JP4947368B2 - Information processing apparatus and method, and program - Google Patents

Description

  The present invention relates to an information processing apparatus and method, and a program, and in particular, can simulate a metabolic state from a starting material to an exhausted substance by an enzyme reaction and easily specify a more efficient enzyme network. The present invention relates to an information processing apparatus and method, and a program.

  In recent years, attention to environmental problems has increased, and the utilization of biotechnology has been studied in various technical fields as part of the solution. Along with this, research on biotechnology has been actively conducted.

  For example, there is a biofuel cell that uses, as a power source, energy obtained in the process of decomposing a high energy compound such as glucose into carbon dioxide using an enzyme. The production of metabolites using such enzyme reactions can be used in various fields such as medicine and chemistry.

  In the usual case, enzymes have reaction specificity and catalyze only certain chemical reactions. Therefore, in the production of metabolites by such an enzyme reaction, a plurality of enzymes are usually used in combination. In other words, the exhausted substance that is the target substance is generated from the starting material that is the material through a plurality of types of chemical reactions by a plurality of types of enzymes. This chemical reaction pathway is called a metabolic pathway. At present, thousands of kinds of enzymes are known, and each catalyzes a chemical reaction, so that a variety of metabolic pathway networks are constructed in the whole enzyme.

  When producing an effluent from a starting material, a necessary one is selected from those enzyme groups, and a metabolic pathway connecting the starting material and the effluent is constructed. The selection of the pathway, that is, the selected enzyme Changes the efficiency of the chemical reaction (metabolism). In other words, the productivity of emitted substances changes.

  In the natural world, combinations of enzymes and their distribution (enzyme network) are selected over a long period of time, and a number of metabolic pathways for producing effluents from predetermined starting materials have been developed. Some of them can be used for application purposes such as biofuel cells, but the performance required for living organisms and the performance required for fuel cells are fundamentally different. Not necessarily.

  Enzymes are collected from living organisms in nature. For example, there are enzymes that can be collected only from specific organisms, and combinations of enzymes that do not coexist in nature may be optimal for application purposes.

  Therefore, in order to increase the efficiency of the chemical reaction, it is necessary to select an enzyme from a group of known enzymes, and it is also necessary to examine various conditions for the chemical reaction. However, it is not practical to actually collect enzymes from nature, combine the enzymes while changing the conditions, and carry out exhaustive experiments for all the conditions, which is troublesome.

  Therefore, a method of simulating metabolism by such an enzyme reaction is conceivable (for example, see Non-Patent Document 1). In the case of simulation, since the reaction result of a chemical reaction can be calculated by calculation, a chemical reaction that requires time in an experiment can be obtained instantaneously, and various conditions can be covered easily and at high speed.

Yoichi Nakayama and Masaru Hamada, “E-CELL System and Dynamic / Static Hybrid Simulation Algorithm”, “Forefront of Metabolome Research”, Springer Fairlark Tokyo, November 30, 2003, P199-207

  However, with the conventional method, the specified metabolic pathway can be evaluated, but an efficient combination of enzymes is identified from thousands of known enzyme groups, and various more efficient conditions are identified. I couldn't. Therefore, in order to construct an efficient enzyme network, it is necessary to simulate various combinations of enzymes under various conditions in the dark clouds, and to compare the evaluation results, which requires complicated work. That is, the development cost and development time may increase.

  In addition, in order to reduce the amount of work, if the combination of enzymes to be simulated and the limitation of conditions are unnecessary, a combination of enzymes having more efficient metabolic pathways and more efficient chemical reaction conditions, that is, more There was a fear that an efficient enzyme network could not be obtained.

  The present invention has been proposed in view of such a conventional situation, and makes it possible to easily identify a more efficient enzyme network.

  A first aspect of the present invention is an information processing apparatus for simulating the state of metabolism from a starting material to an exhausted substance by an enzyme reaction, and sets the composition ratio of each enzyme of an enzyme group to be simulated And simulating the state of metabolism for the whole enzyme group by simulating the enzyme reaction by each enzyme whose composition ratio is set by the composition ratio setting means using the Michaelis-Menten equation. And controlling the emission amount calculation means for calculating the emission amount of the emission material after a predetermined time, the composition ratio setting means and the emission amount calculation means, and repeatedly calculating the emission amount while changing the composition ratio. A repetitive control means, a maximum value specifying means for specifying a maximum value among a plurality of discharge amounts calculated by the control of the repetitive control means, and the discharge amount calculation Means for removing an enzyme that has not been subjected to an enzyme reaction from the enzyme group when the maximum amount of discharge specified by the maximum value specifying means is calculated, The repetitive control unit controls the component ratio setting unit and the discharge amount calculating unit again for the enzyme group from which the unused enzyme is deleted by the unused enzyme deleting unit, and changes the component ratio while changing the component ratio. This is an information processing apparatus that repeatedly calculates the amount.

  The constituent ratio setting means can set the constituent ratio of a predetermined proportion of enzymes in the enzyme group to be simulated to zero.

  The apparatus further comprises an unnecessary enzyme deleting means for deleting an unnecessary enzyme that does not contribute to metabolism from the starting material to the excreted substance from the enzyme group to be simulated, and the component ratio setting means includes the unnecessary enzyme The constituent ratio of each enzyme in the enzyme group after the unnecessary enzyme is deleted by the deleting means can be set.

  Under the control of the repetition means, the calculation of the discharge amount is repeated a predetermined number of times while the unused enzyme is deleted by the unused enzyme deletion means, and then the maximum of the discharge amount specified by the maximum value specifying means. Display control means for causing the display unit to display the value and the enzyme group when the maximum value is calculated as image information can be further provided.

  Under the control of the repetition means, the calculation of the discharge amount is repeated a predetermined number of times while the unused enzyme is deleted by the unused enzyme deletion means, and then the maximum of the discharge amount specified by the maximum value specifying means. The storage control means for storing the value and the enzyme group when the maximum value is calculated in the storage unit can be further provided.

  The first aspect of the present invention is also an information processing method of an information processing apparatus for simulating the state of metabolism from a starting material to an exhausted substance by an enzyme reaction, and each of the enzyme groups to be simulated By setting the component ratio of the enzyme, and simulating the enzyme reaction by each enzyme with the component ratio set using the Michaelis-Menten equation, the state of metabolism is simulated for the entire enzyme group, Calculate the emission amount of the emitted substance after a predetermined time, calculate the emission amount repeatedly while changing the composition ratio, specify the maximum value from the repeatedly calculated emission amount, and release the specified maximum value The enzyme group in which the enzyme reaction has not been performed is deleted from the enzyme group in which is calculated, and further, the enzyme group from which the unused enzyme is deleted, while changing the component ratio An information processing method for repeatedly calculating the volume.

  In the first aspect of the present invention, the computer that simulates the metabolic state from the starting material to the discharged material by the enzyme reaction sets the composition ratio of each enzyme of the enzyme group to be simulated, By simulating the enzyme reaction by each enzyme with the composition ratio set using the Michaelis-Menten equation, the state of metabolism is simulated for the entire enzyme group, and the discharge of the discharge substance after a predetermined time Enzyme group when calculating the amount, repeatedly calculating the discharge amount while changing the composition ratio, specifying the maximum value from the repeatedly calculated discharge amount, and calculating the specified maximum discharge amount The enzyme that was not subjected to the enzyme reaction was deleted, and the discharge amount was calculated repeatedly while changing the composition ratio for the enzyme group from which the unused enzyme was deleted. Is a program that executes the processing that.

  In the first aspect of the present invention, the composition ratio of each enzyme of the enzyme group to be simulated is set, and the enzyme reaction by each enzyme for which the composition ratio is set is simulated using the Michaelis-Menten equation. As a result, the state of metabolism is simulated for the entire enzyme group, the amount of discharge after a predetermined time is calculated, the amount of discharge is calculated repeatedly while changing the composition ratio, and the amount of the calculated amount of discharge is calculated repeatedly. Enzymes that did not perform an enzyme reaction were deleted from the enzyme group when the maximum value was identified from among them, and the discharge amount of the specified maximum value was calculated. For the enzyme group, the discharge amount is repeatedly calculated while changing the composition ratio.

  According to the present invention, it is possible to simulate the state of metabolism from the starting material to the discharged material by the enzyme reaction. In particular, a more efficient enzyme network can be easily identified. Furthermore, the development cost and development time of biotechnology using enzymes can be reduced.

  Embodiments of the present invention will be described below. Correspondences between constituent elements of the present invention and the embodiments described in the specification or the drawings are exemplified as follows. This description is intended to confirm that the embodiments supporting the present invention are described in the specification or the drawings. Therefore, even if there is an embodiment which is described in the specification or the drawings but is not described here as an embodiment corresponding to the constituent elements of the present invention, that is not the case. It does not mean that the form does not correspond to the constituent requirements. Conversely, even if an embodiment is described here as corresponding to a configuration requirement, that means that the embodiment does not correspond to a configuration requirement other than the configuration requirement. It's not something to do.

  A first aspect of the present invention is an information processing apparatus (for example, the metabolic simulator 101 in FIG. 1) that simulates the state of metabolism from a starting material to an exhausted substance by an enzyme reaction, and is an object of simulation. The composition ratio setting means (for example, the enzyme allocation unit 163 in FIG. 3) for setting the composition ratio of each enzyme of the enzyme group, and the enzyme reaction by each enzyme whose composition ratio is set by the composition ratio setting means are Michaelis Menten By simulating using the equation, the metabolic state of the whole enzyme group is simulated, and the discharge amount calculating means for calculating the discharge amount of the discharged substance after a predetermined time (for example, the discharge amount calculation of FIG. 3) 164), the component ratio setting means and the discharge amount calculating means, and repeatedly calculating the discharge amount while changing the component ratio. (For example, the repetitive control unit 167 in FIG. 3) and maximum value specifying means for specifying the maximum value among a plurality of discharge amounts calculated by the control of the repetitive control unit (for example, the maximum value specifying unit 165 in FIG. 3). And an unused enzyme that deletes an enzyme that has not been subjected to an enzyme reaction from the enzyme group when the maximum amount specified by the maximum value specifying means is calculated by the discharge amount calculating means Delete unit (for example, unused route measure job 166 in FIG. 3), and the repetitive control unit sets the composition ratio again for the enzyme group from which the unused enzyme is deleted by the unused enzyme deletion unit. An information processing apparatus that controls the discharge amount calculation means and repeatedly calculates the discharge amount while changing the component ratio.

  The component ratio setting means can set the component ratio of an arbitrarily selected ratio of enzymes in the enzyme group to be simulated to zero (for example, step S22 in FIG. 5).

  An unnecessary enzyme deleting means (for example, an unnecessary path deleting unit 162 in FIG. 3) for deleting an unnecessary enzyme that does not contribute to metabolism from the starting material to the excreted material from the enzyme group to be simulated is further provided. The constituent ratio setting means can set the constituent ratio of each enzyme in the enzyme group after the unnecessary enzyme is deleted by the unnecessary enzyme deleting means.

  Under the control of the repetition means, the calculation of the discharge amount is repeated a predetermined number of times while the unused enzyme is deleted by the unused enzyme deletion means, and then the maximum of the discharge amount specified by the maximum value specifying means. The display control means (for example, the display control part 168 of FIG. 3) which displays a value and the enzyme group when the said maximum value is calculated on a display part as image information can be further provided.

  Under the control of the repetition means, the calculation of the discharge amount is repeated a predetermined number of times while the unused enzyme is deleted by the unused enzyme deletion means, and then the maximum of the discharge amount specified by the maximum value specifying means. The storage control unit (for example, the storage control unit 169 in FIG. 3) that stores the value and the enzyme group when the maximum value is calculated in the storage unit may be further provided.

  The first aspect of the present invention is also an information processing method of an information processing apparatus for simulating the state of metabolism from a starting material to an exhausted substance by an enzyme reaction, and each of the enzyme groups to be simulated The composition ratio of the enzyme is set (for example, step S6 in FIG. 4), and the enzyme reaction by each enzyme for which the composition ratio is set is simulated using the Michaelis-Menten equation. The state of metabolism is simulated, the emission amount of the emission substance after a predetermined time is calculated (for example, step S7 in FIG. 4), and the emission amount is repeatedly calculated while changing the composition ratio (for example, FIG. 4). Step S10), the maximum value is specified from the repeatedly calculated discharge amount (for example, Step S8 and Step S9 in FIG. 4), and the discharge amount of the specified maximum value is calculated. The enzyme that has not been subjected to the enzyme reaction is deleted from the enzyme group (eg, step S11 in FIG. 4), and the composition ratio is changed for the enzyme group from which the unused enzyme is deleted. However, the discharge amount is repeatedly calculated (for example, step S12 in FIG. 4).

  In the first aspect of the present invention, the computer that simulates the metabolic state from the starting material to the discharged material by the enzyme reaction sets the composition ratio of each enzyme of the enzyme group to be simulated ( For example, in step S6) of FIG. 4, the state of metabolism is simulated for the entire enzyme group by simulating an enzyme reaction by each enzyme with the composition ratio set using the Michaelis-Menten equation, The emission amount after a predetermined time of the emission material is calculated (for example, step S7 in FIG. 4), the emission amount is repeatedly calculated while changing the composition ratio (for example, step S10 in FIG. 4), and the calculation is repeated. The maximum value is specified from the discharge amount (for example, Step S8 and Step S9 in FIG. 4), and the enzyme group when the discharge amount of the specified maximum value is calculated Then, the enzyme that has not been subjected to the enzyme reaction is deleted (for example, step S11 in FIG. 4), and the discharge amount is repeatedly calculated while changing the composition ratio for the enzyme group from which the unused enzyme is deleted. (For example, step S12 in FIG. 4).

  Embodiments of the present invention will be described below.

  FIG. 1 is a diagram showing a configuration example of an information processing system to which the present invention is applied.

  In FIG. 1, an information processing system 100 has a metabolism simulator 101 and a database 102, and is a system that simulates the state of metabolism from a starting material to an exhausted material by an enzyme reaction.

  The metabolism simulator 101 is an information processing apparatus that performs processing related to a simulation of the state of metabolism from a starting material to an exhausted material by an enzyme reaction. The metabolism simulator 101 may be configured in any manner, and is configured by, for example, a personal computer. The database 102 stores information necessary for the simulation. The database 102 is configured by an arbitrary storage medium that can be read and written by the metabolic simulator 101, such as a hard disk, a semiconductor memory, an optical disk, a magneto-optical disk, or a magnetic disk. Note that the metabolic simulator 101 and the database 102 may be configured integrally, and the information processing system 100 may be configured as one device.

  FIG. 1 shows functional blocks representing functions that the metabolism simulator 101 mainly has. As shown in FIG. 1, the metabolic simulator 101 includes a simulation processing unit 111, an input unit 112, a display unit 113, a data reading unit 114, and a data writing unit 115 as main functional blocks.

  The simulation processing unit 111 has a function of performing processing related to a simulation of the state of metabolism from the starting material to the discharged material by an enzyme reaction. The simulation processing unit 111 includes, for example, a CPU (Central Processing Unit), a ROM (Read Only Memory), a RAM (Random Access Memory), and the like.

  The input unit 112 is configured by, for example, a keyboard, a mouse, and the like, and indicates a function of receiving information from the outside such as an operation instruction from the user. The input device constituting the input unit 112 is arbitrary, and may be, for example, a camera or a microphone or an external input terminal.

  The display unit 113 is configured by an arbitrary image display device such as an LCD or a CRT, and shows a function of displaying image information. The display unit 113 displays image information supplied from the simulation processing unit 111, such as a simulation GUI (Graphical User Interface) and a simulation result image.

  For example, when the simulation processing unit 111 starts a simulation, the data reading unit 114 has a function of reading information on an enzyme from the enzyme network database 121 of the database 102 and supplying the information to the simulation processing unit 111. The data reading unit 114 is configured by, for example, a driver of a storage medium that configures the database 102. The data reading unit 114 basically reads information about all the enzymes registered in the enzyme network database 121 and supplies the information to the simulation processing unit 111. For example, the enzyme requested by the simulation processing unit 111, etc. It is also possible to read out only information about a specific partial enzyme.

  The data writing unit 115 registers (stores) information related to the simulation result supplied from the simulation processing unit 111 in the creation data database 122 of the database 102. The data writing unit 115 is configured by, for example, a driver of a storage medium that configures the database 102.

As shown in FIG. 1, an enzyme network database 121 and a creation data database 122 are constructed in the database 102. The enzyme network database 121 is a database in which information on existing enzymes and enzyme reactions (metabolic pathways) catalyzed by each enzyme is registered. For example, it includes information such as the ID information of the enzyme, the reaction formula of the chemical reaction catalyzed by the enzyme, the Michaelis constant, the turnover number, and the specific activity. The Michaelis constant is a constant used in a reaction rate equation (Michaelis-Menten equation) representing a reaction rate of a chemical reaction. Michaelis constant K _m is the rate k _{+1 at} which enzyme E and substrate S become intermediate complex ES, the rate k ₋₁ at which intermediate complex ES becomes enzyme E and substrate S, and intermediate complex ES as products P and The following equation (1) can be expressed by using the speed k ₊₂ to become the enzyme E.

K _m = (k ₋₁ + k ₊₂ ) / k ₊₁ (1)

  If the substrate concentration is S, the Michaelis-Menten equation can be expressed as the following equation (2).

v = (V × [S]) / (K _m + [S]) (2)

  The turnover number indicates the number of substrates reacted per second per enzyme (number of turnover molecules per second per molecule of enzyme). Intrinsic activity is essentially the same as the number of turnovers, but in different units.

  The data reading unit 114 reads the information on the enzyme used for the simulation from the enzyme network database 121 and supplies it to the simulation processing unit 111.

  The creation data database 122 is a database in which simulation results and information related to the simulation results are registered. When the data writing unit 115 acquires various types of information indicating the simulation result supplied from the simulation processing unit 111, the data writing unit 115 supplies the information to the creation data database 122 and stores it.

  An outline of the operation will be described. Upon receiving a user instruction input via the input unit 112, the simulation processing unit 111 of the metabolic simulator 101 controls the data reading unit 114 to read the enzyme network information from the enzyme network database 121 of the database 102, Start the simulation. Then, when an efficient enzyme network is identified by simulation, the simulation processing unit 111 displays the simulation result on the display unit 113 as image information, and further controls the data writing unit 115 to store the simulation result in the database. 102 is stored in the creation data database 122.

  FIG. 2 is a diagram illustrating a display example when the enzyme network is displayed as image information by the display unit 113. As shown in FIG. 2, a window 131 which is a GUI for displaying an enzyme network is displayed on the monitor of the display unit 113, and an image of the enzyme network is drawn there. The enzyme network is represented by nodes that are points and edges that are lines connecting the nodes. Nodes represent substances such as enzymes, substrates, products, and edges represent their chemical reactions (ie metabolic pathways).

  In this window 131, for example, the entire enzyme network that is read from the enzyme network database 121 and is known in the information processing system 100 before the simulation is started is drawn. The user specifies the first starting material and the generated emission material from the drawn enzyme network, and starts the simulation. When the simulation is completed, an efficient enzyme network identified by the simulation is drawn in the window 131 as a simulation result.

  In this way, by displaying the enzyme network as image information (GUI), the user can more easily understand the state of the enzyme network, and more easily operate the metabolic simulator 101 and execute the simulation. it can.

  FIG. 3 is a functional block diagram illustrating detailed functions of the simulation processing unit 111 in FIG.

  In FIG. 3, the simulation processing unit 111 includes a calculation unit 151 that performs processing as a main configuration and a holding unit 152 that holds data. The calculation unit 151 includes a setting unit 161, an unnecessary route deletion unit 162, an enzyme allocation unit 163, a discharge amount calculation unit 164, a maximum value specification unit 165, an unused route deletion unit 166, a repetition control unit 167, a display control unit 168, and A storage control unit 169 is included.

  The setting unit 161 performs settings necessary for the simulation. For example, the setting unit 161 sets a group of enzymes to be simulated, a starting material and its amount, and a common substance such as a coenzyme that contributes to the catalytic action of the enzyme and its amount. Make the necessary settings. In addition, for example, setting of the execution environment such as setting of temperature and humidity, simulation time, and the like may be performed. The setting unit 161 can perform arbitrary settings.

  When the starting material and the discharged material are specified, the unnecessary route deleting unit 162 deletes a route that obviously does not contribute to the generation of the discharged material, such as a metabolic pathway, from the enzyme network that performs the simulation. For example, when the metabolic pathway is only for generating a substance other than the specified emission substance and the generated substance is not used for another chemical reaction, the path is deleted as an unnecessary path. By deleting unnecessary paths before starting the simulation in this way, the simulation processing unit 111 can reduce unnecessary computation, reduce the load caused by the simulation, and reduce the time required for the simulation. Can be made.

  The method for identifying this unnecessary path is arbitrary, but a simple example is a method of searching and deleting a node to which only one edge is connected from the entire enzyme network. However, in order to delete the unnecessary route more accurately, it is necessary to control not to delete the route more than necessary.

  The enzyme allocation unit 162 allocates an amount to each enzyme to be simulated based on a predetermined total amount. That is, the enzyme allocation unit 162 sets the composition ratio of each enzyme in the enzyme group to be simulated. The enzyme allocation unit 162 performs setting so that the composition ratio of each enzyme changes each time allocation is performed. This allocation method is arbitrary, and the allocation amount of each enzyme may be determined at random, or may be determined while changing the allocation amount of each enzyme according to a predetermined change pattern.

  The simulation is repeatedly executed while the allocation amount of each enzyme is changed each time by the enzyme allocation unit 162. Then, the discharge amount of the discharged substance at each time is compared, and the component ratio when the discharge amount reaches the maximum value is specified as the component ratio with the highest efficiency.

  In addition, the enzyme allocation part 162 makes the allocation amount of the enzyme of the predetermined ratio among each enzyme zero when performing allocation. For example, the enzyme allocation unit 162 sets the enzyme allocation amount to zero at a rate of one out of every five enzymes included in the enzyme group.

  As will be described later, the metabolic pathways are narrowed down by simulation. In general, there are many routes from the starting material to the discharged material, and they are related to each other in a complicated manner. For example, even in an enzyme reaction that produces only a small amount of product (inefficient metabolic pathway), the small amount of product produced greatly contributes to other enzyme reactions, greatly increasing the efficiency of emission generation. In some cases, it may be improved. In addition, for example, even in an enzyme reaction (an efficient metabolic pathway) that generates a large amount of product, the product generated in a large amount may contribute only slightly to the generation of effluent. As described above, in the metabolic pathway, the arrangement of the enzyme reactions is important, and the efficiency of each enzyme reaction itself hardly affects the entire pathway. Therefore, simply looking at the efficiency of a part of the metabolic pathway, it is difficult to determine whether or not the pathway is unnecessary, and it is difficult to narrow down.

  That is, in order to suppress unnecessary deletion of a route, the simulation processing unit 111 needs to delete only a metabolic route (an unused route) in which no enzyme reaction has been performed. However, if this is done, the pathway will not be deleted if an enzymatic reaction is performed even slightly, so there is a possibility that the narrowing of the metabolic pathway will not be performed.

  Therefore, the enzyme allocation unit 162 forcibly prevents the enzyme reaction of a predetermined ratio by setting the enzyme allocation amount to zero at a predetermined ratio. Naturally, the enzyme whose assigned amount is set to zero is subject to deletion, but as will be described later, the simulation processing unit 111 repeatedly performs the simulation while changing the assigned amount, so that the emission amount of the emission material is maximized. Occasionally only pathways that did not undergo enzymatic reactions are deleted. This is equivalent to tentatively deleting a route at a predetermined rate for the time being, and determining that only the route that has a small influence on the deletion (the route that maximizes the emission substance generation efficiency even if deleted) is determined. . By doing in this way, since the simulation process part 111 can pinpoint the path | route which does not contribute to the production | generation of an emitted substance more correctly, it can pinpoint a more efficient enzyme network easily.

  In addition, the ratio which makes an allocation amount zero is arbitrary. The ratio may be variable.

  The discharge amount calculation unit 164 performs a simulation of the enzyme reaction based on the set various conditions, and calculates the generation amount (discharge amount) of the discharge substance. The discharge calculation unit 164 simulates the metabolic state of the entire enzyme network by calculating each enzyme reaction using the Michaelis-Menten equation of each enzyme, and calculates the discharge after a predetermined time. . At this time, the discharge amount calculation unit 164 may perform the calculation in any procedure, but for example, by performing simulation in a short unit such as 1 minute or 1 second, and repeating the simulation, For example, a simulation for a predetermined time such as 60 minutes is performed.

  As described above, the maximum value specifying unit 165 specifies the maximum value from the discharge amount repeatedly calculated a predetermined number of times while changing the composition ratio of the enzyme. The unused route deletion unit 166 uses a route that has not been used in the simulation when the discharge amount reaches the maximum value, that is, a route (enzyme) in which the enzyme reaction has not been performed (the traffic was zero) as an enzyme. Remove from the network. The repetition control unit 167 controls the setting unit 161 to the unused route deletion unit 166 to repeatedly execute simulation.

  The display control unit 168 causes the display unit 113 to display the maximum value of the finally specified emission amount, the enzyme network that discharges the emission material having the maximum value, and the like as simulation results. The storage control unit 169 stores the maximum value of the finally specified discharge amount, the enzyme network that discharges the discharge material having the maximum value, and the like in the creation data database 122 as a simulation result.

  The holding unit 152 includes various information such as an enzyme network 181, starting material information 182, discharged material information 183, common material information 184, enzyme amount allocation information 185, reaction information 186, maximum discharge amount 187, and maximum enzyme network 188. Information is retained.

  The enzyme network 181 is information related to the enzyme network to be simulated, read from the enzyme network database 121. The starting material information 182 is information on the starting material including information on the starting material set by the setting unit 161 and its amount. The emission material information 183 is information related to the emission material set by the setting unit 161. The common substance information 184 is information related to the common substance including information on the common substance set by the setting unit 161 and the amount thereof. The enzyme amount allocation information 185 is information on the allocated amount of each enzyme allocated by the enzyme allocation unit 163. The reaction information 186 is information related to the enzyme reaction of each enzyme calculated by the discharge amount calculation unit 164. The discharge amount calculation unit 164 performs a simulation of the entire network while holding the intermediate result of the calculation as reaction information 186 in the holding unit 152. The maximum discharge amount value 187 is information indicating the maximum discharge amount calculated by the discharge amount calculation unit 164. The maximum-time enzyme network 188 is information on the enzyme network when the discharge amount reaches the maximum value.

  Next, an example of the flow of simulation processing executed by each unit of the simulation processing unit 111 will be described with reference to the flowchart of FIG.

  For example, when the simulation process is started based on a user instruction received via the input unit 112, the setting unit 161 controls the data reading unit 114 in step S1, and the simulation is performed from the enzyme network database 121. Read out the enzyme network. In step S <b> 2, the setting unit 161 sets a starting material in the simulation based on, for example, a user instruction received via the input unit 112. At this time, the setting unit 161 also sets the amount (concentration) of the starting material. For example, the setting unit 161 sets glucose as a starting material and 40000 nmol as its concentration.

Next, in step S <b> 3, the setting unit 161 sets emission substances in the simulation based on, for example, a user instruction received via the input unit 112. For example, the setting unit 161 sets carbon dioxide (CO ₂ ) as the emission material.

In step S4, the unnecessary route deleting unit 162 deletes the unnecessary route. In step S <b> 5, the setting unit 161 sets a common substance in the simulation based on, for example, a user instruction received via the input unit 112. At this time, the setting unit 161 also sets the amount (concentration) of the common substance. For example, the setting unit 161 includes, as common substances, NAD + (reduced NADH) that is an oxidized form of nicotinamide adenine dinucleotide, NADP + (reduced NADPH) that is an oxidized form of nicotinamide adenine dinucleotide phosphate, and nicotinamide adenine. Dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin adenine dinucleotide phosphate (FADP), adenosine triphosphate (ATP), glutamyltransferase (GTP), uridine dilin Acid (UDP), oxygen (O ₂ ), water (H ₂ O), inorganic phosphate (Orthophosphate), guanosine diphosphate (GDP), adenosine diphosphate (ADP), hydrogen ion (H +), hydrogen (Hydrogen) ), And Coenzyme A (CoA), the total concentration is 400000 nmol, that is, 10 times the starting material Set. In addition, if the amount of the common substance is within the range of common sense, even if it is too much, the generation efficiency of the discharged substance is not affected.

  In step S6, the enzyme allocation unit 163 sets the allocation amount of each enzyme to be simulated. Details of the allocation amount setting process will be described later.

When the setting of the allocated amount is completed, the emission amount calculation unit 164 simulates the enzyme reaction and calculates the emission amount of the emission substance (CO ₂ ) for 60 minutes in step S7. Details of the discharge amount calculation processing will be described later.

  In step S8, the maximum value specifying unit 165 determines whether or not the discharge amount calculated this time in the process of step S7 is larger than the maximum discharge amount value 187 held in the holding unit 152, and determines that it is large. In step S9, the discharge amount maximum value 187 held in the holding unit 152 is updated with the discharge amount calculated this time. That is, the discharge amount calculated this time is held in the holding unit 152 as a new discharge amount maximum value 187. When the process of step S9 ends, the process proceeds to step S10. When it is determined in step S9 that the currently calculated emission amount is equal to or less than the emission amount maximum value 187, the maximum value specifying unit 165 omits the process of step S9 and updates the emission amount maximum value 187. Without the process, the process proceeds to step S10.

  In step S10, the repetition control unit 167 determines whether or not the simulation has been repeated a predetermined number of times. If it is determined that the simulation has not been repeated, the process returns to step S1 and controls to repeat the subsequent processes. That is, the simulation processing unit 111 repeats the processing from step S1 to step S10 a predetermined number of times. At this time, the enzyme allocation unit 163 sets the allocation amount so as to change the composition ratio of each enzyme every time.

  If it is determined in step S10 that the calculation of the discharge amount has been repeated a predetermined number of times, the process proceeds to step S11. In step S11, the unused route deletion unit 166 deletes, from the enzyme network, a route in which traffic is zero in the enzyme network when the discharge amount reaches the maximum value, that is, an enzyme in which the enzyme reaction has not been performed.

  In step S12, the repetition control unit 167 further determines whether or not the simulation has been repeated a predetermined number of times. If it is determined that the simulation has not been repeated, the process returns to step S1 and controls to repeat the subsequent processes. That is, the simulation processing unit 111 repeats the processing from step S1 to step S12 a predetermined number of times.

  In the simulation, emissions are calculated for various conditions. Therefore, the emission amount may increase by chance due to a phenomenon that occurs very rarely only under special conditions. Such a unique case may have low reproducibility. Therefore, in order to obtain an enzyme network that can more reliably expect a high discharge amount, the iterative control unit 167 performs control so as to obtain a discharge value maximum value a plurality of times.

  If it is determined in step S12 that the process has been repeated a predetermined number of times, the repeat control unit 167 advances the process to step S13. In step S <b> 13, the display control unit 168 causes the display unit 113 to display the calculated maximum discharge amount value 187 and the numerical value of the enzyme concentration of each enzyme at that time. Further, in step S14, the display control unit 168 draws the metabolic pathway (maximum enzyme network 188) when the discharge amount is maximum as shown in FIG. 2 by using nodes and edges, and displays the image information. Displayed on the unit 113.

  In step S <b> 15, the storage control unit 169 registers the calculated maximum discharge amount and information on the enzyme concentration of each enzyme at that time in the creation database 122. When the process of step S15 ends, the simulation process ends.

  Next, an example of a detailed flow of the allocation amount setting process executed in step S6 of FIG. 4 will be described with reference to the flowchart of FIG.

  When the allocation amount setting process is started, the enzyme allocation unit 163 identifies an enzyme to which an enzyme amount (concentration) is allocated based on the enzyme network 181 held as a simulation target in the holding unit 152 in step S21. To do. That is, the enzyme assignment unit 163 sets the enzymes included in the enzyme network 181 as assignment targets.

  In step S22, the enzyme assigning unit 163 sets an enzyme whose assigned amount is zero at a predetermined ratio. As described above, the enzyme assignment unit 163 sets the concentration of some of the assignment target enzymes to 0 nmol.

  In step S23, the enzyme allocation unit 163 determines the allocation amount (concentration) of each remaining enzyme based on the preset total amount of enzyme. That is, the enzyme assignment unit 163 sets the composition ratio of each enzyme.

  When the process of step S23 ends, the enzyme assigning unit 163 returns the process to step S6 of FIG. 4 to execute the processes after step S7.

  Next, an example of a detailed flow of the emission amount calculation process executed in step S7 of FIG. 4 will be described with reference to the flowchart of FIG.

  When the discharge amount calculation process is started, the discharge amount calculation unit 164 selects a new target enzyme for simulating an enzyme reaction from unprocessed enzymes in the enzyme network 181 in step S41. When an enzyme is selected, the discharge amount calculation unit 164 uses a Michaelis-Menten equation or the like in step S42 to indicate a reaction concentration (that is, an amount of reaction) per minute of an enzyme reaction catalyzed by the enzyme (that is, an enzyme concentration). Is equivalent to the reaction rate), and in step S43, the concentration of the substrate, which is a substance to be chemically reacted, is calculated after 1 minute (substrate concentration after 1 minute), and in step S44, the calculated substrate concentration and Based on the reaction concentration, the concentration after 1 minute (product concentration after 1 minute) of the product that is a material generated from the substrate by the chemical reaction is calculated.

  In step S45, the iterative control unit 167 determines whether or not the reaction concentration, the substrate concentration, and the product concentration have been calculated for all the enzymes, and there is an unprocessed enzyme in the enzyme network 181 to be processed. If it is determined, the process returns to step S41, and the subsequent processes are controlled to be repeated.

  In Step S45, when it is determined that the respective concentrations have been calculated for all the enzymes, that is, the simulation for one minute has been completed, the repetition control unit 167 advances the processing to Step S46. In step S46, the discharge amount calculation unit 164 adds the discharge amount of the discharge substance calculated by obtaining the respective concentrations for all the enzymes to the total discharge amount held.

  In step S47, the repetitive control unit 167 performs a simulation for 60 minutes, determines whether or not the discharge amount after 60 minutes has been calculated, and determines that the discharge amount after 60 minutes has not yet been calculated. Then, the process is returned to step S41, and the subsequent processes are controlled to be repeated. If it is determined in step S47 that the discharge amount after 60 minutes has been calculated, the repeat control unit 167 ends the discharge amount calculation processing, returns the processing to step S7 in FIG. 4, and performs the processing after step S8. Let it run.

  In the above description, it has been described that the discharge amount calculation unit 164 calculates the discharge amount after 60 minutes by performing one-minute simulations 60 times, but the time and method of simulation are arbitrary. For example, a simulation every 10 minutes may be performed 6 times, a simulation in units of seconds may be repeated, a discharge amount after 120 minutes may be calculated, or 24 hours The subsequent discharge amount may be calculated. Of course, you may make it apply time other than these.

  As described above, the calculation of the emission amount is repeated while changing the composition ratio of the enzyme, the path where the enzyme reaction has not been performed in the enzyme network where the emission amount is maximum is deleted (淘汰), and the emission amount is calculated. By repeating the above, the information processing system 100 can specify a more efficient enzyme network. Thereby, the user can easily specify a more efficient enzyme network.

  In addition, since the enzyme allocation unit 163 can activate the deletion (淘汰) of the pathway by setting the composition ratio of a predetermined ratio of enzymes arbitrarily selected at the time of allocation to zero, information processing The system 100 can identify a more efficient enzyme network.

  Moreover, the unnecessary route deletion unit 162 deletes a route unnecessary for generating the emission material in advance, thereby reducing the load of simulation processing and the simulation time.

  Furthermore, the display control unit 168 causes the display unit 113 to display the simulation result, so that the user can easily grasp the simulation result.

  Further, the storage control unit 169 stores the simulation result in the created data database 122, so that the user can check the simulation result at an arbitrary timing after the simulation. Further, the simulation result can be used for other processes at an arbitrary timing.

  Below, the example of the enzyme network calculated | required by the above simulations is demonstrated.

FIG. 7 is a diagram illustrating an example of an enzyme network identified by the information processing system 100 of FIG. The enzyme network 200 shown in FIG. 7 forms a metabolic network having glucose as a starting material and CO ₂ as an effluent, and efficiently generates and discharges CO ₂ from glucose. In addition, electrons are emitted in the process of metabolism. That is, the enzyme network 200 is suitable for use as an enzyme network for biofuel cells because it efficiently generates electrons from glucose.

  First, the outline of the configuration of the enzyme network 200 of FIG. 7 will be described. In FIG. 7, the metabolic pathway of the enzyme network 200 is indicated by arrows (edges). Nodes connected by the edges and indicated by squares in the figure indicate substrates, enzymes, and the like. That is, in FIG. 7, the enzyme network 200 is shown as a series of enzyme reactions by each enzyme. Specifically, one enzyme reaction is basically represented by the following formula (3), and the enzyme network 200 has a configuration in which a plurality of formulas (3) are linked to each other.

  S → (E + S) → (E + P) → P (3)

  In the formula (3), S represents a substrate, E represents an enzyme, and P represents a product. That is, each process of one enzyme reaction is shown by three edges (four nodes). However, in FIG. 7, the substrate and the product include common substances such as coenzymes. Further, as shown in FIG. 7, the direction of the arrow (edge) may be reversed. In FIG. 7, for example, nodes indicated by white squares such as the node 211 and the node 214 indicate the S and P terms in the expression (3). For example, gray squares such as the node 212 and the node 213 are used. The nodes shown indicate the terms (E + S) and (E + P) in equation (3). That is, as shown in FIG. 7, the enzyme network 200 is a combination of enzyme reactions having a common substrate and product.

  The simulation results of the enzyme network 200 of FIG. 7 are shown in FIGS. The configuration of the enzyme network 200 will be described more specifically with reference to these.

  The list described in the range 301 of FIG. 8 is a list of enzyme reactions performed in the enzyme network 200, and each row indicates a portion of (E + S) → (E + P) in the equation (3). . For example, “2.7.1.2 [ATP, D-Glucose] → 2.7.1.2 [ADP, D-Glucose 60 phosphate]” in the second line from the top indicates a chemical reaction from the node 212 to the node 213 in FIG. . These details are described in FIGS. 9 to 16, and will be described later with reference to them.

  A final product (exhaust substance) and its concentration (exhaust amount) are shown in a range 302 in FIG.

  9 to 16 show details of the enzyme reaction. Since the configurations of the ranges 311 to 336 in FIGS. 9 to 16 are basically the same, first, the configuration will be described with reference to the range 311 of FIG.

  The ID of the enzyme is shown in “ID” on the first line from the top. This ID is identification information for identifying each enzyme, and is a so-called EC number. The EC number is an ID assigned by the Enzyme Committee of the International Biochemical Union, and consists of a combination of four numbers. Enzymes are classified according to differences in reaction specificity and substrate specificity. The EC number indicates where the enzyme belongs in this category. Of the four numbers, they are subdivided from left to right. The enzyme is further given a system name in which the name of the substrate molecule and the name of the reaction are linked. For some enzymes, common names that are shortened by omitting part of the substrate may be used.

  In the present embodiment, an enzyme is identified using an EC number. However, as long as each enzyme can be identified in the enzyme network database 121, any identification information may be used to identify the enzyme.

  The “Reaction” in the second line from the top shows the enzyme reaction formula. This is the same as the list described in the range 301 of FIG. 8, and shows the part of (E + S) → (E + P) in the equation (3). The description of each range from the range 311 to the range 336 describes information in units of reaction. Since some enzymes may react in the opposite direction, there may be two reactions for one enzyme. In that case, each reaction is described using two ranges.

  “Michaelis Constant” on the third line from the top indicates the Michaelis constant of this enzymatic reaction. The Michaelis constant of each enzyme reaction is registered in advance in the enzyme network database 121. In the present embodiment, Brenda from Cologne University in Germany is used as the enzyme network database 121. That is, the value defined in Brenda is used as the value of the Michaelis constant.

  “Turnover Number” on the fourth line from the top indicates the turnover number of this enzyme reaction. This turnover number is also defined in the enzyme network database 121 as in the Michaelis constant. In the present embodiment, the value defined in Brenda is used.

  “Specific Activity” on the fifth line from the top indicates the specific activity of this enzyme reaction. Similar to the turnover number and Michaelis constant, this unique activity is also defined in the enzyme network database 121. In this embodiment, the value defined in Brenda is used.

  “Organism” on the 6th line from the top is a list of organism names where the enzyme exists in nature. “Amount” in the second line from the bottom indicates the allocated amount (concentration) of the enzyme. 9 to 16 show the assigned amount (concentration) of each enzyme when the emission amount of the emission substance takes the maximum value. “Traffic” in the first line from the bottom indicates the reaction concentration of the enzyme reaction. This reaction rate is a value calculated by the discharge amount calculation unit 164 based on the Michaelis constant, the turnover number, the substrate concentration, the allocated amount of the enzyme, and the like.

  The configuration of FIG. 7 will be described with reference to a range 311 to a range 336 in which information is described with the above configuration.

  In FIG. 7, a node 211 is “D-Glucose” which is a starting material and is a substrate of an enzyme reaction from the node 212 to the node 213. The starting material concentration is “40000.0 nmol”.

  Information about the enzymatic reaction from node 212 to node 213 is described in range 311 of FIG. That is, the node 212 indicates the enzyme (glucokinase) with ID “2.7.1.2” and “D-Glucose” and “ATP” which are substrates of this enzyme reaction, and the node 213 indicates the ID “2.7.1.2”. An enzyme (glucokinase) and “ADP” and “D-Glucose 6-phosphate” which are products of this enzyme reaction are shown. The Michaelis constant of this enzymatic reaction is “0.028 mmol / l”, the turnover number is “410.0 / s”, and the specific activity is “370.0 umol / min / mg”. This enzyme (2.7.1.2) can be collected from, for example, E. coli, bacteria, rats, and humans. Further, the allocated amount (concentration) of the enzyme (2.7.1.2) is “6.344967267689803 nmol”. The traffic of this enzymatic reaction was “40000.0 nmol”.

  The node 214 indicates “D-Glucose 6-phosphate” which is a product of the enzyme reaction from the node 212 to the node 213. The node 214 (D-Glucose 6-phosphate) is also a substrate for the enzyme reaction from the node 215 to the node 216 and a product of the enzyme reaction from the node 216 to the node 215.

  Information about the enzyme reaction from node 215 to node 216 is described in range 330 of FIG. That is, the node 215 indicates the enzyme (glucose-6-phosphate dehydrogenase) with ID “1.1.1.49”, and “NADP +” and “D-Glucose 6-phosphate”, which are substrates of this enzyme reaction, , ID “1.1.1.49” enzyme (glucose-6-phosphate dehydrogenase) and the products of this enzyme reaction “NADPH”, “h”, “D-Glucono-1”, and “5-lactone 6” -phosphate ". The Michaelis constant of this enzymatic reaction is “1.2000000000000002E-5 mmol / l”, the turnover number is “30100.0 / s”, and the specific activity is “790.0 umol / min / mg”. . This enzyme (1.1.1.49) can be collected from, for example, green pea, corn, wild boar, candida, bacteria, rats, dogs, cows, and humans. Further, the allocated amount (concentration) of this enzyme (1.1.1.49) is “5.723009684711666 nmol”. The traffic of this enzymatic reaction was “40000.0 nmol”.

  Information about the enzyme reaction from node 216 to node 215 is described in range 331 of FIG. The Michaelis constant of this enzymatic reaction is “0.014 mmol / l” and the turnover number is “10.0 / s”. The traffic of this enzyme reaction was “0.0 nmol”.

  Node 217 indicates “D-Glucono-1” and “5-lactone 6-phosphate”, which are products of the enzyme reaction from node 215 to node 216. The node 217 (D-Glucono-1 and 5-lactone 6-phosphate) is also a substrate for the enzyme reaction from the node 216 to the node 215 and a substrate for the enzyme reaction from the node 218 to the node 219.

Information about the enzyme reaction from node 218 to node 219 is described in range 326 of FIG. That is, the node 218 includes an enzyme with ID “3.1.1.31” (6-phosphogluconolactonase), and “H ₂ 0”, “D-Glucono-1”, and “5-lactone 6-” that are substrates for this enzymatic reaction. Node ”219 indicates an enzyme with ID“ 3.1.1.31 ”(6-phosphogluconolactonase) and“ 6-Phospho-D-gluconate ”which is a product of this enzyme reaction. The Michaelis constant of this enzymatic reaction is “0.08 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “6753.0 umol / min / mg”. This enzyme (3.1.1.31) can be collected from, for example, rats, humans, cows, and E. coli. Moreover, the allocated amount (concentration) of this enzyme (3.1.1.31) is “7.107184800310227 nmol”. The traffic of this enzymatic reaction was “40000.0 nmol”.

  Node 220 indicates “6-Phospho-D-gluconate”, which is a product of the enzyme reaction from node 218 to node 219. This node 220 (6-Phospho-D-gluconate) is also a substrate for the enzyme reaction from the node 221 to the node 222.

Information about the enzyme reaction from node 221 to node 222 is described in range 336 of FIG. That is, the node 221 indicates the enzyme of ID “4.2.1.12” (phosphogluconate dehydratase) and “6-Phospho-D-gluconate” which is a substrate of this enzyme reaction, and the node 222 has the ID “4.2.1.12”. As well as “H ₂ 0” and “2-Dehydro-3-deoxy-6-phospho-D-gluconate”, which are the products of this enzymatic reaction. The Michaelis constant of this enzymatic reaction is “0.04 mmol / l”, and the turnover number is “100.0 / s”. This enzyme (4.2.1.12) can be collected from, for example, rhizobia, Escherichia coli, and Candida fungi. Further, the allocated amount (concentration) of the enzyme (4.2.1.12) is “3.3411991914852237 nmol”. The traffic of this enzymatic reaction was “40000.0 nmol”.

  A node 223 indicates “2-Dehydro-3-deoxy-6-phospho-D-gluconate”, which is a product of the enzyme reaction from the node 221 to the node 222. Note that this node 223 (2-Dehydro-3-deoxy-6-phospho-D-gluconate) is also a substrate for the enzyme reaction from the node 224 to the node 225 and a substrate for the enzyme reaction from the node 225 to the node 224. is there.

  Information about the enzyme reaction from node 224 to node 225 is described in range 334 of FIG. That is, the node 224 includes an enzyme with ID “4.1.2.14” (2-dehydro-3-deoxy-phosphogluconate aldolase) and “2-Dehydro-3-deoxy-6-phospho-D” which is a substrate of the enzyme reaction. -gluconate ", and node 225 shows an enzyme with ID" 4.1.2.14 "(2-dehydro-3-deoxy-phosphogluconate aldolase) and" Pyruvate "and" (2R)- 2-Hydroxy-3- (phosphonooxy) -propanal ". The Michaelis constant of this enzymatic reaction is “0.0060 mmol / l”, the turnover number is “533.0 / s”, and the specific activity is “625.0 umol / min / mg”. This enzyme (4.1.2.14) can be collected from, for example, rhizobia or Escherichia coli. Further, the allocated amount (concentration) of this enzyme (4.1.2.14) is “1.459436730959706 nmol”. The traffic of this enzymatic reaction was “40000.0 nmol”.

  Information about the enzyme reaction from node 225 to node 224 is described in range 335 of FIG. The Michaelis constant of this enzymatic reaction is “10.0 mmol / l” and the turnover number is “6.0 / s”. The traffic of this enzyme reaction was “0.0 nmol”.

  Node 226 indicates “(2R) -2-Hydroxy-3- (phosphonooxy) -propanal”, which is the product of the enzymatic reaction from node 224 to node 225. The node 226 ((2R) -2-Hydroxy-3- (phosphonooxy) -propana) is a substrate for the enzyme reaction from the node 225 to the node 224, a substrate for the enzyme reaction from the node 228 to the node 229, and It is also the product of the enzymatic reaction from node 229 to node 228.

Information about the enzyme reaction from node 228 to node 229 is described in range 316 of FIG. That is, the node 228 includes an enzyme (glyceraldehyde-3-phosphate dehydrogenase) having an ID “1.2.1.9”, and “(2R) -2-Hydroxy-3- (phosphonooxy) -propanal”, which is a substrate of the enzyme reaction, “NADP +” and “H ₂ O” are shown, and a node 229 is an enzyme (glyceraldehyde-3-phosphate dehydrogenase) having an ID “1.2.1.9” and “3-Phospho-D” which is a product of this enzyme reaction. -glycerate "," NADPH ", and two" h ". The Michaelis constant of this enzyme reaction is “0.017 mmol / l”, the turnover number is “103.0 / s”, and the specific activity is “150.5 umol / min / mg”. This enzyme (1.2.1.9) can be collected from, for example, green peas, bacteria, corn, wheat, and spinach. The amount (concentration) of this enzyme (1.2.1.9) is “6.260318661362094 nmol”. The traffic of the enzyme reaction was “47510.533612162806 nmol”.

  Information about the enzyme reaction from node 229 to node 228 is described in range 317 of FIG. The Michaelis constant of this enzymatic reaction is “0.062 mmol / l” and the turnover number is “10.0 / s”. The traffic of this enzyme reaction was “7510.533612162805 nmol”.

  The node 230 indicates “3-Phospho-D-glycerate”, which is a product of the enzyme reaction from the node 228 to the node 229. This node 230 (3-Phospho-D-glycerate) is a substrate for enzyme reaction from node 229 to node 228, a product of enzyme reaction from node 237 to node 238, and an enzyme reaction from node 238 to node 237. , The substrate of the enzyme reaction from node 239 to node 240, and the product of the enzyme reaction from node 240 to node 239.

  Node 227 indicates “Pyruvate” which is the product of the enzyme reaction from node 224 to node 225. This node 226 (Pyruvate) is a substrate of the enzyme reaction from the node 225 to the node 224, a substrate of the enzyme reaction from the node 231 to the node 232, a product of the enzyme reaction from the node 232 to the node 231, and the node 262 The product of the enzyme reaction from node 263, the substrate of the enzyme reaction from node 263 to node 262, and the substrate of the enzyme reaction from node 264 to node 265.

  Information about the enzyme reaction from node 231 to node 232 is described in range 328 of FIG. That is, the node 231 indicates an enzyme (pyruvate kinase) with an ID “2.7.1.40” and “ATP” and “Pyruvate” which are substrates of the enzyme reaction, and a node 232 indicates an enzyme with an ID “2.7.1.40”. (Pyruvate kinase) and "ADP" and "Phosphoenolpyruvate" which are products of this enzymatic reaction. The Michaelis constant of this enzymatic reaction is “0.48 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “1685.0 umol / min / mg”. This enzyme (2.7.1.40) can be collected from, for example, wild boar, bacteria, Salmonella, spinach, cows, rabbits, dogs, Euglena, humans, rats, and E. coli. Further, the allocated amount (concentration) of this enzyme (2.7.1.40) is “5.644579048497802 nmol”. The traffic of this enzyme reaction was “93983.78606942232 nmol”.

  Information about the enzyme reaction from the node 232 to the node 231 is described in a range 329 in FIG. The Michaelis constant of this enzymatic reaction is “0.03 mmol / l”, and the turnover number is “232.0 / s”. The traffic of this enzyme reaction was “60916.44483227227 nmol”.

  The node 233 indicates “Phosphoenolpyruvate” that is a product of the enzyme reaction from the node 231 to the node 232. The node 233 (Phosphoenolpyruvate) is also a substrate for the enzyme reaction from the node 232 to the node 231, a substrate for the enzyme reaction from the node 234 to the node 235, and a product of the enzyme reaction from the node 235 to the node 234. .

Information about the enzyme reaction from node 234 to node 235 is described in range 313 of FIG. That is, the node 234 indicates the enzyme with ID “4.2.1.11” (phosphopyruvate hydratase) and “Phosphoenolpyruvate” and “H ₂ O” which are substrates of this enzyme reaction, and the node 235 has ID “4.2.1.11”. The enzyme (phosphopyruvate hydratase) and “2-Phospho-D-glycerate” which is a product of this enzyme reaction are shown. The Michaelis constant of this enzymatic reaction is “0.11 mmol / l”, and the turnover number is “10.0 / s”. This enzyme (4.2.1.11) can be collected from, for example, corn, wild boar, candida, rabbit, bacteria, rat, dog, cow, E. coli, and human. Further, the allocated amount (concentration) of this enzyme (4.2.1.11) is “5.677655768238286 nmol”. The traffic of this enzyme reaction was “39875.078162698206 nmol”.

  Information about the enzyme reaction from node 235 to node 234 is described in range 312 of FIG. The Michaelis constant of this enzymatic reaction is “0.0 mmol / l”, the turnover number is “230.0 / s”, and the intrinsic activity is “1118.0 umol / min / mg”. The traffic of the enzyme reaction was “6807.736925548192 nmol”.

  Node 236 indicates “2-Phospho-D-glycerate”, which is a product of the enzyme reaction from node 234 to node 235. The node 233 (2-Phospho-D-glycerate) is a substrate for the enzyme reaction from the node 235 to the node 234, a substrate for the enzyme reaction from the node 237 to the node 238, and an enzyme from the node 238 to the node 237. It is also the product of the reaction.

  Information about the enzyme reaction from node 237 to node 238 is described in range 332 of FIG. That is, the node 237 indicates an enzyme (phosphoglycerate mutase) with an ID “5.4.2.1” and “2-Phospho-D-glycerate” which is a substrate for this enzyme reaction, and the node 238 has an ID “5.4.2.1”. As well as “3-Phospho-D-glycerate” which is a product of this enzyme reaction. The product “3-Phospho-D-glycerate” is shown in the node 230 described above. Further, the Michaelis constant of this enzyme reaction is “0.041 mmol / l”, the turnover number is “199.0 / s”, and the specific activity is “2880.0 umol / min / mg”. This enzyme (5.4.2.1) can be collected from, for example, corn, wheat, wild boar, nematodes, rabbits, bacteria, rats, cows, Escherichia coli, rice, humans and Candida fungi. Further, the allocated amount (concentration) of the enzyme (5.4.2.1) is “5.5627079024453545 nmol”. The traffic of the enzyme reaction was “63015.941943861675 nmol”.

  Information about the enzyme reaction from node 238 to node 237 is described in range 333 of FIG. Note that “3-Phospho-D-glycerate”, which is a substrate for this enzyme reaction, is shown in the node 230 described above. The Michaelis constant of this enzymatic reaction is “0.026 mmol / l” and the turnover number is “530.0 / s”. The traffic of this enzyme reaction was “29948.60070671166 nmol”.

Information about the enzyme reaction from node 239 to node 240 is described in range 325 of FIG. Note that the substrate of this enzyme reaction is shown in the node 230 described above. That is, the node 239 indicates the enzyme with ID “3.1.3.38” (3-phosphoglycerate phosphatase), and “3-Phospho-D-glycerate” and “H ₂ O” which are substrates of this enzyme reaction, and the node 240 Indicates the enzyme with ID “3.1.3.38” (3-phosphoglycerate phosphatase) and “D-Glycerate” and “Orthophosphate” which are products of this enzyme reaction. Further, the Michaelis constant of this enzyme reaction is “0.28 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “740.0 umol / min / mg”. This enzyme (3.1.3.38) can be collected from, for example, green pea, corn, alfalfa, and spinach. Moreover, the allocated amount (concentration) of this enzyme (3.1.3.38) is “2.938928995971154 nmol”. The traffic of the enzyme reaction was “73067.34123715002 nmol”.

  The node 241 indicates “Orthophosphate” which is a product of the enzyme reaction from the node 239 to the node 240. A node 242 indicates “D-Glycerate” which is a product of an enzyme reaction from the node 239 to the node 240. The node 242 (D-Glycerate) is also a substrate for the enzyme reaction from the node 243 to the node 244 and a product of the enzyme reaction from the node 244 to the node 243.

  Information about the enzyme reaction from node 243 to node 244 is described in range 318 of FIG. In other words, the node 243 indicates the enzyme (hydroxypyruvate reductase) with ID “1.1.1.81”, and “D-Glycerate” and “NADP +” which are substrates of this enzyme reaction, and the node 244 has the ID “1.1.1.81”. The enzyme (hydroxypyruvate reductase) and “Hydroxypyruvate”, “NADPH” and “h” which are products of this enzyme reaction are shown. The Michaelis constant of this enzyme reaction is “0.037 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “943.0 umol / min / mg”. This enzyme (1.1.1.81) can be collected from, for example, green pea, corn, rat, wild boar, cow, and spinach. Further, the allocated amount (concentration) of this enzyme (1.1.1.81) is “20.00797589129738 nmol”. The traffic of this enzyme reaction was “354833.7646339715 nmol”.

  Information about the enzyme reaction from node 244 to node 243 is described in range 319 of FIG. The Michaelis constant of this enzymatic reaction is “0.015 mmol / l”, and the turnover number is “10.0 / s”. The traffic of this enzyme reaction was “281766.4233968215 nmol”.

  Node 245 indicates “Hydroxypyruvate” which is the product of the enzymatic reaction from node 243 to node 244. The node 245 (Hydroxypyruvate) is also a substrate for the enzyme reaction from the node 244 to the node 243 and a substrate for the enzyme reaction from the node 246 to the node 247.

Information about the enzyme reaction from node 246 to node 247 is described in range 327 of FIG. That is, the node 246 indicates the enzyme (hydroxypyruvate decarboxylase) with ID “4.1.1.40” and “Hydroxypyruvate” which is a substrate of this enzyme reaction, and the node 247 indicates the enzyme (hydroxypyruvate decarboxylase) with ID “4.1.1.40”. And “Glycolaldehyde” and “CO ₂ ” which are products of this enzymatic reaction. The Michaelis constant of this enzymatic reaction is “1.0 mmol / l”, and the turnover number is “100.0 / s”. This enzyme (4.1.1.40) can be collected from, for example, dogs, cows, rabbits, rats, and boars. Further, the allocated amount (concentration) of the enzyme (4.1.1.40) is “4.032799046786325 nmol”. The traffic of the enzyme reaction was “73067.34123715002 nmol”.

  Node 248 indicates “Glycolaldehyde” which is the product of the enzymatic reaction from node 246 to node 247. This node 248 (Glycolaldehyde) is also a substrate for the enzyme reaction from the node 249 to the node 251 and a substrate for the enzyme reaction from the node 251 to the node 249.

  Further, the node 250 indicates “NAD +” which is a substrate of the enzyme reaction from the node 249 to the node 251 and a product of the enzyme reaction from the node 251 to the node 249.

Information about the enzyme reaction from node 249 to node 251 is described in range 314 of FIG. That is, the node 249 indicates the enzyme (glycolaldehyde dehydrogenase) with ID “1.2.1.21”, and “Glycolaldehyde”, “NAD +”, and “H ₂ O” that are substrates of this enzyme reaction, and the node 251 indicates the ID. “1.2.1.21” enzyme (glycolaldehyde dehydrogenase), and “Glycolate”, “NADH”, and two “h”, which are products of this enzyme reaction, are shown. The Michaelis constant of this enzymatic reaction is “0.027 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “30.5 umol / min / mg”. This enzyme (1.2.1.21) can be collected from bacteria, Salmonella, Escherichia coli, and the like. Further, the allocated amount (concentration) of this enzyme (1.2.1.21) is “7.061585889861108 nmol”. The traffic of the enzyme reaction was “105296.45600275489 nmol”.

  Information about the enzyme reaction from node 251 to node 249 is described in range 315 of FIG. The Michaelis constant of this enzymatic reaction is “5.9000000000000025E-8 mmol / l”, and the turnover number is “10.0 / s”. The traffic of the enzyme reaction was “32229.114765604863 nmol”.

  The node 252 indicates a product of the enzyme reaction from the node 249 to the node 251 and “NADH” which is a substrate of the enzyme reaction from the node 251 to the node 249.

  A node 253 indicates a product of the enzyme reaction from the node 249 to the node 251 and “Glycolate” which is a substrate of the enzyme reaction from the node 251 to the node 249. This node 253 (Glycolate) is also a substrate for the enzyme reaction from the node 254 to the node 256.

  Information about the enzyme reaction from node 254 to node 256 is described in range 320 of FIG. That is, the node 254 indicates the enzyme (glycolate dehydrogenase) with ID “1.1.99.14” and the substrates “Glycolate” and “Acceptor” of this enzyme reaction, and the node 256 indicates the enzyme with ID “1.1.99.14”. (Glycolate dehydrogenase) and “Glyoxylate” and “Reduced acceptor” which are products of this enzymatic reaction. The Michaelis constant of this enzymatic reaction is “0.04 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “3.1 umol / min / mg”. This enzyme (1.1.99.14) can be collected from, for example, Donariella algae, Euglena, and Arabidopsis. Moreover, the allocated amount (concentration) of this enzyme (1.1.99.14) is “6.219569206751489 nmol”. The traffic of the enzyme reaction was “73067.34123715002 nmol”.

  The node 255 indicates “Acceptor” which is a substrate of the enzyme reaction from the node 254 to the node 256.

  The node 257 indicates “Reduced acceptor” that is a product of the enzyme reaction from the node 254 to the node 256.

  Node 258 shows “Glyoxylate” which is the product of the enzymatic reaction from node 254 to node 256. This node 258 (Glyoxylate) is also a substrate for the enzyme reaction from the node 259 to the node 260.

Information about the enzyme reaction from the node 259 to the node 260 is described in a range 321 in FIG. That is, the node 259 indicates the enzyme (malate synthase) with the ID “2.3.3.9” and the substrates of the enzyme reaction “Acetyl-CoA”, “H ₂ O”, and “Glyoxylate”, and the node 260 indicates , ID (2.3.3.9) enzyme (malate synthase), and products of this enzyme reaction, “(S) -Malate” and “CoA”. The Michaelis constant of this enzymatic reaction is “5.9E-4 mmol / l”, the turnover number is “161.0 / s”, and the specific activity is “25090.0 umol / min / mg”. This enzyme (2.3.3.9) can be collected from, for example, Donariella algae, Euglena, and Arabidopsis thaliana. Further, the allocated amount (concentration) of the enzyme (2.3.3.9) is “6.1659687812423245 nmol”. The traffic of the enzyme reaction was “73067.34123715002 nmol”.

  The node 261 indicates “(S) -Malate” which is a product of the enzyme reaction from the node 259 to the node 260. This node 261 ((S) -Malate) is also a substrate for the enzyme reaction from the node 262 to the node 263 and a product of the enzyme reaction from the node 263 to the node 262.

Information about the enzyme reaction from node 262 to node 263 is described in range 322 of FIG. That is, the node 262 indicates the enzyme (malate dehydrogenase) with the ID “1.1.1.40”, and “(S) -Malate” and “NADP +” which are substrates of the enzyme reaction, and the node 263 indicates the ID “1.1. 1.40 "enzyme (malate dehydrogenase) and" Pyruvate "," CO ₂ ", and" NADPH "which are the products of this enzymatic reaction. The product “Pyruvate” is shown in the node 227 described above. The Michaelis constant of this enzymatic reaction is “0.00118 mmol / l”, the turnover number is “582.0 / s”, and the intrinsic activity is “7910.0 umol / min / mg”. This enzyme (1.1.1.40) can be collected from, for example, corn, wild boar, rabbit, rhizobia, human, wheat, rat, and cow. Further, the allocated amount (concentration) of this enzyme (1.1.1.40) is “5.307051508393477 nmol”. The traffic of the enzyme reaction was “73067.34123715002 nmol”.

  Information about the enzyme reaction from node 263 to node 262 is described in range 323 of FIG. The Michaelis constant of this enzymatic reaction is “0.0020 mmol / l”, and the turnover number is “10.0 / s”. The traffic of this enzyme reaction was “0.0 nmol”.

Information about the enzyme reaction from node 264 to node 265 is described in range 324 of FIG. That is, the node 264 indicates an enzyme with ID “1.2.1.51” (pyruvate dehydrogenase) and “Pyruvate”, “CoA”, and “NADP +”, which are substrates for this enzymatic reaction, and node 265 has an ID “1.2”. .1.51 "(pyruvate dehydrogenase) and the products of this enzymatic reaction," Acetyl-CoA "," CO ₂ ", and" NADPH ". This substrate “Pyruvate” is shown in the node 227 described above. The Michaelis constant of this enzymatic reaction is “0.0066 mmol / l”, the turnover number is “100.0 / s”, and the intrinsic activity is “15.3 umol / min / mg”. This enzyme (1.2.1.51) can be collected from, for example, Euglena. Further, the allocated amount (concentration) of the enzyme (1.2.1.51) is “1.145061623996569 nmol”. The traffic of the enzyme reaction was “80000.0 nmol”.

  Node 266 indicates “Acetyl-CoA” which is the product of the enzyme reaction from node 264 to node 265. This node 266 (Acetyl-CoA) is also a substrate for the enzyme reaction from the node 259 to the node 260.

A simulation result having the above configuration is shown in a range 337 in FIG. When the starting material was “D-Glucose” and the emission material was “CO ₂ ” and the emission amount after 60 minutes was calculated, the maximum value of the emission amount was “226134.6824743001 nmol”.

  The efficiency of this enzyme network 200 is compared with the pentose phosphate cycle, which is a known metabolic pathway.

  FIG. 17 is a diagram illustrating a configuration example of a pentose phosphate circuit. In FIG. 17, the notation method of the pentose phosphate circuit 400 is basically the same as that of the enzyme network 200 of FIG.

  The simulation results of the pentose phosphate circuit 400 of FIG. 17 are shown in FIGS. The configuration of the pentose phosphate circuit 400 will be described more specifically with reference to these.

  The list described in the range 501 of FIG. 18 is a list of enzyme reactions performed in the pentose phosphate circuit 400. Since the described format is the same as that in FIG.

  A range 502 in FIG. 18 shows the final product (exhaust substance) and its concentration (exhaust amount).

  19 to 23 show details of the enzyme reaction. The configurations of ranges 511 to 527 in FIGS. 19 to 23 are basically the same as those in FIGS. 9 to 16.

  The configuration of FIG. 17 will be described with reference to ranges 511 to 527 in which information is described in the configuration as described above.

  In FIG. 17, a node 411 indicates “D-Glucose” which is a starting material and is a substrate for an enzyme reaction from the node 413 to the node 414. The starting material concentration is “40000.0 nmol”.

  A node 412 indicates “ATP” which is a substrate of an enzyme reaction from the node 413 to the node 414.

  Information about the enzyme reaction from node 413 to node 414 is described in range 513 in FIG. The node 413 indicates the enzyme (glucokinase) with the ID “2.7.1.2” and the substrates “D-Glucose” and “ATP” of the enzyme reaction, and the node 414 indicates the ID “2.7.1.2” (glucokinase). And "ADP" and "D-Glucose 6-phosphate" which are products of this enzyme reaction. The traffic of this enzymatic reaction was “40000.0 nmol”.

  Node 415 indicates “ADP”, which is a product of the enzyme reaction from node 413 to node 414.

  A node 416 indicates “D-Glucose 6-phosphate” which is a product of an enzyme reaction from the node 413 to the node 414. This node (D-Glucose 6-phosphate) is a substrate for enzyme reaction from node 417 to node 418, a product of enzyme reaction from node 418 to node 417, and a generation of enzyme reaction from node 445 to node 446. As well as the substrate of the enzymatic reaction from node 446 to node 445.

  Information about the enzyme reaction from the node 417 to the node 418 is described in a range 521 in FIG. Node 417 indicates an enzyme (glucose-6-phosphate dehydrogenase) with ID “1.1.1.49” and substrates for this enzyme reaction, “NADP +” and “D-Glucose 6-phosphate”. “1.1.1.49” enzyme (glucose-6-phosphate dehydrogenase) and the products of this enzyme reaction “NADPH”, “h”, “D-Glucono-1”, and “5-lactone 6-phosphate” Is shown. Moreover, the allocated amount (concentration) of this enzyme (1.1.1.49) is “0.974925718932978 nmol”. The traffic of this enzyme reaction was “107162.98046962103 nmol”.

  Information about the enzyme reaction from node 418 to node 417 is described in range 522 of FIG. The traffic of this enzyme reaction was “10524.11222672474 nmol”.

  Node 419 indicates “h”, which is the product of the enzymatic reaction from node 417 to node 418. This node 419 (h) is also a substrate for the enzyme reaction from the node 418 to the node 417.

  Node 420 represents “D-Glucono-1” and “5-lactone 6-phosphate”, which are products of the enzyme reaction from node 417 to node 418. This node 420 (D-Glucono-1 and 5-lactone 6-phosphate) is also a substrate for the enzyme reaction from the node 422 to the node 423.

The node 421 indicates “H ₂ O” which is a substrate of the enzyme reaction from the node 422 to the node 423.

Information about the enzyme reaction from node 422 to node 423 is described in range 516 of FIG. The node 422 includes an enzyme with ID “3.1.1.31” (6-phosphogluconolactonase) and “H ₂ 0”, “D-Glucono-1”, and “5-lactone 6-phosphate” which are substrates for this enzymatic reaction. The node 423 indicates an enzyme (ID 6.3.1.31) (6-phosphogluconolactonase) and “6-Phospho-D-gluconate” which is a product of the enzyme reaction. Further, the allocated amount (concentration) of the enzyme (3.1.1.31) is “7.7214390937079305 nmol”. The traffic of this enzyme reaction was “96638.8682428963 nmol”.

  The node 424 indicates “6-Phospho-D-gluconate”, which is a product of the enzyme reaction from the node 422 to the node 423. Note that the node 424 (6-Phospho-D-gluconate) is also a substrate of the enzyme reaction from the node 425 to the node 426 and a product of the enzyme reaction from the node 426 to the node 425.

Information about the enzyme reaction from node 425 to node 426 is described in range 514 of FIG. The node 425 indicates an enzyme (phosphogluconate dehydrogenase) having an ID “1.1.1.44” and “6-Phospho-D-gluconate” and “NADP +” which are substrates of the enzyme reaction, and the node 426 has an ID “1.1. 1.44 "of an enzyme (phosphogluconate dehydrogenase), as well as a product of the enzymatic reaction" D-Ribulose "," 5-phosphate "indicates" CO ₂ ", and" NADPH ". The Michaelis constant of this enzyme reaction is “0.0060 mmol / l”, the turnover number is “98.0 / s”, and the specific activity is “175.0 umol / min / mg”. This enzyme (1.1.1.44) can be collected from, for example, green pea, rat, wild boar, bacteria, silkworm, Salmonella, human, spinach, Candida, rice, and Escherichia coli. Further, the allocated amount (concentration) of this enzyme (1.1.1.44) is “1.032908096565134 nmol”. The traffic of this enzyme reaction was “96638.8682428963 nmol”.

  Information about the enzyme reaction from node 426 to node 425 is described in range 515 of FIG. The Michaelis constant of this enzymatic reaction is “2.2E-4 mmol / l”, and the turnover number is “10.0 / s”. The traffic of this enzyme reaction was “0.0 nmol”.

Node 427 indicates “CO ₂ ” which is the product of the enzyme reaction from node 425 to node 426. This node 427 (CO ₂ ) is also a substrate for the enzyme reaction from the node 426 to the node 425.

  Node 428 indicates “D-Ribulose 5-phosphate” which is a product of the enzyme reaction from node 425 to node 426. In addition, this node 428 (D-Ribulose 5-phosphate) is a substrate of the enzyme reaction from the node 429 to the node 430, a substrate from the node 432 to the node 433, and a product of the enzyme reaction from the node 433 to the node 432. But there is.

  Information about the enzyme reaction from node 429 to node 430 is described in range 527 of FIG. The node 429 indicates an enzyme (ribulose-phosphate 3-epimerase) with an ID “5.1.3.1” and “D-Ribulose 5-phosphate” which is a substrate for this enzyme reaction, and the node 430 has an ID “5.1.3.1”. And the enzyme "ribulose-phosphate 3-epimerase" and "D-Xylulose 5-phosphate" which is a product of this enzyme reaction. The Michaelis constant of this enzyme reaction is “0.19 mmol / l”, the turnover number is “7100.0 / s”, and the specific activity is “11610.0 umol / min / mg”. This enzyme (5.1.3.1) can be collected from, for example, rice, bacteria, rats, spinach, cattle, Escherichia coli, rabbits, rice, and humans. Moreover, the allocated amount (concentration) of this enzyme (5.1.3.1) is “62.774954936062876 nmol”. The traffic of this enzyme reaction was “68319.43412144815 nmol”.

  The node 431 indicates “D-Xylulose 5-phosphate” that is a product of the enzyme reaction from the node 429 to the node 430. This node 431 (D-Xylulose 5-phosphate) is a substrate for the enzyme reaction from the node 435 to the node 436, a product of the enzyme reaction from the node 436 to the node 435, and an enzyme reaction from the node 439 to the node 441. It is also the substrate and the product of the enzymatic reaction from node 441 to node 439.

  Information about the enzyme reaction from the node 432 to the node 433 is described in a range 511 in FIG. The node 432 indicates the enzyme (ribose-5-phosphate isomerase) with ID “5.3.1.6” and “D-Ribulose 5-phosphate” which is a substrate for this enzyme reaction, and the node 433 has the ID “5.3.1.6”. "Enzyme" (ribose-5-phosphate isomerase) and "D-Ribulose 5-phosphate" which is a product of this enzyme reaction. The Michaelis constant of this enzymatic reaction is “0.108 mmol / l”, the turnover number is “3440.0 / s”, and the specific activity is “1700.0 umol / min / mg”. This enzyme (5.3.1.6) can be collected from, for example, green pea, rat, wild boar, cow, Escherichia coli, human, Candida, spinach and the like. Further, the allocated amount (concentration) of the enzyme (5.3.1.6) is “13.091980787699258 nmol”. The traffic of this enzyme reaction was “22503.965709252243 nmol”.

  Information about the enzymatic reaction from node 433 to node 432 is described in range 512 of FIG. The Michaelis constant of this enzymatic reaction is “0.66 mmol / l” and the turnover number is “50.0 / s”. The traffic of the enzyme reaction was “50823.399830700386 nmol”.

  Node 434 indicates “D-Ribulose 5-phosphate”, which is a product of the enzyme reaction from node 432 to node 433. This node 434 (D-Ribulose 5-phosphate) is a substrate for enzyme reaction from node 433 to node 432, a substrate for enzyme reaction from node 435 to node 436, and an enzyme reaction from node 436 to node 435. It is also the product of

  Information about the enzyme reaction from node 435 to node 436 is described in range 525 of FIG. The node 435 indicates an enzyme (transketolase) having an ID “2.2.1.1” and “D-Ribose 5-phosphate” and “D-Xylulose 5-phosphate” which are substrates of the enzyme reaction. “2.2.1.1” enzyme (transketolase) and “Sedoheptulose 7-phosphate” and “(2R) -2-Hydroxy-3- (phosphonooxy) -propanal” which are products of this enzyme reaction are shown. The Michaelis constant of this enzyme reaction is “4.0 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “50.4 umol / min / mg”. This enzyme (2.2.1.1) can be collected from, for example, rat, wheat, wild boar, E. coli, rabbit, human, Candida, spinach and the like. Further, the allocated amount (concentration) of this enzyme (2.2.1.1) is “6.4130119777843735 nmol”. The traffic of this enzyme reaction was “16896.943255219718 nmol”.

  Information about the enzyme reaction from node 436 to node 435 is described in range 526 of FIG. The Michaelis constant of this enzymatic reaction is “0.0056 mmol / l” and the turnover number is “56.7 / s”. The traffic of this enzyme reaction was “45216.37737666786 nmol”.

  Node 437 indicates “(2R) -2-Hydroxy-3- (phosphonooxy) -propanal”, which is a product of the enzyme reaction from node 435 to node 436. This node 437 ((2R) -2-Hydroxy-3- (phosphonooxy) -propanal) is a substrate of the enzyme reaction from the node 436 to the node 435 and a product of the enzyme reaction from the node 439 to the node 441. , The product of the enzyme reaction from node 439 to node 441, the substrate of the enzyme reaction from node 441 to node 439, the substrate of the enzyme reaction from node 443 to node 444, and the enzyme reaction from node 444 to node 443 It is also a product.

  Node 438 indicates “Sedoheptulose 7-phosphate”, which is a product of the enzyme reaction from node 435 to node 436. Note that this node 438 (Sedoheptulose 7-phosphate) is also a substrate of the enzyme reaction from the node 443 to the node 444 and a product of the enzyme reaction from the node 444 to the node 443.

  Information about the enzyme reaction from the node 439 to the node 441 is described in a range 523 in FIG. Node 439 shows the enzyme (transketolase) with ID “2.2.1.1” and “D-Erythrose 4-phosphate” and “D-Xylulose 5-phosphate” which are substrates for this enzymatic reaction. “2.2.1.1” enzyme (transketolase) and “(2R) -2-Hydroxy-3- (phosphonooxy) -propanal” and “D-Fructose 6-phosphate” which are products of this enzyme reaction are shown. The Michaelis constant of this enzyme reaction is “0.0056 mmol / l”, the turnover number is “69.0 / s”, and the specific activity is “50.4 umol / min / mg”. Further, the allocated amount (concentration) of this enzyme (2.2.1.1) is “6.4130119777843735 nmol”. The traffic of this enzyme reaction was “93511.79261905616 nmol”.

  Information about the enzyme reaction from node 441 to node 439 is described in range 524 of FIG. The Michaelis constant of this enzymatic reaction is “4.9 mmol / l” and the turnover number is “10.0 / s”. The traffic of this enzyme reaction was “65192.35849760802 nmol”.

  Node 440 indicates “D-Erythrose 4-phosphate”, which is a substrate for the enzyme reaction from node 439 to node 441. The node 440 (D-Erythrose 4-phosphate) is a product of an enzyme reaction from the node 441 to the node 439, a product of an enzyme reaction from the node 443 to the node 444, and a node 443 to a node 443. It is also a substrate for enzyme reactions.

  Node 442 indicates “D-Fructose 6-phosphate”, which is a product of the enzyme reaction from node 439 to node 441. This node 442 (D-Fructose 6-phosphate) is a substrate for the enzyme reaction from the node 441 to the node 439, a product of the enzyme reaction from the node 443 to the node 444, and an enzyme reaction from the node 444 to the node 443. It is also the substrate, the substrate of the enzyme reaction from node 445 to node 446, and the product of the enzyme reaction from node 446 to node 445.

  Information about the enzyme reaction from node 443 to node 444 is described in range 517 of FIG. The node 443 includes an enzyme (transaldolase) with ID “2.2.1.2”, and “Sedoheptulose 7-phosphate” and “(2R) -2-Hydroxy-3- (phosphonooxy) -propanal”, which are substrates of the enzyme reaction. Node 444 indicates an enzyme (transaldolase) with ID “2.2.1.2” and “D-Erythrose 4-phosphate” and “D-Fructose 6-phosphate” which are products of this enzyme reaction. The Michaelis constant of this enzymatic reaction is “0.038 mmol / l”, the turnover number is “100.0 / s”, and the specific activity is “60.0 umol / min / mg”. This enzyme (2.2.1.2) can be collected from, for example, Euglena, Rats, cattle, E. coli, rabbits, humans, Candida and spinach. Further, the allocated amount (concentration) of this enzyme (2.2.1.2) is “0.9861131028717981 nmol”. The traffic of this enzyme reaction was “38921.48722484376 nmol”.

  Information about the enzyme reaction from node 444 to node 443 is described in range 518 of FIG. The Michaelis constant of this enzymatic reaction is “0.2 mmol / l”, and the turnover number is “10.0 / s”. The traffic of this enzyme reaction was “10602.053103395614 nmol”.

  Information about the enzyme reaction from node 445 to node 446 is described in range 519 of FIG. A node 445 indicates an enzyme (glucose-6-phosphate isomerase) having an ID “5.3.1.9” and “D-Glucose 6-phosphate” which is a substrate of the enzyme reaction, and a node 446 has an ID “5.3.1.9”. "Enzyme" (glucose-6-phosphate isomerase) and "D-Fructose 6-phosphate" which is a product of this enzyme reaction. Further, the Michaelis constant of this enzyme reaction is “0.03 mmol / l”, the turnover number is “42.0 / s”, and the specific activity is “1470.0 umol / min / mg”. This enzyme (5.3.1.9) can be collected from, for example, green pea, wild boar, rabbit, dog, human, spinach, wheat, bacteria, rat, cow, and Escherichia coli. Further, the allocated amount (concentration) of this enzyme (5.3.1.9) is “4.943054351198328 nmol”. The traffic of this enzyme reaction was “49675.42881604301 nmol”.

  Information about the enzyme reaction from node 446 to node 445 is described in range 520 of FIG. In addition, the Michaelis constant of this enzyme reaction is “0.01 mmol / l”, and the turnover number is “3330.0 / s”. The traffic of this enzyme reaction was “106314.2970589393 nmol”.

A result of simulating the pentose phosphate circuit 400 having the above configuration is shown in a range 528 of FIG. When the starting material was “D-Glucose” and the emission material was “CO ₂ ” and the emission amount after 60 minutes was calculated, the maximum value of the emission amount was “96638.8682428963 nmol”.

As shown in the range 337 of FIG. 16, in the case of the enzyme network 200, the maximum value of the emission amount is “226134.6824743001 nmol”, and thus the enzyme network 200 is more efficient in CO ₂ than the pentose phosphate circuit 400. Generate and discharge. That is, the enzyme network 200 can emit electrons more efficiently than the pentose phosphate circuit 400 which is a known metabolic circuit.

  FIG. 24 is a cross-sectional view showing a main configuration example of a biofuel cell using the enzyme network 200 as described above.

The biofuel cell 600 is a cell that uses as an electromotive force electrons generated when glucose is metabolized to carbon dioxide (CO ₂ ) by an enzyme. As shown in FIG. 24, the inside of the housing 611 of the biofuel cell 600 is hollow, and is provided with an anode 621 and a cathode 623. Further, glucose and the enzyme network 200 are placed on the anode side 612 of the hollow. When inserted, the enzyme reaction as described above occurs on the anode side 612, electrons are released, and electrons accumulate in the anode 621. Further, when hydrogen ions (H +) and oxygen molecules (O ₂ ) are chemically reacted on the cathode side 613 to generate water (H ₂ O) and electrons are consumed on the cathode side 613, the anode 621 and A potential difference occurs with the cathode 623. Therefore, when the anode 621 and the cathode 613 are connected to each other via the resistor 622 outside the housing 611, a potential difference occurs between both ends of the resistor 622, and current flows.

  Such a biofuel cell 600 has conventionally used an enzyme network existing in nature, such as the pentose phosphate circuit 400, but the enzyme network 200 as shown in FIG. By using it, the power generation efficiency can be improved.

  As described above, the information processing system 100 in FIG. 1 can easily identify a more efficient enzyme network by simulating the state of metabolism from the starting material to the discharged material by the enzyme reaction. This can also reduce the development cost and development time of biotechnology using enzymes.

  Although only the enzyme network used for the biofuel cell has been described above, the purpose of using the enzyme network is arbitrary. That is, the information processing system 100 simply identifies an enzyme network that efficiently generates an emission material from a starting material, so that an enzyme network with good metabolic efficiency can be used in any technical field. Can be requested. For example, the information processing system 100 can obtain an enzyme network used for a biofuel cell using a substance other than glucose as a fuel, or can obtain an enzyme network used for producing a drug or the like.

  The series of processes described above can be executed by hardware or can be executed by software. In this case, for example, a personal computer as shown in FIG. 25 may be configured.

  25, the CPU 711 of the personal computer 700 executes various processes according to a program stored in the ROM 712 or a program loaded from the storage unit 723 to the RAM 713. The RAM 713 also stores data necessary for the CPU 711 to execute various processes as appropriate.

  The CPU 711, the ROM 712, and the RAM 713 are connected to each other via a bus 714. An input / output interface 720 is also connected to the bus 714.

  The input / output interface 720 includes an input unit 721 including a keyboard and a mouse, a display including a CRT and an LCD, an output unit 722 including a speaker, a storage unit 723 including a hard disk, a modem, and the like. A communication unit 724 is connected. The communication unit 724 performs communication processing via a network including the Internet.

  A drive 725 is connected to the input / output interface 720 as necessary, and a removable medium 731 such as a magnetic disk, an optical disk, a magneto-optical disk, or a semiconductor memory is appropriately mounted, and a computer program read from them is loaded. It is installed in the storage unit 723 as necessary.

  When the above-described series of processing is executed by software, a program constituting the software is installed from a network or a recording medium.

  For example, as shown in FIG. 25, this recording medium is distributed to distribute a program to a user separately from the apparatus main body, and includes a magnetic disk (including a flexible disk) on which a program is recorded, an optical disk ( CD-ROM, DVD (including), magneto-optical disk (including MD), or removable media 321 composed of semiconductor memory, etc., as well as being distributed to users in a pre-installed state in the device body. A ROM 712 in which a program is recorded and a hard disk included in the storage unit 723 are configured.

  In the present specification, the step of describing the program recorded on the recording medium is not limited to the processing performed in chronological order according to the described order, but is not necessarily performed in chronological order. It also includes processes that are executed individually.

  Further, in this specification, the system represents the entire apparatus composed of a plurality of devices (apparatuses).

  In the above, the configuration described as one device may be divided and configured as a plurality of devices. Conversely, the configurations described above as a plurality of devices may be combined into a single device. Of course, configurations other than those described above may be added to the configuration of each device. Furthermore, if the configuration and operation of the entire system are substantially the same, a part of the configuration of a certain device may be included in the configuration of another device. That is, the embodiment of the present invention is not limited to the above-described embodiment, and various modifications can be made without departing from the gist of the present invention.

It is a figure which shows the structural example of the information processing system to which this invention is applied. It is a figure which shows the example of a display of an enzyme network. It is a figure which shows the detailed structural example of the simulation process part 111 of FIG. It is a flowchart explaining the example of the flow of a simulation process. It is a flowchart explaining the example of the flow of an allocation amount setting process. It is a flowchart explaining the example of the flow of discharge amount calculation processing. It is a figure which shows the structural example of an enzyme network. It is a figure which shows a simulation result. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the simulation result of the enzyme network 200 of FIG. It is a figure which shows the structural example of a pentose phosphate circuit. It is a figure which shows the simulation result of the pentose phosphate circuit. It is a figure which shows the simulation result of the pentose phosphate circuit. It is a figure which shows the simulation result of the pentose phosphate circuit. It is a figure which shows the simulation result of the pentose phosphate circuit. It is a figure which shows the simulation result of the pentose phosphate circuit. It is a figure which shows the simulation result of the pentose phosphate circuit. It is a figure which shows the structural example of a biofuel cell. It is a figure which shows the structural example of the personal computer to which this invention is applied.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 100 Information processing system, 101 Metabolic simulator, 102 Database, 111 Simulation processing part, 121 Enzyme network database, 122 Creation data database, 151 Calculation part, 152 Holding part, 161 Setting part, 162 Unnecessary path deletion part, 163 Enzyme allocation part, 164 discharge amount calculation unit, 165 maximum value specifying unit, 166 unused route deletion unit, 167 repetition control unit, 168 display control unit, 169 storage control unit

Claims (7)

An information processing device that simulates the state of metabolism from the starting material to the discharged material by an enzymatic reaction,
A composition ratio setting means for setting a composition ratio of each enzyme of the enzyme group to be simulated;
By simulating the enzyme reaction by each enzyme whose composition ratio is set by the composition ratio setting means using the Michaelis-Menten equation, the state of metabolism is simulated for the entire enzyme group, and An emission amount calculating means for calculating an emission amount after a predetermined time;
Repetitive control means for controlling the component ratio setting means and the discharge amount calculating means, and repeatedly calculating the discharge amount while changing the component ratio;
Maximum value specifying means for specifying a maximum value among a plurality of discharge amounts calculated by the control of the repetitive control means;
Unused enzyme deletion means for deleting an enzyme that has not been subjected to an enzyme reaction from the enzyme group when the discharge amount of the maximum value specified by the maximum value specifying means is calculated by the discharge amount calculation means; With
The repetitive control means controls the constituent ratio setting means and the discharge amount calculating means again for the enzyme group from which the unused enzymes are deleted by the unused enzyme deleting means, and changing the constituent ratio while changing the constituent ratio An information processing device that repeatedly calculates emissions. The information processing apparatus according to claim 1, wherein the component ratio setting unit sets a component ratio of an arbitrarily selected enzyme in a group of enzymes to be simulated to zero. From the enzyme group to be the target of the simulation, further comprising unnecessary enzyme deletion means for deleting unnecessary enzymes that do not contribute to metabolism from the starting material to the excretion material,
The information processing apparatus according to claim 1, wherein the component ratio setting unit sets a component ratio of each enzyme in the enzyme group after unnecessary enzymes are deleted by the unnecessary enzyme deletion unit. Under the control of the repetition means, the calculation of the discharge amount is repeated a predetermined number of times while the unused enzyme is deleted by the unused enzyme deletion means, and then the maximum of the discharge amount specified by the maximum value specifying means. The information processing apparatus according to claim 1, further comprising display control means for causing the display unit to display the value and the enzyme group when the maximum value is calculated as image information. Under the control of the repetition means, the calculation of the discharge amount is repeated a predetermined number of times while the unused enzyme is deleted by the unused enzyme deletion means, and then the maximum of the discharge amount specified by the maximum value specifying means. The information processing apparatus according to claim 1, further comprising a storage control unit that stores a value and an enzyme group when the maximum value is calculated in a storage unit. An information processing method of an information processing apparatus that simulates the state of metabolism from a starting material to an exhausted substance by an enzyme reaction,
Set the composition ratio of each enzyme in the enzyme group to be simulated,
By simulating the enzyme reaction by each enzyme with the composition ratio set using the Michaelis-Menten equation, the state of metabolism is simulated for the entire enzyme group, and the discharge of the discharge substance after a predetermined time Calculate the quantity,
Repeatedly calculating the emissions while changing the composition ratio,
Identify the maximum value from the repeatedly calculated emissions,
From the enzyme group when the specified maximum discharge amount is calculated, remove the enzyme that did not undergo the enzyme reaction,
Furthermore, for the enzyme group from which unused enzymes are deleted, the discharge amount is repeatedly calculated while changing the composition ratio. A computer that simulates the state of metabolism from the starting material to the effluent by the enzyme reaction,
Set the composition ratio of each enzyme in the enzyme group to be simulated,
By simulating the enzyme reaction by each enzyme with the composition ratio set using the Michaelis-Menten equation, the state of metabolism is simulated for the entire enzyme group, and the discharge of the discharge substance after a predetermined time Calculate the quantity,
Repeatedly calculating the emissions while changing the composition ratio,
Identify the maximum value from the repeatedly calculated emissions,
From the enzyme group when the specified maximum discharge amount is calculated, remove the enzyme that did not undergo the enzyme reaction,
Furthermore, the program which performs the process which repeatedly calculates the said discharge | emission amount, changing the said composition ratio about the enzyme group from which the unused enzyme was deleted.

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