DESCRIPTION METHOD OF PURIFYING AMIDE COMPOUND AQUEOUS SOLUTION AND PRODUCTION METHOD OF AMIDE COMPOUND 5 TECHNICAL FIELD The present invention relates to a method of purifying an amide compound aqueous solution obtained with a biocatalyst, and relates to a production method of an amide compound with a biocatalyst. 10 Priority is claimed on Japanese Patent Application No.2003-098139 filed on April 1, 2003, the content of which is incorporated herein by reference. BACKGROUND ART In recent years, a method of producing compounds with a biocatalyst having 15 enzyme activity has been used for many productions of compounds because there are some advantages such that reaction processes can be simplified due to mild reaction conditions, and purity of reaction products becomes higher or purifying processes can be simplified due to there only being a small amount of by-product. The methods of producing compounds with a biocatalyst and also a method of 20 producing aide compounds have been extensively investigated since the finding of an enzyme, nitrile hydratase, which converts a nitrile compounds to amide compounds. Methods of producing amide compounds with a biocatalyst are, for example, disclosed in Japanese Unexamined Patent Application, First Publication No. 54-129190, Japanese Unexamined Patent Application, First Publication No. 54-143592, Japanese Unexamined 25 Patent Application, First Publication No. 61-162193, Japanese Unexamined Patent Application, First Publication No. 2-000470, Japanese Unexamined Patent Application, First Publication No. 5-103681, Japanese Unexamined Patent Application, First Publication No. 11-089575, Japanese Unexamined Patent Application, First Publication No. 11-123098, or the like. 30 The methods of producing amide compounds with a biocatalyst have now been employed in industrial production of acrylamide, nicotinamide, or the like as superior reaction processes in view of operativity, safety, economy, and the like. Accordingly, a method of separating a biocatalyst from an aqueous solution 2 containing an aide compound (reaction liquid) obtained with a biocatalyst has also been investigated. Examples of separation methods of a biocatalyst from an amide compound aqueous solution include a filtration method using a hollow fiber membrane disclosed in Japanese Examined Patent Application, Second Publication No. 5-049273 5 and a method of removing the biocatalyst with air bubbles disclosed in Japanese Unexamined Patent Application, First Publication No. 2001-078749. However, when the amide compound is produced with a biocatalyst in the aqueous medium, an expandable impurity (expandable component) remains in the amide compound aqueous solution even if the biocatalyst is separated from the aide 10 compound aqueous solution. If the aqueous solution amide compound has expandability, bubbling may occur in the aide compound aqueous solution in subsequent processes or handling (for example, during transport or when filling the amide compound aqueous solution into a container). Accordingly, there are problems such that the handling of the amide compound aqueous solution is difficult and the 15 efficiency of handling operation is deteriorated. When the amide compound is an acrylamide, the following problems have occurred. When polyacrylamide is produced with acrylamide, nitrogen gas is blown into the acrylamide aqueous solution in order to reduce a dissolved oxygen concentration, If the acrylamide aqueous solution has expandability, a larger container may be required 20 to prevent overflowing of bubbles or spurting of bubbles. In view of the above-described problems, an amide compound aqueous solution having small expandability has been desired. As a method of producing the aide compound aqueous solution having small expandability, the present inventors have proposed a method for decreasing the amount 25 of microorganism biomass to be used disclosed in Japanese Unexamined Patent Application, First Publication No. 2001-299376, and a method for removing expandable components by forming air bubbles disclosed in Japanese Unexamined Patent Application, First Publication No. 2001-078749. However, the amount of biomass to be used is sometimes determined according 30 to catalyst performance, and when the amide compound is produced using an economical amount of catalyst; it is difficult to sufficiently reduce expandability. The method for removing expandable components by forming air bubbles is extremely efficient in terms of removing expandable components; therefore, the method 3 is suitably used. However, the method for removing expandable components by forming air bubbles requires a special device, and skill in controlling the ratio of gas/liquid to be supplied is required to stably remove expandable components. A method of purifying an acrylamide aqueous solution using an ultrafiltration 5 membrane is disclosed in Japanese Unexamined Patent Application, First Publication No. 55-062054. According to the method, impurities (acrylamide oligomer or crosslinkable material) in the acrylamide aqueous solution are removed, however, the acrylamide aqueous solution is produced by a copper catalyst method under a reaction conditions by which impurities of acrylamide tend to be generated. Even if the method 10 is simply applied to the acrylamide aqueous solution obtained with the biocatalyst, expandable impurities cannot be sufficiently separated. A method of purifying an acrylamide aqueous solution using a biocatalyst with an ultrafiltration membrane has not been reported. Recently, an expandable component derived from a biocatalyst has not been investigated, and furthermore, nothing is known 15 about a relationship between molecular weight cutoff of the ultrafiltration membrane and removal property of the expandable component. Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. 20 DISCLOSURE OF THE INVENTION It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. An object of a preferred form of the present invention is to provide a method of purifying an amide compound aqueous solution in which an amide compound aqueous 25 solution having fewer impurities and a small expandability is obtained, and a process for producing an amide compound. The present inventors anticipated that an expandable component is polysaccharides, proteins, or complexes thereof derived from organisms, and have intensively researched and have found that, unexpectedly, the expandable component 30 can be removed by using an ultrafiltration membrane having a molecular weight cutoff of less than 10000.
4 A method of purifying an amide compound aqueous solution according to the present invention comprises filtering an aqueous solution containing an amide compound obtained with a biocatalyst using an ultrafiltration membrane having a molecular weight cutoff of 1000 or more and less than 10000. 5 According to the present invention, an amide compound aqueous solution comprising a small amount of impurities and small expandability can be obtained. In the method of purifying an amide compound aqueous solution according to the present invention, the ultrafiltration membrane may have a molecular weight cutoff of 1000 or more and less than 5000. 10 The amide compound may be acrylamide or nicotinamide. The biocatalyst may be a microorganism biomass, immobilized biomass, or immobilized enzyme. An amide compound aqueous solution according to the present invention comprises an amide compound obtained with a biocatalyst, and is produced by filtering 15 with an ultrafiltration membrane having a molecular weight cutoff of 1000 or more and less than 10000. A production method of an amide compound according to the present invention comprises; converting a nitrile compound to an amide compound with a biocatalyst in an aqueous medium, and filtering an aqueous solution containing an amide compound using 20 an ultrafiltration membrane having a molecular weight cutoff of 1000 or more and less than 10000. Unless the context clearly requires otherwise, throughout the description and the claims, the words "comprise", "comprising", and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the 25 sense of "including, but not limited to". BEST MODE FOR CARRYING OUT THE INVENTION Preferred examples of the present invention are explained below, however, the present invention is not limited to the following examples. An amide compound aqueous solution according to the present invention is 30 obtained by a purification method of filtering an aqueous solution containing an amide compound obtained with a biocatalyst using an ultrafiltration membrane having a molecular weight cutoff of 1000 or more and less than 10000. Specifically, the amide 4a compound aqueous solution is produced by a reaction step to convert a nitrile compound to an amide compound with the biocatalyst in an aqueous medium, and a purification step to filter an aqueous solution containing the amide compound (reaction liquid) using the ultrafiltration membrane. 5 The "aqueous medium" described in the present invention is defined as an aqueous solution using water as a solvent. The aqueous medium comprises dispersions in which a liquid or solid material undissolved in the aqueous solution is dispersed in water or the aqueous solution. The "biocatalyst" described in the present invention is defined as a catalyst 10 comprising an enzyme having a catalyst capacity. Examples of the biocatalyst include 5 enzymes themselves, microorganism biomasses or cells containing an enzyme, and enzymes, biomasses, or cells immobilized by an entrapment method, cross-linking method, carrier bonding method, or the like. Among these, microorganism bionasses, immobilized biomasses, or immobilized enzymes are suitable because catalyst addition, 5 catalyst concentration control, catalyst separation, and the like are easily carried out. Examples of immobilized carriers for immobilizing enzymes, biomasses, and cells include glass beads, silica gel, polyurethane, polyacrylamide, polyvinyl alcohol, carageenan, alginic acid, agar, gelatin, and the like. The "catalyst capacity" described in the present invention is defined as a 10 capacity for converting a nitrile compound to an amide compound by hydration. An enzyme comprising such a capacity is generally referred to as nitrile hydratase. Nitrile hydratase has been found in various microorganisms. As microorganism species having nitrile hydratase activity, for example, Bacillus genus, Bacteridium genus, Micrococcus genus, and Brevibacterium genus (see 15 Japanese Examined Patent Application, Second Publication No. 62-021519); Corynebacterium genus and Nocardia genus (see Japanese Examined Patent Application, Second Publication No. 56-017918); Pseudomonas genus (see Japanese Examined Patent Application, Second Publication No. 59-037951); and Rhodococcus genus and Microbacterium genus (see Japanese Examined Patent Application, Second Publication 20 No. 4-004873) are known. The amide compound according to the present invention is not limited if the amide compound is converted from a nitrile compound by the effect of nitrile hydratase. Examples of nitrile compounds include aliphatic saturated nitriles such as acetonitrile, propionitrile, succinonitrile, and adiponitrile; aliphatic unsaturated nitriles such as 25 acrylonitrile and methacrylonitrile; aromatic nitriles such as benzonitrile and phthalodinitrile; heterocyclic nitriles such as 3-cyanopyridine and 2-cyanopyridine; and the like. Typical examples of amide compounds suited to production with the biocatalyst include propionamide, acrylamide, methacrylamide, and nicotinamide in view of superior 30 chemical and physical properties and economical reasons, and especially, acrylamide and nicotinamide are suitably used. Examples of reactors used in the reaction steps include a fixed bed, a moving bed, a fluidized bed,. an agitation vessel, or the like. Either of a batch reaction type 6 reactor and a continuous reaction type reactor can be selected. A reaction pattern is selected according to properties of reaction substrates (nitrile compounds), reaction liquids, objective compounds (amide compounds), or the like or production scale, and a reactor is suitably selected. For example, when 5 production with a continuous reaction is carried out, the biocatalyst often undergoes reaction inhibition or deactivation by reaction substrates or reaction products, and a reactor which can easily control reaction temperature and pH is preferably selected. Therefore, a multi continuous agitation vessel in which two or more agitation vessels are continuously connected is preferred. 10 The ultrafiltration membrane used in the purification step has a molecular weight cutoff of 1000 or more and less than 10000. If the ultrafiltration membrane has a molecular weight cutoff of less than 10000, polysaccharides, proteins, and complexes thereof derived from organisms as expandable components can be removed. The ultrafiltration membrane preferably has a molecular weight cutoff of less than 5000 to 15 completely remove expandable components. It is preferable that the molecular weight cutoff of the ultrafiltration membrane is decreased in view of removing a large amount of impurities. However, as the molecular weight cutoff decreases, filtration velocity generally becomes slower; as a result, a large filtration device is required. Therefore, an ultrafiltration membrane in 20 which a suitable filtration velocity for industrial production of aide compounds is obtained has a molecular weight cutoff of 1000 or more. The ultrafiltration membrane having 1000 or more and less than 10000 of molecular weight cutoff described in the present invention has a rejection rate of ca-lactalbumin having a molecular weight of 14200 of 85% or more under the condition 25 that specific absorption to the membrane is not carried out. Furthermore, the ultrafiltration membrane having a molecular weight cutoff of 1000 or more and less than 5000 has a rejection rate of inorganic salts dissolved in water and the above-described amide compound of 5% or less, and also has a rejection rate of a-lactalbumin having a molecular weight of 14200 of 90% or more. 30 The "rejection rate" is calculated by the following formula. (Concentration of treated water after filtration) / (concentration of raw water before filtration) x 100 (%) Usually, the rejection rate is measured with a low concentration aqueous solution of 7 about 100 mg/L. If the rejection rate changes with the passage of time, an adoptable value of the rejection rate is not a value just when starting treatment but a value when stabilized by repeating filtration treatment. In the present invention, to efficiently remove the expandable component, 5 another well-known purification method can be performed before the treatment with the ultrafiltration membrane. Examples The present invention is explained in detail with reference to examples below. (Example 1 and Comparative Example 1; Preparation of Biocatalyst) 10 Rhodococcus rhodochrous J1 (FERM BP-1478) having nitrile hydratase activity was aerobically cultured on culture medium (pH 7.0) including 2% by mass of glucose, 1% by mass of urea, 0.5% by mass of peptone, 0.3% by mass of yeast extract, and 0.05% by mass of cobalt chloride at 30"C. The cultured FERM BP-1478 was washed with 50 mM phosphate buffer (pH 7.0) to obtain a biomass suspension (15% by mass of dried 15 biomass). (Reaction of 3-cyanopyridine to nicotinamide with biomass) 1 L of 15% by mass of 3-cyanopyridine aqueous solution (50 mM phosphate buffer, pH 7) was poured into a 5-L glass beaker, 25 mL of the prepared biomass suspension was added the glass beaker, and then the mixture was gently stirred in a water 20 bath at 30*C. After reaction for 24 hours, a 17% by mass nicotinamide aqueous solution was obtained. The nicotinamide aqueous solution was filtered with a membrane filter having a 0.45 pm pore size (manufactured by Advantec Toyo Kaisha, Ltd., Mixed cellulose ester type, 47 nunt) to obtain a transparent nicotinamide aqueous solution (sample 1). 25 (Purification of reaction liquid) The obtained nicotinamide aqueous solution was filtered with an ultrafiltration membrane having a molecular weight cutoff of 3000 (manufactured by Pall corporation, OS003C 11, a-albumin nominal rejection rate: 96% or more) to obtain a purified nicotinamide aqueous solution (sample 2). 30 (Evaluations) 20 mL of each obtained sample was poured into a 24 mm4 test tube and the test tube was capped with a silicon rubber stopper. The test tube was agitated by hand to expand the sample and then was left to stand, and the tirne till the bubbles burst was 8 measured. The results are shown in Table 1. Table 1 Time till bubbles Sample Filtration burst Molecular weight cutoff: Example 1 Sample 2 3000 3 seconds 3000 Comparative Sample 1 0.45 pm 12 seconds Example 1 5 (Examples 2, 3, and 4, Comparative Examples 2 and 3: Preparation of Biocatalyst) A biomass suspension (15% by mass of dried biomass) of Rhodococcus rhodochrous JI (FERM BP-1478) having nitrile hydratase activity was similarly obtained as in Example 1. Furthermore, a monomer aqueous solution comprising 30% by mass of 10 acrylamide, 1% by mass of methylene bisacrylamide, and 4% by mass of 2-dimethylaminopropyl methacrylamide was prepared. Subsequently, the biomass suspension, the monomer aqueous solution, 10% by mass of an N,N,N',N'-tetramethylethylenediamine aqueous solution, and 10% by mass of an ammonium persulfate aqueous solution were treated by line mixing at 5 L/hr, 2 L/hr, 15 0.1 L/hr, and 0.1 L/hr respectively, in that order. Each discharge liquid was poured in a vat of 300 x 300 x 30 mn in order, and the discharge liquid was polymerized with the monomer in the vat to obtain a biomass-immobilized gel sheet. The obtained biomass-immobilized gel sheet was cut to about 0.5 mm square with a knife to obtain immobilized biomass particles. The immobilized biomass 20 particles were washed by running 0.1% by mass of a sodium acrylate aqueous solution (which was adjusted to pH 7) while fluidizing to obtain an immobilized biomass catalyst. (Reaction of acrylonitrile to acrylamide with immobilized biomass catalyst) 3510 g of a 0.2 g/L sodium acrylate aqueous solution was poured into a separable flask with ajacket of 5 L and 3 g of the above-described immobilized biomass 25 catalyst was added the separable flask. The mixture was stirred by two stirring blades made of a flat plate of 120 mm length and 20 mm width at a speed of 80 rpm while maintaining the pH at 7.0 and temperature at 10*C. Acrylonitrile was continuously fed 9 to this mixture so that the concentration of acrylonitrile in the mixture was always kept at 2% by mass, and an accumulative reaction was carried out till the concentration of acrylonitrile became 40% by mass. Subsequently, feeding of acrylonitrile was stopped and the reaction was 5 maintained till no acrylonitrile was detected in the reaction liquid. The immobilized biomass catalyst was separated from the reaction liquid with a 300 im of opening of metal gauze to obtain an acrylamide aqueous solution containing about 40% by mass of acrylamide (sample 3). (Purification of reaction liquid) 10 The obtained acrylamide aqueous solution was filtered with an ultrafiltration membrane having a molecular weight cutoff of 10000 (manufactured by Pall corporation, OSO10CI 1, a-albumin nominal rejection rate: 80% or less) to obtain a purified acrylamide aqueous solution (sample 4). Similarly, an unpurified acrylamide aqueous solution was filtered with an 15 ultrafiltration membrane having a molecular weight cutoff of 5000 (manufactured by Pall corporation, OS005C11, a-albumin nominal rejection rate: 96% or more) to obtain a purified acrylamide aqueous solution (sample 5). Similarly, an unpurified acrylamide aqueous solution was filtered with an ultrafiltration membrane having a molecular weight cutoff of 3000 (manufactured by Pall 20 corporation, OS003C11, a-albumin nominal rejection rate: 96% or more) to obtain a purified acrylamide aqueous solution (sample 6). Similarly, an unpurified acrylamide aqueous solution was filtered with an ultrafiltration membrane having a molecular weight cutoff of 1000 (manufactured by Pall corporation, OSOOIC 11) to obtain a purified acrylamide aqueous solution (sample 7). 25 (Evaluations) 50 mL of each obtained sample was poured into a graduated cylinder of 100 mL and air was passed into the graduated cylinder from the bottom thereof with a Kinoshita-type glass ball filter (G-3) at 20 mL/min to expand the sample, and the height of bubbles was measured. The results are shown in Table 2. 30 10 Table 2 Sample Filtration Height of bubbles Comparative Sample 3 None 130 mm Example 2 Molecular weight Compa e Sample 4 cut off 120 mm Example 3100 10000 Molecular weight Example 2 Sample 5 cut off 60 mm 5000 Molecular weight Example 3 Sample 6 cut off 13 mm 3000 Molecular weight Example 4 Sample 7 cut off 13 mm 1000 INDUSTRIAL APPLICABILITY The method of purifying an aide compound aqueous solution of the present 5 invention is a method of filtering an aqueous solution containing an amide compound obtained with a biocatalyst with an ultrafiltration membrane having a molecular weight cutoff of 1000 or more and less than 10000, so that an amide compound aqueous solution having a small amount of impurities and small expandability can be obtained.