyme reactor and an electrochemical reactor in a reaction device according to an embodiment. As shown in FIG. 2, each of the first electrochemical reactor 20a and the second electrochemical reactor 20b includes, for example, a first chamber 21, a second chamber 22, a membrane 23, and a voltage application device 26. The reaction solution R passes through the first chamber 21. For example, a flow path 32a is connected to the first chamber 21 of the first electrochemical reactor 20a, and a flow path 32c is connected to the first chamber 21 of the second electrochemical reactor 20b. A working electrode 25a is disposed in the first chamber 21. A counter electrode 25b is disposed in the second chamber 22. The membrane 23 separates the first chamber 21 from the second chamber 22. The membrane 23 has ion conductivity and prevents permeation of the coenzyme, the first substrate, and the second substrate contained in the reaction solution R. The voltage application device 26 is a device for applying a voltage between the working electrode 25 a and the counter electrode 25 b.

[0025] When a voltage is applied between the working electrode 25a and the counter electrode 25b by the voltage application device 26, an oxidation-reduction reaction occurs at the working electrode 25a and the counter electrode 25b, and the coenzyme is activated. +is reduced to produce NADH.

[0026] 2, the first chamber 21 and the second chamber 22 contain an electrolyte solution E. This facilitates a predetermined oxidation-reduction reaction at the working electrode 25a and the counter electrode 25b. Examples of electrolytes used in the electrolyte solution E include sodium chloride and potassium chloride. For example, the electrolyte solution E contained in the second chamber 22 does not contain a substrate or a coenzyme.

[0027] The membrane 23 is not limited to a specific membrane as long as it prevents the permeation of the coenzyme, the first substrate, and the second substrate and has ion conductivity. The membrane 23 may contain, for example, a polymer having a perfluoro side chain containing a sulfonic acid group. This configuration allows certain ions such as protons to move quickly through the membrane 23, and the oxidation-reduction reaction for activating the coenzyme can be efficiently carried out at the working electrode 25 a and the counter electrode 25 b.

[0028] The materials forming the surfaces of the working electrode 25a and the counter electrode 25b are not limited to specific materials. The surfaces of the working electrode 25a and the counter electrode 25b include, for example, a conductive material. The conductive material is, for example, a material that does not decompose when the conductive material is oxidized. Examples of conductive materials include carbon materials, conductive polymers, semiconductor materials, and metal materials. Examples of carbon materials include carbon nanotubes, Ketjen Black (registered trademark), glassy carbon, graphene, fullerene, carbon fiber, carbon fabric, and carbon aerogel. Examples of conductive polymers include polyaniline, polyacetylene, polypyrrole, poly(3,4-ethylenedioxythiophene), poly(p-phenylenevinylene), polythiophene, and poly(p-phenylene sulfide). Examples of semiconductor materials include silicon, germanium, indium tin oxide (ITO), titanium oxide, copper oxide, and silver oxide. Examples of metallic materials include gold, platinum, silver, titanium, aluminum, tungsten, copper, iron, and palladium. The working electrode 25a may be a glassy carbon electrode, and the counter electrode 25b may be a platinum electrode.

[0029] The surface area of ​​the counter electrode 25b is, for example, larger than the surface area of ​​the working electrode 25a.

[0030] 2, for example, a reference electrode 25c is disposed in the first chamber 21. The reference electrode 25c makes it easy to stabilize the potential difference between the working electrode 25a and the counter electrode 25b. The reference electrode 25c is, for example, a silver / silver chloride electrode.

[0031] The first enzyme reactor 10a and the second enzyme reactor 10b are not limited to a specific configuration as long as the first enzyme 15a or the second enzyme 15b is disposed therein and the first enzyme 15a or the second enzyme 15b remains therein. Each of the first enzyme reactor 10a and the second enzyme reactor 10b is, for example, a tubular reactor. A reaction solution R is supplied to each of the first enzyme reactor 10a and the second enzyme reactor 10b so as to pass through them in the direction opposite to the direction of gravity, for example.

[0032] As shown in FIG. 2 , for example, the first enzyme reactor 10a has a first filter 11a, and the second enzyme reactor 10a has a second filter 11b. When the reaction solution R passes through the first enzyme reactor 10a, the first filter 11a allows the coenzyme, the first substrate, and the second substrate to pass through, but prevents the first enzyme 15a from passing through. When the reaction solution R passes through the second enzyme reactor 10b, the second filter 11b allows the coenzyme, the first substrate, and the second substrate to pass through, but prevents the second enzyme 15a from passing through. As a result, the first enzyme 15a and the second enzyme 15b remain inside the first enzyme reactor 10a and the second enzyme reactor 10b, and the coenzyme, the first substrate, and the second substrate are removed from the insides of the first enzyme reactor 10a and the second enzyme reactor 10b. The first filter 11a and the second filter 11b each allow the permeation of, for example, products produced by the enzymatic reactions involving the first enzyme 15a and the second enzyme 15b. In this case, the product obtained by the enzymatic reaction can be easily recovered.

[0033] The first enzyme reactor 10a is equipped with, for example, a pair of first filters 11a. The second enzyme reactor 10b is equipped with, for example, a pair of second filters 11b. The first filters 11a are disposed, for example, at the inlet and outlet of the first enzyme reactor 10a in the flow of the reaction solution R. The second filters 11b are disposed, for example, at the inlet and outlet of the second enzyme reactor 10b in the flow of the reaction solution R.

[0034] Each of the first filter 11a and the second filter 11b is, for example, a porous membrane or a fiber-containing membrane having a predetermined average pore size. The average pore size of each of the first filter 11a and the second filter 11b is not limited to a specific value as long as it allows the coenzyme, the first substrate, and the second substrate to pass through while preventing the first enzyme 15a or the second enzyme 15b from passing through. As described below, for example, when the first enzyme 15a and the second enzyme 15b are supported on the surface of carrier particles, the average pore size of the filter 11 is, for example, smaller than half the average particle size of the carrier particles. In this case, it is easier to prevent the first enzyme 15a and the second enzyme 15b from passing through while allowing the coenzyme and the substrate to pass through. The average pore size of the first filter 11a and the second filter 11b can be determined, for example, by gas adsorption.

[0035] Each of the first enzyme 15a and the second enzyme 15b is supported on the surface of a carrier particle, for example. In this case, the first enzyme 15a or the second enzyme 15b can be more easily retained inside the first enzyme reactor 10a or the second enzyme reactor 10b when the reaction solution R passes through them. Each of the first enzyme 15a and the second enzyme 15b may be disposed alone in the first enzyme reactor 10a without being supported on a carrier, or the second enzyme 15b may be disposed alone in the second enzyme reactor 10b.

[0036] The carrier particles are not limited to specific particles as long as they can support the first enzyme 15a or the second enzyme 15b on their surfaces. The carrier particles include, for example, an organic polymer or a non-metallic inorganic material. In this case, the activity of the first enzyme 15a or the second enzyme 15b is likely to be maintained at a high level, and the first enzyme 15a or the second enzyme 15b can be easily used repeatedly. An example of an organic polymer is an ion exchange resin. The organic polymer has, for example, a sulfonic acid group. The non-metallic inorganic material includes inorganic materials such as glass and ceramics, but does not include metals.

[0037] The average particle size of the carrier particles is not limited to a specific value. The carrier particles have an average particle size of, for example, 1 micrometer to 5 millimeters. In this case, the first enzyme 15a or the second enzyme 15b can be more easily retained inside the first enzyme reactor 10a or the second enzyme reactor 10b when the reaction solution R passes through them. In addition, the amount of the first enzyme 15a filled in the first enzyme reactor 10a or the amount of the second enzyme 15b filled in the second enzyme reactor 10b is likely to be large. The average particle size of the carrier particles is, for example, the median diameter in a particle size distribution based on the number of particles.

[0038] Examples of combinations of the first and second enzymes are shown in Table 1. For example, in the first example combination, alcohol dehydrogenase is used as the first enzyme and acetaldehyde dehydrogenase is used as the second enzyme. In this case, the first substrate is ethanol, the second substrate is acetaldehyde, and the final product is acetic acid.

[0039] In the present disclosure, the reactor may further include a third enzyme reactor and a third electrochemical reactor, and may be configured as described in (Appendix) (Technology 12) below. Examples of combinations of the first enzyme, second enzyme, and third enzyme in this case are shown in Table 2. For example, in the first example combination, pepsin is used as the first enzyme, trypsin as the second enzyme, and dipeptidase as the third enzyme. In this case, the first substrate is a protein, the second substrate is a peptone, and the third substrate is a peptide, and the final product is an amino acid.

[0040] A product can be produced using the above-described reaction apparatus 1a. The method for producing a product includes passing a reaction solution R containing a first substrate, a second substrate, and a coenzyme through the first electrochemical reactor 20a, the first enzyme reactor 10a, the second electrochemical reactor 20b, and the second enzyme reactor 10b in this order. This allows different enzyme reactions to occur continuously in the first enzyme reactor 10a and the second enzyme reactor 10b. In addition, the activity of the coenzyme can be electrochemically restored in the first electrochemical reactor 20a and the second electrochemical reactor 20b. As described above, the first enzyme 15a remains inside the first enzyme reactor 10a when the reaction solution R passes through the first enzyme reactor 10a. In addition, the second enzyme 15b remains inside the second enzyme reactor 10b when the reaction solution R passes through the second enzyme reactor 10b.

[0041] FIG. 3 is a flowchart showing an example of a method for producing a product. As shown in FIG. 3, in step S101, a reaction solution R is prepared. For example, with the valve 31v closed, a first substrate, a second substrate, and a coenzyme are added to the storage tank 40 so as to have predetermined concentrations, thereby preparing the reaction solution R. Next, in step S102, the valve 31v is opened, and a voltage is applied between the working electrode 25a and the counter electrode 25b by the voltage application device 26 in the first electrochemical reactor 20a and the second electrochemical reactor 20b. In addition, the pump 36 is started to operate. As a result, the reaction solution R in the storage tank 40 passes through the first electrochemical reactor 20a, the first enzyme reactor 10a, the second electrochemical reactor 20b, and the second enzyme reactor 10b and is returned to the storage tank 40. In this manner, the reaction solution R circulates in the reaction device 1a.

[0042] In the first enzyme reactor 10a, the first substrate is oxidized or reduced by the catalytic action of the first enzyme 15a to produce a product. Additionally, in the second enzyme reactor 10a, the second substrate is oxidized or reduced by the catalytic action of the first enzyme 15a to produce another product. As a result, the first enzyme 15a and the second enzyme 15b are rendered inactive, but the activity of the first enzyme 15a and the second enzyme 15b is restored by the action of the coenzyme contained in the reaction solution R. Meanwhile, the coenzyme that restored the activity of the first enzyme 15a or the second enzyme 15b temporarily loses its activity, but the activity of the coenzyme is electrochemically restored in the first electrochemical reactor 20a or the second electrochemical reactor 20b. Therefore, products are continuously produced by the enzyme reactions involving the first enzyme 15a and the second enzyme 15b.

[0043] Next, in step S103, the pH of the reaction solution R in the storage tank 40 is measured by the pH meter 43. Next, in step S104, it is determined whether the pH of the reaction solution R is within a predetermined range. For example, the optimum pH of the enzymatic reaction involving the first enzyme 15a and the enzymatic reaction involving the second enzyme 15b falls within this predetermined range.

[0044] If the result of the determination in step S104 is negative, the process proceeds to step S108, where the amount of pH adjuster to be added to the reaction solution R is calculated. In this calculation, for example, the amount of pH adjuster to be added is determined based on the difference between the measured pH of the reaction solution R and the value corresponding to the above-mentioned optimal pH. For example, the larger this difference, the larger the amount of pH adjuster to be added. Next, the process proceeds to step S109, where the pH adjuster is added. For example, a control signal to open valve 52v is sent from signal line 43s, opening valve 52v, and an amount of pH adjuster corresponding to the calculation result in step S108 is supplied to storage tank 40 from supplier 50 via path 52. In this way, the pH of reaction solution R is adjusted to the above-mentioned optimal pH or a value close to the optimal pH.

[0045] If the determination result in step S104 is positive, or if step S109 is completed, the process proceeds to step S105, and after a predetermined period of time has elapsed, the process proceeds to step S106. The predetermined period of time is set, for example, so that the pH of the reaction solution R falls within a predetermined range in about 10 minutes. A determination is made as to whether a specific time (e.g., 4 hours) has elapsed since the start of operation of the pump 36. If the result of this determination is negative, the process returns to step S103; if the result of this determination is positive, the process proceeds to step S107, where the liquid containing the product is recovered, and production of the product is completed.

[0046] 3 may be automatically controlled using a digital computer having a memory storing a program for executing the process and a processor that reads the program and performs calculations. In this automatic control, the types of the first substrate, the second substrate, and the coenzyme, the volume of the reaction solution R, the type of the working electrode 25a, the voltage applied between the working electrode 25a and the counter electrode 25b, the optimal pH of the enzymes involved in the first enzyme 15a and the second enzyme 15b, and the overall processing time may be used as input parameters.

[0047] The reactor 1a can be modified in various respects. The reactor 1a may include three or more enzyme reactors and three or more electrochemical reactors. In this case, the enzyme reactors and the electrochemical reactors may be arranged alternately in the flow direction of the reaction solution R.

[0048] The reaction device 1a may be arranged such that the reaction solution R passes through the storage tank 40, the first enzyme reactor 10a, the second electrochemical reactor 20b, the second enzyme reactor 10b, and the first electrochemical reactor 20a in this order, for example. In this case, the first enzyme reactor 10a and the second electrochemical reactor 20b may form a first unit 5a, and the second enzyme reactor 10b and the first electrochemical reactor 20a may form a second unit 5b.

[0049] In the reaction device 1a, a voltage may be applied to the working electrode 25a and the counter electrode 25b in the first electrochemical reactor 20a and the second electrochemical reactor 20b by a single voltage application device 26. In this case, the working electrodes 25a in the first electrochemical reactor 20a and the second electrochemical reactor 20b may be connected in parallel to the voltage application device 26. Furthermore, the counter electrodes 25b in the first electrochemical reactor 20a and the second electrochemical reactor 20b may be connected in parallel to the voltage application device 26.

[0050] 4 is a diagram showing yet another example of a reaction apparatus according to an embodiment. As shown in Fig. 4, the reaction solution R may be supplied to the first enzyme reactor 10a or the second enzyme reactor 10b so as to pass through the first enzyme reactor 10a or the second enzyme reactor 10b in the direction of gravity, for example.

[0051] FIG. 5 is a diagram showing yet another example of a reaction apparatus according to an embodiment. As shown in FIG. 5, a temperature regulator 16 may be disposed around the first enzyme reactor 10a or the second enzyme reactor 10b. Enzymes generally tend to have high activity at temperatures between 30°C and 50°C and may be inactivated if exposed to an environment of 75°C or higher for a long period of time. Therefore, from the viewpoint of stabilizing the activity of the first enzyme 15a and the second enzyme 15b and promoting the enzymatic reaction, it is important to maintain the temperature around the first enzyme 15a and the second enzyme 15b within a predetermined range. Therefore, the temperature regulator 16 tends to stabilize the activity of the first enzyme 15a or the second enzyme 15b and promote the enzymatic reaction. The temperature regulator 16 includes, for example, a coiled heat transfer tube through which a heat medium such as water flows. The temperature regulator 16 may include a Peltier element.

[0052] The temperatures of the reaction solution R, the first enzyme 15a, and the second enzyme 15b may be adjusted by disposing a part of the reaction device 1a inside a thermostatic bath.

[0053] 6 is a diagram showing yet another example of a reaction apparatus according to an embodiment. As shown in FIG. 6, the reference electrode 25c may be omitted. When the distance between the working electrode 25a and the counter electrode 25b is short, for example, when the distance is within about 1 cm, the reference electrode 25c may be omitted.

[0054] FIG. 7 is a diagram showing yet another example of a reaction apparatus according to an embodiment. As shown in FIG. 7 , each of the first electrochemical reactor 20a and the second electrochemical reactor 20b may include multiple working electrodes 25a. In this case, for example, one counter electrode 25b may be disposed between a pair of working electrodes 25a. For example, if the first electrochemical reactor 20a or the second electrochemical reactor 20b includes three working electrodes 25a, the working electrodes 25a and counter electrodes 25b may be disposed in the following order: working electrode 25a, counter electrode 25b, working electrode 25a, counter electrode 25b, and working electrode 25a. For example, the multiple working electrodes 25a are connected in parallel to the voltage application device 26, and the multiple counter electrodes 25b are connected in parallel.

[0055] FIG. 8 is a diagram showing yet another example of a reaction apparatus according to an embodiment. As shown in FIG. 8 , the first chamber 21 of the first electrochemical reactor 20a or the second electrochemical reactor 20b may be directly connected to the first enzyme reactor 10a or the second enzyme reactor 10b. For example, the first chamber 21 may be separated from the interior of the first enzyme reactor 10a or the second enzyme reactor 10b by a first filter 11a or a second filter 11b. Even with this configuration, the first enzyme 15a remains inside the first enzyme reactor 10a, and the second enzyme 15b remains inside the second enzyme reactor 10b. Therefore, the first enzyme 15a and the second enzyme 15b are less susceptible to the influence of the first electrochemical reactor 20a and the second electrochemical reactor 20b, and deterioration of the first enzyme 15a and the second enzyme 15b can be suppressed.

[0056] The overall configuration of the reaction apparatus is described in Fig. 1, and the configurations relating to the first enzyme reactor 10a, the second enzyme reactor 10b, the first electrochemical reactor 20a, and the second electrochemical reactor 20b are described in Fig. 2. The configurations relating to the first enzyme reactor 10a and the second enzyme reactor 10b are described in Fig. 4 and Fig. 5, and the configurations relating to the first electrochemical reactor 20a and the second electrochemical reactor 20b are described in Fig. 6 to Fig. 8. The reaction apparatus may be configured by appropriately combining these configurations.

[0057] (Other Embodiments) The reaction apparatus and the method for producing a product have been described based on the embodiments. However, the present disclosure is not limited to these embodiments. As long as they do not deviate from the gist of the present disclosure, various modifications that a person skilled in the art can make to the embodiments and other embodiments formed by combining some of the components of the embodiments are included in the scope of the present disclosure.

[0058] (Additional Note) From the above description, the following techniques are disclosed.

[0059] (Technology 1) A catalytic reaction system comprising: a first enzyme reactor; a first electrochemical reactor; a second enzyme reactor; a second electrochemical reactor; a first enzyme disposed inside the first enzyme reactor; and a second enzyme disposed inside the second enzyme reactor, wherein the first enzyme reactor, the first electrochemical reactor, the second enzyme reactor, and the second electrochemical reactor are arranged so that a reaction solution passes through and circulates through the first electrochemical reactor, the first enzyme reactor, the second electrochemical reactor, and the second enzyme reactor in that order, wherein the reaction solution comprises a first substrate to be oxidized or reduced by the first enzyme, a second substrate to be oxidized or reduced by the second enzyme, and a coenzyme that restores the activity of the first enzyme after reacting with the first substrate and the activity of the second enzyme after reacting with the second substrate, wherein the first enzyme remains inside the first enzyme reactor when the reaction solution passes through the first enzyme reactor, and the second enzyme remains inside the second enzyme reactor when the reaction solution passes through the second enzyme reactor, The first electrochemical reactor and the second electrochemical reactor electrochemically restore the activity of the coenzyme.

[0060] (Technology 2) The reaction apparatus according to Technology 1, wherein the first enzyme reactor and the first electrochemical reactor form a first unit, and the second enzyme reactor and the second electrochemical reactor form a second unit.

[0061] (Technology 3) The reaction device according to Technology 1 or 2, wherein each of the first electrochemical reactor and the second electrochemical reactor comprises: a first chamber through which the reaction solution passes and in which a working electrode is disposed; a second chamber in which a counter electrode is disposed; a membrane separating the first chamber from the second chamber, preventing permeation of the coenzyme, the first substrate, and the second substrate, and having ion conductivity; and a voltage application device for applying a voltage between the working electrode and the counter electrode.

[0062] (Technology 4) The reaction device according to Technology 3, wherein the first chamber and the second chamber contain an electrolyte solution.

[0063] (Technology 5) The reaction apparatus according to Technology 3 or 4, wherein the membrane contains a polymer having a perfluoro side chain containing a sulfonic acid group.

[0064] (Technology 6) The reaction device according to any one of Technologies 1 to 5, wherein the first enzyme and the second enzyme are each supported on the surface of a carrier particle.

[0065] (Technology 7) The reaction device according to Technology 6, wherein the support particles comprise an organic polymer or a non-metallic inorganic material.

[0066] (Technology 8) The reaction apparatus according to Technology 6 or 7, wherein the carrier particles have an average particle size of 1 micrometer to 5 millimeters.

[0067] (Technology 9) The reaction apparatus according to any one of Technologies 1 to 8, wherein the first enzyme reactor further comprises a first filter that allows the coenzyme, the first substrate, and the second substrate to pass through and prevents the first enzyme from passing through when the reaction solution passes through the first enzyme reactor, and the second enzyme reactor further comprises a second filter that allows the coenzyme, the first substrate, and the second substrate to pass through and prevents the second enzyme from passing through when the reaction solution passes through the second enzyme reactor.

[0068] (Technology 10) The reaction apparatus according to Technology 9, wherein the first enzyme and the second enzyme are each supported on the surface of a carrier particle, and the first filter and the second filter have an average pore size smaller than half the average particle size of the carrier particle.

[0069] (Technology 11) A method for producing a product, comprising: passing a reaction solution containing a first substrate to be oxidized or reduced by a first enzyme, a second substrate to be oxidized or reduced by a second enzyme, and a coenzyme that restores the activity of the first enzyme after reacting with the first substrate and the activity of the second enzyme after reacting with the second substrate through a first electrochemical reactor, a first enzyme reactor, a second electrochemical reactor, and a second enzyme reactor in that order, thereby causing different enzymatic reactions in the first enzyme reactor and the second enzyme reactor, and electrochemically restoring the activity of the coenzyme in the first electrochemical reactor and the second electrochemical reactor; wherein the first enzyme remains inside the first enzyme reactor when the reaction solution passes through the first enzyme reactor, and the second enzyme remains inside the second enzyme reactor when the reaction solution passes through the second enzyme reactor.

[0070] (Technology 12) A catalytic converter comprising: a first enzyme reactor; a first electrochemical reactor; a second enzyme reactor; a second electrochemical reactor; a third enzyme reactor; a third electrochemical reactor; a first enzyme disposed inside the first enzyme reactor; a second enzyme disposed inside the second enzyme reactor; and a third enzyme disposed inside the third enzyme reactor, wherein the first enzyme reactor, the first electrochemical reactor, the second enzyme reactor, and the second electrochemical reactor are arranged so that a first reaction solution passes through and circulates in the order of the first electrochemical reactor, the first enzyme reactor, the second electrochemical reactor, and the second enzyme reactor, and wherein the second enzyme reactor, the second electrochemical reactor, the third enzyme reactor, and the third electrochemical reactor are arranged so that a second reaction solution passes through and circulates in the order of the second electrochemical reactor, the second enzyme reactor, the third electrochemical reactor, and the third enzyme reactor, the first reaction solution comprises a first substrate to be oxidized or reduced by the first enzyme, a second substrate to be oxidized or reduced by the second enzyme, and a first coenzyme that restores the activity of the first enzyme after reacting with the first substrate and the activity of the second enzyme after reacting with the second substrate; the second reaction solution comprises a second substrate to be oxidized or reduced by the second enzyme, a third substrate to be oxidized or reduced by the third enzyme, and a second coenzyme that restores the activity of the second enzyme after reacting with the second substrate and the activity of the third enzyme after reacting with the third substrate; the first enzyme remains inside the first enzyme reactor when the first reaction solution passes through the first enzyme reactor; the second enzyme remains inside the second enzyme reactor when the first reaction solution and the second reaction solution pass through the second enzyme reactor; the third enzyme remains inside the third enzyme reactor when the second reaction solution passes through the second enzyme reactor; The first electrochemical reactor, the second electrochemical reactor, and the third electrochemical reactor electrochemically restore the activity of the first coenzyme and the second coenzyme.

[0071] The reaction device of the present disclosure can be used, for example, as a reaction device for multiple types of enzyme reactions.

[0072] 1a Reactor 5a First unit 5b Second unit 10a First enzyme reactor 10b Second enzyme reactor 11a First filter 11b Second filter 15a First enzyme 15b Second enzyme 20a First electrochemical reactor 20b Second electrochemical reactor 21 First chamber 22 Second chamber 23 Membrane 25a Working electrode 25b Counter electrode 26 Voltage application device R Reaction solution

Claims

1. A reaction device comprising a first enzyme reactor, a first electrochemical reactor, a second enzyme reactor, a second electrochemical reactor, a first enzyme disposed inside the first enzyme reactor, and a second enzyme disposed inside the second enzyme reactor, wherein the first enzyme reactor, the first electrochemical reactor, the second enzyme reactor, and the second electrochemical reactor are arranged such that the reaction solution circulates through them in the order of the first electrochemical reactor, the first enzyme reactor, the second electrochemical reactor, and the second enzyme reactor, the reaction solution contains a first substrate oxidized or reduced by the first enzyme, a second substrate oxidized or reduced by the second enzyme, and a coenzyme for restoring the activity of the first enzyme after reacting with the first substrate and the activity of the second enzyme after reacting with the second substrate, the first enzyme remains inside the first enzyme reactor when the reaction solution passes through the first enzyme reactor, the second enzyme remains inside the second enzyme reactor when the reaction solution passes through the second enzyme reactor, and the first electrochemical reactor and the second electrochemical reactor electrochemically restore the activity of the coenzyme.

2. The reaction device according to claim 1, wherein the first enzyme reactor and the first electrochemical reactor form a first unit, and the second enzyme reactor and the second electrochemical reactor form a second unit.

3. Each of the first electrochemical reactor and the second electrochemical reactor comprises a first chamber through which the reaction solution passes and in which a working electrode is disposed, a second chamber in which a counter electrode is disposed, and a membrane that separates the first chamber and the second chamber, prevents the permeation of the coenzyme, the first substrate, and the second substrate, and has ion conductivity, and a voltage application device for applying a voltage between the working electrode and the counter electrode. The reaction device according to claim 1.

4. The reaction device according to claim 3, wherein an electrolyte solution is contained in the first chamber and the second chamber.

5. The reaction device according to claim 3, wherein the membrane contains a polymer having a perfluorinated side chain containing a sulfonic acid group.

6. The reaction device according to claim 1, wherein each of the first enzyme and the second enzyme is supported on the surface of carrier particles.

7. The reactor according to claim 6, wherein the carrier particles contain an organic polymer or a non-metallic inorganic material.

8. The reactor according to claim 6, wherein the carrier particles have an average particle size of from 1 micrometer to 5 millimeters.

9. The first enzyme reactor further comprises a first filter that allows the coenzyme, the first substrate, and the second substrate to permeate when the reaction solution passes through the first enzyme reactor and blocks the permeation of the first enzyme. The second enzyme reactor further comprises a second filter that allows the coenzyme, the first substrate, and the second substrate to permeate when the reaction solution passes through the second enzyme reactor and blocks the permeation of the second enzyme. The reactor according to claim 1.

10. Each of the first enzyme and the second enzyme is supported on the surface of the carrier particles. The first filter and the second filter have an average pore size smaller than half of the average particle size of the carrier particles. The reactor according to claim 9.

11. A method for producing a product, comprising passing a reaction solution containing a first substrate oxidized or reduced by a first enzyme, a second substrate oxidized or reduced by a second enzyme, and a coenzyme that restores the activity of the first enzyme after reacting with the first substrate and the activity of the second enzyme after reacting with the second substrate, in this order, through a first electrochemical reactor, a first enzyme reactor, a second electrochemical reactor, and a second enzyme reactor, causing different enzyme reactions in the first enzyme reactor and the second enzyme reactor, and electrochemically restoring the activity of the coenzyme in the first electrochemical reactor and the second electrochemical reactor, wherein the first enzyme remains inside the first enzyme reactor when the reaction solution passes through the first enzyme reactor, and the second enzyme remains inside the second enzyme reactor when the reaction solution passes through the second enzyme reactor.

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