JP5878313B2 - How to handle or store 3-hydroxypropionic acid solution - Google Patents
How to handle or store 3-hydroxypropionic acid solution Download PDFInfo
- Publication number
- JP5878313B2 JP5878313B2 JP2011160924A JP2011160924A JP5878313B2 JP 5878313 B2 JP5878313 B2 JP 5878313B2 JP 2011160924 A JP2011160924 A JP 2011160924A JP 2011160924 A JP2011160924 A JP 2011160924A JP 5878313 B2 JP5878313 B2 JP 5878313B2
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- Prior art keywords
- hydroxypropionic acid
- solution
- mass
- acid
- hydroxypropionic
- Prior art date
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- ALRHLSYJTWAHJZ-UHFFFAOYSA-N 3-hydroxypropionic acid Chemical compound OCCC(O)=O ALRHLSYJTWAHJZ-UHFFFAOYSA-N 0.000 title claims description 372
- 238000000034 method Methods 0.000 claims description 48
- 238000000855 fermentation Methods 0.000 claims description 31
- 230000004151 fermentation Effects 0.000 claims description 31
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 26
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 238000004519 manufacturing process Methods 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 238000003860 storage Methods 0.000 claims description 17
- 150000001412 amines Chemical class 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 6
- 150000003863 ammonium salts Chemical class 0.000 claims description 6
- 150000007524 organic acids Chemical class 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
- 229910052698 phosphorus Inorganic materials 0.000 claims description 6
- 239000011574 phosphorus Substances 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
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- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
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- 229910052708 sodium Inorganic materials 0.000 claims description 4
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 description 67
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
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- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 229960000723 ampicillin Drugs 0.000 description 3
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000000909 electrodialysis Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
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- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
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- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
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- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
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Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は、３−ヒドロキシプロピオン酸溶液の取扱い方法または保管の方法に関する。さらに３−ヒドロキシプロピオン酸溶液からのアクリル酸の製造方法に関する。 The present invention relates to a method for handling or storing a 3-hydroxypropionic acid solution. Furthermore, it is related with the manufacturing method of acrylic acid from 3-hydroxypropionic acid solution.
地球温暖化防止および環境保護の観点から、炭素源としてリサイクル可能な生物由来資源を従来の化石原料の代替として用いることが注目されている。例えば、汎用化成品、プラスチックおよび燃料生産の原料として、トウモロコシや小麦等の澱粉系バイオマス、サトウキビなどの糖質系バイオマス、および菜種の絞りかすや稲わら等のセルロース系バイオマス等のバイオマス資源を原料として利用する方法の開発が試みられている。また、バイオマス由来の糖類の利用以外にも、木質系バイオマスをガス化して得られる一酸化炭素と水素とを原料として利用する方法や、木質系バイオマスをガス化してメタノールを合成する方法についても検討・報告されている。このように、バイオマスから得られる糖類以外にも、様々な原料から汎用化成品を合成する技術が望まれている。 From the viewpoint of global warming prevention and environmental protection, attention has been focused on the use of biological resources that can be recycled as carbon sources as an alternative to conventional fossil raw materials. For example, as raw materials for general-purpose chemical products, plastics and fuel production, raw materials such as starch-based biomass such as corn and wheat, sugar-based biomass such as sugar cane, and cellulose-based biomass such as rapeseed pomace and rice straw Attempts have been made to develop methods for use as In addition to the use of biomass-derived saccharides, a method of using carbon monoxide and hydrogen obtained by gasifying woody biomass as raw materials and a method of synthesizing methanol by gasifying woody biomass are also studied. ·It has been reported. Thus, in addition to sugars obtained from biomass, a technique for synthesizing general-purpose chemical products from various raw materials is desired.
３−ヒドロキシプロピオン酸（３ＨＰとも称す）は、脂肪族ポリエステルの原料として有用な化合物であり、また、これから合成されるポリエステルは生分解性の地球にやさしいポリエステルとして注目されている。 3-Hydroxypropionic acid (also referred to as 3HP) is a useful compound as a raw material for aliphatic polyesters, and polyesters synthesized therefrom are attracting attention as biodegradable earth-friendly polyesters.
また３−ヒドロキシプロピオン酸は、脱水することによりアクリル酸を製造することができる。アクリル酸は、主にアクリル酸エステル製造の中間体として使用されており、アクリル酸エステルはコーティング剤、仕上げ剤、ペイント、接着剤の製造に使用され、吸着剤や洗浄剤用添加剤の製造にも使用されている。また、アクリル酸を部分中和させ、架橋性モノマーと共重合させることで吸水性樹脂を製造することもできる。アクリル酸の代替製造法としては、アクリロニトリルの硫酸による加水分解が知られている。しかし、この方法では、硫酸アンモニウム廃棄物が大量に生成し、それに伴うコストのために商業的には実施されていない。 Further, 3-hydroxypropionic acid can produce acrylic acid by dehydration. Acrylic acid is mainly used as an intermediate in the manufacture of acrylic esters, and acrylic esters are used in the manufacture of coating agents, finishes, paints, and adhesives, and in the manufacture of adsorbents and detergent additives. Has also been used. Moreover, a water absorbing resin can also be manufactured by partially neutralizing acrylic acid and copolymerizing with a crosslinkable monomer. As an alternative method for producing acrylic acid, hydrolysis of acrylonitrile with sulfuric acid is known. However, this process produces a large amount of ammonium sulfate waste and is not commercially implemented due to the associated costs.
３−ヒドロヒドロキシプロピオン酸は微生物の培養により生産可能なことが報告されている。例えば、特許文献１では、３−ヒドロキシプロピオン酸生成能を有さない大腸菌に遺伝子組換えにより３―ヒドロキシプロピオン酸生成能を付与し、得られた組換え微生物を３−ヒドロキシプロピオン酸の発酵生産に用いる方法が開示されている。 It has been reported that 3-hydrohydroxypropionic acid can be produced by culturing microorganisms. For example, in Patent Document 1, 3-hydroxypropionic acid-producing ability is imparted by genetic recombination to E. coli that does not have 3-hydroxypropionic acid-producing ability, and the resulting recombinant microorganism is produced by fermentation of 3-hydroxypropionic acid. A method used for the above is disclosed.
一方、非特許文献１および２では、３−ヒドロキシプロピオン酸生成能を元来保有する微生物を３−ヒドロキシプロピオン酸の発酵生産に用いる方法が開示されている。具体的に、非特許文献１では、Ｄｅｕｓｕｌｆｏｒｉｂｒｉｏ属細菌を用いて、非特許文献２では、Ｌａｃｔｏｂａｃｉｌｌｕｓ属細菌を用いて、３−ヒドロキシプロピオン酸の発酵生産が行われている。 On the other hand, Non-Patent Documents 1 and 2 disclose a method in which a microorganism that originally has 3-hydroxypropionic acid-producing ability is used for fermentation production of 3-hydroxypropionic acid. Specifically, in Non-Patent Document 1, fermentative production of 3-hydroxypropionic acid is performed using Deusforibrio bacteria, and in Non-Patent Document 2, using Lactobacillus bacteria.
また上記のような、３−ヒドロキシプロピオン酸を含んだ発酵液から、３−ヒドロキシプロピオン酸を取り出す方法も検討されており、例えば特許文献２では、３−ヒドロキシプロピオン酸のアンモニウム塩を含んだ液を、水に非混和性の有機アミンの存在下で加熱することにより、有機アミン相へ抽出し、さらに逆抽出することで、３−ヒドロキシプロピオン酸を分離することが開示されている。さらに特許文献３には、電気透析を用いた回収方法が開示されている。 Moreover, the method of taking out 3-hydroxypropionic acid from the fermentation liquid containing 3-hydroxypropionic acid as mentioned above is also examined, for example, in patent document 2, the liquid containing the ammonium salt of 3-hydroxypropionic acid Is extracted into an organic amine phase by heating in the presence of an organic amine immiscible in water, and further back-extracted to separate 3-hydroxypropionic acid. Further, Patent Document 3 discloses a recovery method using electrodialysis.
しかし、３−ヒドロキシプロピオン酸の発酵による製造や、その誘導体化の技術は未だ確立されておらず、工業化に当たっては技術のブラッシュアップが望まれている。 However, the production of 3-hydroxypropionic acid by fermentation and the derivatization technology have not been established yet, and it is desired to brush up the technology for industrialization.
本発明者らは、３−ヒドロキシプロピオン酸の合成、精製、誘導体化を検討する中で、３−ヒドロキシプロピオン酸は、分子間エステル化反応により二量体、三量体、四量体といったオリゴマーを形成しやすく、安定性に欠ける化合物であることを見出した。 The present inventors have studied synthesis, purification, and derivatization of 3-hydroxypropionic acid, and 3-hydroxypropionic acid is an oligomer such as a dimer, trimer, or tetramer by an intermolecular esterification reaction. It was found that the compound is easy to form and lacks stability.
本発明は、発酵にて得られた３−ヒドロキシプロピオン酸を含む溶液の取扱いまたは保管する際に、３−ヒドロキシプロピオン酸のオリゴマー化を抑制し、３−ヒドロキシプロピオン酸を誘導体化するために十分な品質を保持する３−ヒドロキシプロピオン酸溶液の取扱いまたは保管できる方法を提供することを目的とする。 The present invention is sufficient to suppress oligomerization of 3-hydroxypropionic acid and to derivatize 3-hydroxypropionic acid when handling or storing a solution containing 3-hydroxypropionic acid obtained by fermentation. It is an object of the present invention to provide a method capable of handling or storing a 3-hydroxypropionic acid solution having high quality.
本発明者らは、種々検討の結果、発酵により得られた３−ヒドロキシプロピオン酸を濃度１０〜９０質量％の濃度で含む溶液を取り扱うまたは保管するに当たり、溶液中の水の含有量が１０〜９０質量％でかつ５〜５０℃の範囲で取り扱うことまたは保管することを見出した。また３−ヒドロキシプロピオン酸を除く発酵由来の有機酸が３−ヒドロキシプロピオン酸に対して５０質量％以下で取り扱うことまたは保管すること、さらに３−ヒドロキシプロピオン酸に対して、リン、窒素、マグネシウム、カルシウム、ナトリウムおよびカリウムから選ばれる少なくとも１種以上の元素を含み、該元素の合計が、１０００質量ｐｐｍ以下で取り扱うことまたは保管することにより、３−ヒドロキシプロピオン酸溶液を安定に存在させることができ、３−ヒドロキシプロピオン酸の誘導体化も効率的に進行させることができることを見出した。 As a result of various studies, the present inventors handle or store a solution containing 3-hydroxypropionic acid obtained by fermentation at a concentration of 10 to 90% by mass. It was found to be handled or stored at 90 mass% and in the range of 5-50 ° C. Moreover, the organic acid derived from fermentation excluding 3-hydroxypropionic acid is handled or stored at 50% by mass or less with respect to 3-hydroxypropionic acid, and further, phosphorus, nitrogen, magnesium, By containing or storing at least one element selected from calcium, sodium and potassium, the total of which is 1000 ppm by mass or less, the 3-hydroxypropionic acid solution can be stably present. It was found that derivatization of 3-hydroxypropionic acid can also proceed efficiently.
本発明によれば３−ヒドロキシプロピオン酸溶液を安定に取扱いまたは保管することができる。また３−ヒドロキシプロピオン酸の誘導体化へ問題なく使用することができため、誘導体化反応の効率化や、安定化、コストダウンに寄与することができる。 According to the present invention, the 3-hydroxypropionic acid solution can be handled or stored stably. Moreover, since it can be used without problem for derivatization of 3-hydroxypropionic acid, it can contribute to the efficiency, stabilization and cost reduction of the derivatization reaction.
本発明は、発酵により生成した３−ヒドロキシプロピオン酸の二量体化、三量体化、四量体化等のオリゴマー化を抑制し、安定に存在させる方法である。３−ヒドロキシプロピオン酸溶液は、特に濃度が高くなると安定性が低下するため、高い濃度領域での安定性の保持が重要である。本発明の取扱い方法または保管の方法においては、３−ヒドロキシプロピオン酸の初期濃度が１０〜９０質量％の溶液の場合に効果的であり、２０質量％以上の時により効果的であり、３０質量％以上の時にさらに効果的であり、４０質量％以上の時に一層効果的であり、５０質量％以上の時により一層効果的である。１０質量％未満の場合は、濃度が薄いため、その後の誘導体化反応において、反応速度が遅くなったり、コストアップの要因となり好ましくない。また９０質量％を超える濃度では、安定性が著しく悪いため、安定に保管することは困難である。 The present invention is a method of suppressing the oligomerization such as dimerization, trimerization, and tetramerization of 3-hydroxypropionic acid produced by fermentation and allowing it to exist stably. Since the stability of the 3-hydroxypropionic acid solution decreases particularly when the concentration becomes high, it is important to maintain the stability in a high concentration region. The handling method or storage method of the present invention is effective when the initial concentration of 3-hydroxypropionic acid is 10 to 90% by mass, more effective when the concentration is 20% by mass or more, and 30% by mass. % Is more effective, more effective when it is 40% or more, and more effective when it is 50% or more. When the concentration is less than 10% by mass, the concentration is low, and therefore, the reaction rate in the subsequent derivatization reaction becomes slow or the cost increases, which is not preferable. Further, at a concentration exceeding 90% by mass, the stability is remarkably poor, and it is difficult to store stably.
またヒドロキシカルボン酸はカルボキシル基と水酸基を有するため、オリゴマー化しやすいと考えられがちであるが、例えば３−ヒドロキシプロピオン酸の異性体である乳酸と比較すると、３−ヒドロキシプロピオン酸の方がオリゴマー化しやすく、これは３−ヒドロキシプロピオン酸の水酸基は１級であるのに対し、乳酸の水酸基は２級であることを考えると、驚くべきことであり、そのため本法により３−ヒドロキシプロピオン酸溶液を安定に取り扱うことまたは保管することは、非常に重要である。 Hydroxycarboxylic acid has a carboxyl group and a hydroxyl group, and thus tends to be considered to be easily oligomerized. For example, compared with lactic acid, which is an isomer of 3-hydroxypropionic acid, 3-hydroxypropionic acid is oligomerized. This is surprising, considering that the hydroxyl group of 3-hydroxypropionic acid is primary, whereas the hydroxyl group of lactic acid is secondary. Stable handling or storage is very important.
本発明の３−ヒドロキシプロピオン酸溶液は、３−ヒドロキシプロピオン酸と溶媒を含む。溶媒としては３−ヒドロキシプロピオン酸を溶解すればよく、特に限定されないが、水、アルコール、炭化水素、エーテル、ケトン、エステル、アミン、アミドまたはこれらを組み合わせた溶媒を用いることができる。好適には水である。
特に水の濃度は、３−ヒドロキシプロピオン酸溶液の安定性には影響が大きく、水の濃度によって、３−ヒドロキシプロピオン酸のカルボキシル基の解離平衡がずれｐＨが変化すること、また水は３−ヒドロキシプロピオン酸がオリゴマー化する際の副生物でもあるため、水の濃度によって見かけの反応速度が変わることから、３−ヒドロキシプロピオン酸溶液の安定な取扱い方法または保管の方法においては、最適な範囲を選択する必要がある。本発明においては、水は３−ヒドロキシプロピオン酸溶液中に１０〜９０質量％存在することが好ましく、より好ましくは８０質量％以下であり、さらに好ましくは６０質量％以下である。
本発明における３−ヒドロキシプロピオン酸溶液の取扱い方法または保管の方法においては、温度は重要な要因である。温度が高すぎるとオリゴマー化速度が大きくなって好ましくないが、平衡的には温度が低い方がオリゴマー生成側に有利になるため、最適な温度範囲を選択する必要がある。本発明においては、５〜５０℃の範囲で、３−ヒドロキシプロピオン酸を取り扱うことまたは保管することが望ましい。５℃未満の場合、長期の保管の場合、平衡的にオリゴマーが増加する恐れがあり、また粘度が高くなるため取扱いに支障が出る場合がある。５０℃を超える温度では、オリゴマー化速度が大きくなり、短時間で安定性が低下する。
The 3-hydroxypropionic acid solution of the present invention contains 3-hydroxypropionic acid and a solvent. The solvent is not particularly limited as long as 3-hydroxypropionic acid is dissolved, and water, alcohol, hydrocarbon, ether, ketone, ester, amine, amide, or a combination of these can be used. Water is preferred.
In particular, the concentration of water has a great influence on the stability of the 3-hydroxypropionic acid solution. The dissociation equilibrium of the carboxyl group of 3-hydroxypropionic acid shifts and the pH changes depending on the concentration of water. Since hydroxypropionic acid is also a by-product of oligomerization, the apparent reaction rate changes depending on the concentration of water. Therefore, in the stable handling method or storage method of 3-hydroxypropionic acid solution, the optimum range is set. Must be selected. In the present invention, water is preferably present in the 3-hydroxypropionic acid solution in an amount of 10 to 90% by mass, more preferably 80% by mass or less, and further preferably 60% by mass or less.
In the method of handling or storing the 3-hydroxypropionic acid solution in the present invention, temperature is an important factor. If the temperature is too high, the oligomerization rate increases, which is not preferable. However, in terms of equilibrium, a lower temperature is advantageous for the oligomer production side, so it is necessary to select an optimal temperature range. In the present invention, it is desirable to handle or store 3-hydroxypropionic acid in the range of 5 to 50 ° C. When the temperature is lower than 5 ° C., the oligomer may increase in equilibrium in the case of long-term storage, and handling may be hindered because the viscosity increases. At temperatures exceeding 50 ° C., the oligomerization rate increases and the stability decreases in a short time.
発酵による３−ヒドロキシプロピオン酸の生成においては、使用する酵素や菌体、酵母等の微生物の種類や、原料、発酵条件によっても異なるが、副生成物として有機酸が生成することが多い。例えばギ酸、酢酸、プロピオン酸、酪酸、イソ酪酸、吉草酸、グリコール酸、乳酸、２−ヒドロキシ酪酸、３−ヒドロキシ酪酸、４−ヒドロキシ酪酸、２−ヒドロキシイソ酪酸、３−ヒドロキシイソ酪酸、コハク酸、ピルビン酸等が挙げられる。これらは３−ヒドロキシプロピオン酸と同様の有機酸のため、分離が難しい場合があり、発酵液から３−ヒドロキシプロピオン酸を回収した際に、不純物として含まれることが多い。 In the production of 3-hydroxypropionic acid by fermentation, an organic acid is often produced as a by-product, although it varies depending on the type of microorganisms used, such as enzymes, bacterial cells, and yeast, raw materials, and fermentation conditions. For example, formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, glycolic acid, lactic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid, succinic acid And pyruvic acid. Since these are organic acids similar to 3-hydroxypropionic acid, they may be difficult to separate and are often included as impurities when 3-hydroxypropionic acid is recovered from the fermentation broth.
これらの有機酸が不純物として含まれると、３−ヒドロキシプロピオン酸溶液の安定性は低下し、３−ヒドロキシプロピオン酸のオリゴマー化の速度が上がり、３−ヒドロキシプロピオン酸の濃度が低下する。そのため、３−ヒドロキシプロピオン酸を除く発酵由来の有機酸は３−ヒドロキシプロピオン酸に対して５０モル％以下であることが好ましい。より好ましくは４０モル％以下であり、一層好ましくは３０モル％以下であり、さらに好ましくは２０モル％以下であり、より一層好ましくは１０モル％以下である。 When these organic acids are contained as impurities, the stability of the 3-hydroxypropionic acid solution decreases, the speed of oligomerization of 3-hydroxypropionic acid increases, and the concentration of 3-hydroxypropionic acid decreases. Therefore, the organic acid derived from fermentation excluding 3-hydroxypropionic acid is preferably 50 mol% or less with respect to 3-hydroxypropionic acid. More preferably, it is 40 mol% or less, More preferably, it is 30 mol% or less, More preferably, it is 20 mol% or less, More preferably, it is 10 mol% or less.
また、発酵により３−ヒドロキシプロピオン酸を合成する際には、微生物の生育を促すために培地を添加する場合が多い。培地としては、天然物を使用したり、化学薬品を使用する。天然物としては例えば肉汁、ペプトン、酵母エキス、麦芽エキス、コーンミール、グルコース等が挙げられる。 Moreover, when synthesizing 3-hydroxypropionic acid by fermentation, a medium is often added to promote the growth of microorganisms. As the medium, natural products or chemicals are used. Examples of natural products include gravy, peptone, yeast extract, malt extract, corn meal, glucose and the like.
また化学薬品としては、例えば、リン酸水素二ナトリウム、リン酸二水素ナトリウム、リン酸水素二カリウム、リン酸二水素カリウム、塩化アンモニウム、塩化ナトリウム、塩化カリウム、塩化マグネシウム、塩化カルシウム、塩化鉄、硫酸マグネシウム、硫酸ナトリウム、硫酸マンガン、硫酸亜鉛、硫酸銅、パントテン酸、ニコチン酸、クエン酸、イノシトール等が挙げられる。 Examples of chemicals include disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, ammonium chloride, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, iron chloride, Examples thereof include magnesium sulfate, sodium sulfate, manganese sulfate, zinc sulfate, copper sulfate, pantothenic acid, nicotinic acid, citric acid, and inositol.
３−ヒドロキシプロピオン酸やこれらの培地成分を含んだ発酵液より、３−ヒドロキシプロピオン酸を回収する際、一部の培地成分が、混入する場合がある。中でも、リン、窒素、マグネシウム、カルシウム、ナトリウムおよびカリウムから選ばれる少なくとも１種以上の元素が含まれると、３−ヒドロキシプロピオン酸のオリゴマー化速度が大きくなり、安定性が損なわれる。そのため、３−ヒドロキシプロピオン酸溶液中のリン、窒素、マグネシウム、カルシウム、ナトリウムおよびカリウムの合計が、３−ヒドロキシプロピオン酸に対して、１０００質量ｐｐｍ以下が好ましい。より好ましくは７００質量ｐｐｍ以下である。 When 3-hydroxypropionic acid is recovered from a fermentation broth containing 3-hydroxypropionic acid and these medium components, some medium components may be mixed. Among these, when at least one element selected from phosphorus, nitrogen, magnesium, calcium, sodium and potassium is contained, the oligomerization rate of 3-hydroxypropionic acid is increased, and the stability is impaired. Therefore, the total of phosphorus, nitrogen, magnesium, calcium, sodium and potassium in the 3-hydroxypropionic acid solution is preferably 1000 ppm by mass or less with respect to 3-hydroxypropionic acid. More preferably, it is 700 mass ppm or less.
また、特にリンについては、リン酸やリン酸塩の形で存在すると、３−ヒドロキシプロピオン酸溶液の安定性の低下に大きく影響を及ぼすため、リン酸および／またはリン酸塩の形で存在するリンの量は、３−ヒドロキシプロピオン酸に対して、５００質量ｐｐｍ以下が好ましく、より好ましくは３００質量ｐｐｍ以下である。 In particular, phosphorus is present in the form of phosphoric acid and / or phosphate because the presence of phosphoric acid or phosphate greatly affects the stability of the 3-hydroxypropionic acid solution. The amount of phosphorus is preferably 500 ppm by mass or less, more preferably 300 ppm by mass or less, based on 3-hydroxypropionic acid.
また窒素については、アミンやアンモニウム塩の形で存在すると、３−ヒドロキシプロピオン酸溶液の安定性の低下に大きく影響を及ぼすため、アミンおよび／またはアンモニウム塩の形で存在する窒素の量は、３−ヒドロキシプロピオン酸に対して、５００質量ｐｐｍ以下が好ましく、より好ましくは３００質量ｐｐｍ以下である。 In addition, when nitrogen is present in the form of an amine or ammonium salt, it greatly affects the stability of the 3-hydroxypropionic acid solution, so the amount of nitrogen present in the form of amine and / or ammonium salt is 3 -500 mass ppm or less is preferable with respect to hydroxypropionic acid, More preferably, it is 300 mass ppm or less.
上記のような条件で取扱いまたは保管された３−ヒドロキシプロピオン酸溶液は、オリゴマー化もある程度抑制され、安定に存在することができる。３−ヒドロキシプロピオン酸溶液の取扱いとは、３−ヒドロキシプロピオン酸溶液の反応、物理的処理、化学的処理あるいは移送等を含む。また保管は、次の誘導体化工程までの間、タンクや容器中に貯蔵することを指す。上記のような条件で取扱いまたは保管された場合、３−ヒドロキシプロピオン酸溶液はその後の誘導体化においても問題なく使用可能である。安定性の目安は、次の誘導体化反応にもよるが、３−ヒドロキシプロピオン酸溶液中の３−ヒドロキシプロピオン酸のオリゴマーの濃度が３−ヒドロキシプロピオン酸の１００質量％以下で留まることが望ましい。３−ヒドロキシプロピオン酸のオリゴマーは、３−ヒドロキシプロピオン酸分子が２〜１０個結合したものが、オリゴマー全体の７０質量％以上であることが好ましく、８０質量％以上であることがより好ましい。さらに３−ヒドロキシプロピオン酸分子が２〜８個結合したものが、オリゴマー全体の７０質量％以上であることが好ましく、８０質量％以上であることがより好ましい。さらには３−ヒドロキシプロピオン酸分子が２〜５個結合したものが、オリゴマー全体の７０質量％以上であることが好ましく、８０質量％以上であることがより好ましい。３−ヒドロキシプロピオン酸溶液を上記条件に保持後、すぐに誘導体化反応する場合は、２４時間以上安定であれば良く、好ましくは４８時間以上である。３−ヒドロキシプロピオン酸溶液をある程度の期間、保管する場合は好ましくは１ヶ月以上、より好ましくは３ヶ月以上安定であればよい。 The 3-hydroxypropionic acid solution handled or stored under the conditions as described above can be stably present with oligomerization suppressed to some extent. The handling of the 3-hydroxypropionic acid solution includes reaction, physical treatment, chemical treatment or transfer of the 3-hydroxypropionic acid solution. Storage means storing in a tank or container until the next derivatization step. When handled or stored under the conditions as described above, the 3-hydroxypropionic acid solution can be used without problems in the subsequent derivatization. Although the standard of stability depends on the following derivatization reaction, it is desirable that the concentration of the oligomer of 3-hydroxypropionic acid in the 3-hydroxypropionic acid solution remains at 100% by mass or less of 3-hydroxypropionic acid. As for the oligomer of 3-hydroxypropionic acid, what 2-10 pieces of 3-hydroxypropionic acid molecules couple | bonded is preferable 70 mass% or more of the whole oligomer, and it is more preferable that it is 80 mass% or more. Furthermore, it is preferable that what couple | bonded with 2-8 3-hydroxypropionic acid molecules is 70 mass% or more of the whole oligomer, and it is more preferable that it is 80 mass% or more. Furthermore, it is preferable that the thing which 2-5 5-hydroxypropionic acid molecules couple | bonded is 70 mass% or more of the whole oligomer, and it is more preferable that it is 80 mass% or more. When the derivatization reaction is performed immediately after maintaining the 3-hydroxypropionic acid solution under the above conditions, it may be stable for 24 hours or more, and preferably 48 hours or more. When the 3-hydroxypropionic acid solution is stored for a certain period of time, it should preferably be stable for 1 month or longer, more preferably 3 months or longer.
以下、３−ヒドロキシプロピオン酸を誘導体化する例として、３−ヒドロキシプロピオン酸溶液を気相で脱水することによるアクリル酸の製造について例示するが、それ以外の液相での反応等、他の方法にも、本発明で得られた３−ヒドロキシプロピオン酸溶液は原料として使用できる。 Hereinafter, as an example of derivatizing 3-hydroxypropionic acid, production of acrylic acid by dehydrating a 3-hydroxypropionic acid solution in the gas phase will be exemplified, but other methods such as reaction in other liquid phases, etc. In addition, the 3-hydroxypropionic acid solution obtained in the present invention can be used as a raw material.
アクリル酸の製造に使われる３−ヒドロキシプロピオン酸を含む原料組成物は、上記の取扱い方法または保管の方法を経て得られた３−ヒドロキシプロピオン酸溶液をそのまま脱水反応の原料としても良いし、さらに濃度調整や溶媒や添加物等の添加によって、原料組成物を調製できる。
本発明における３−ヒドロキシプロピオン酸を含む原料組成物は、３−ヒドロキシプロピオン酸を含んでいれば良い。発酵やその後の回収工程、取扱いや保管中に生成する３−ヒドロキシプロピオン酸のダイマー等のオリゴマー類は、３−ヒドロキシプロピオン酸に対して１００質量％以下であれば使用可能である。原料組成物に含まれる３−ヒドロキシプロピオン酸の濃度は５〜９５質量％、好ましくは１０〜９０質量％、より好ましくは２０〜９０質量％である。
The raw material composition containing 3-hydroxypropionic acid used for the production of acrylic acid may use the 3-hydroxypropionic acid solution obtained through the above handling method or storage method as it is as a raw material for the dehydration reaction. The raw material composition can be prepared by adjusting the concentration or adding a solvent or an additive.
The raw material composition containing 3-hydroxypropionic acid in the present invention only needs to contain 3-hydroxypropionic acid. Oligomers such as dimers of 3-hydroxypropionic acid generated during fermentation, subsequent recovery steps, handling and storage can be used as long as they are 100% by mass or less based on 3-hydroxypropionic acid. The concentration of 3-hydroxypropionic acid contained in the raw material composition is 5 to 95% by mass, preferably 10 to 90% by mass, more preferably 20 to 90% by mass.
３−ヒドロキシプロピオン酸を含む原料組成物には溶媒が含まれていてもよい。溶媒としては、３−ヒドロキシプロピオン酸を溶解すればよく、特に限定されないが、水、アルコール、炭化水素、エーテル、ケトン、エステル、アミン、アミドまたはこれらを組み合わせた溶媒を用いることができる。好適には水である。 The raw material composition containing 3-hydroxypropionic acid may contain a solvent. The solvent is not particularly limited as long as 3-hydroxypropionic acid can be dissolved, but water, alcohol, hydrocarbon, ether, ketone, ester, amine, amide, or a combination of these can be used. Water is preferred.
本発明において原料組成物に溶媒を用いる場合、溶媒の濃度は５〜９５質量％であり、好ましくは１０〜９０質量％、より好ましくは１０〜８０質量％である。５質量％以上であれば、粘度の低下により原料組成物の取扱いが容易になり、また気化した溶媒の同伴によって３−ヒドロキシプロピオン酸の蒸発が促進される効果が期待できる。一方９５質量％以下とすることで、蒸発にかかる熱量を抑制し、用役費の低減に寄与できる。 In the present invention, when a solvent is used for the raw material composition, the concentration of the solvent is 5 to 95% by mass, preferably 10 to 90% by mass, and more preferably 10 to 80% by mass. If it is 5 mass% or more, the handling of a raw material composition becomes easy by the fall of a viscosity, and the effect by which evaporation of 3-hydroxypropionic acid is accelerated | stimulated by accompanying with the vaporized solvent can be anticipated. On the other hand, by setting it to 95% by mass or less, it is possible to suppress the amount of heat required for evaporation and contribute to the reduction of utility costs.
脱水反応においては、上記原料組成物を気化させた後、脱水触媒と接触させてアクリル酸を製造する。原料組成物の気化は、気化器にて原料組成物を蒸発させた後、脱水反応器に供給しても良いし、脱水反応器の上部に気化器を接続して一体化しても良い。 In the dehydration reaction, the raw material composition is vaporized and then brought into contact with a dehydration catalyst to produce acrylic acid. For vaporizing the raw material composition, the raw material composition may be evaporated in a vaporizer and then supplied to the dehydration reactor, or may be integrated by connecting a vaporizer to the upper portion of the dehydration reactor.
脱水工程で使用する反応器は、中に固体触媒を保持し、加熱することができればよく、固定床式流通反応器や流動床式流通反応器等が使用できる。固定床式反応器は、反応器内に触媒を充填して加熱しておき、そこに原料組成物の蒸気を供給すればよい。原料組成物の蒸気は、上昇流、下降流、水平流いずれも好適に使用できる。また熱交換の容易さから、多管式固定床反応器が好適に使用できる。
流動床式反応器は、反応器の中に粒状の触媒を入れ、原料組成物の蒸気や、別途供給する不活性ガス等で触媒を流動させながら反応させることができる。触媒が流動しているため、重質分による閉塞が起こりにくい。また触媒の一部を連続的に抜き出して、新しい触媒や再生した触媒を連続的に供給することもできる。
The reactor used in the dehydration step only needs to be able to hold and heat the solid catalyst therein, and a fixed bed flow reactor, a fluidized bed flow reactor, or the like can be used. In the fixed bed reactor, the catalyst is charged in the reactor and heated, and the raw material composition vapor is supplied thereto. As the vapor of the raw material composition, any of an upward flow, a downward flow and a horizontal flow can be suitably used. A multitubular fixed bed reactor can be preferably used because of easy heat exchange.
In a fluidized bed reactor, a granular catalyst is placed in the reactor, and the reaction can be carried out while fluidizing the catalyst with the vapor of the raw material composition or an inert gas supplied separately. Since the catalyst is flowing, clogging due to heavy components hardly occurs. It is also possible to continuously extract a part of the catalyst and continuously supply a new catalyst or a regenerated catalyst.
脱水反応の触媒は、３−ヒドロキシプロピオン酸をアクリル酸に転化する触媒作用を有するものであれば特に限定されず、ゼオライト等の結晶性メタロシリケート；カオリナイト、ベントナイト、モンモリロナイトなどの天然または合成粘土化合物；硫酸、ヘテロポリ酸、リン酸またはリン酸塩（リン酸のアルカリ金属塩、アルカリ土類金属塩、リン酸マンガン、リン酸ジルコニウム等）をアルミナやシリカ等の担体に担持させた触媒；活性アルミナ、ＳｉＯ２、ＴｉＯ２、ＺｒＯ２、ＳｎＯ２、Ｖ２Ｏ５、ＳｉＯ２−Ａｌ２Ｏ３、ＳｉＯ２−ＴｉＯ２、ＳｉＯ２−ＺｒＯ２、ＴｉＯ２−ＷＯ３、ＴｉＯ２−ＺｒＯ２などの無機酸化物または無機複合酸化物；ＭｇＳＯ４、Ａｌ２（ＳＯ４）３、Ｋ２ＳＯ４、ＡｌＰＯ４、Ｚｒ（ＳＯ４）２等の金属の硫酸塩、リン酸塩などの固体酸性物質；を挙げることができる。また酸化カルシウム、酸化マグネシウム等の固体塩基性物質も挙げられる。 The catalyst for the dehydration reaction is not particularly limited as long as it has a catalytic action for converting 3-hydroxypropionic acid into acrylic acid; crystalline metallosilicates such as zeolite; natural or synthetic clays such as kaolinite, bentonite and montmorillonite Compound: Catalyst in which sulfuric acid, heteropoly acid, phosphoric acid or phosphate (alkali metal phosphate, alkaline earth metal salt, manganese phosphate, zirconium phosphate, etc.) is supported on a support such as alumina or silica; activity alumina, SiO 2, TiO 2, ZrO 2, SnO 2, V 2 O 5, SiO 2 -Al 2 O 3, SiO 2 -TiO 2, SiO 2 -ZrO 2, TiO 2 -WO 3, TiO 2 -ZrO 2 inorganic oxides or inorganic composite oxides such as; MgSO 4, Al 2 (SO 4) 3, K 2 SO 4, lPO 4, Zr (SO 4) 2 and the like of metal sulfate, a solid acidic substances such as phosphates; and the like. Moreover, solid basic substances, such as calcium oxide and magnesium oxide, are also mentioned.
触媒層の温度は１５０〜５００℃に保持することが好ましい。好ましくは２００〜４５０℃である。この温度範囲であると、反応速度が速く、副反応も生じにくくアクリル酸の収率が高くなる。また反応圧力は特に限定されないが、原料組成物の蒸発方法、脱水反応の生産性や脱水反応後の捕集効率等を勘案して決定することができる。例えば反応圧力としては１０〜１０００ｋＰａであり、好ましくは５０〜３００ｋＰａである。 The temperature of the catalyst layer is preferably maintained at 150 to 500 ° C. Preferably it is 200-450 degreeC. Within this temperature range, the reaction rate is fast, side reactions are unlikely to occur, and the yield of acrylic acid is increased. The reaction pressure is not particularly limited, but can be determined in consideration of the evaporation method of the raw material composition, the productivity of the dehydration reaction, the collection efficiency after the dehydration reaction, and the like. For example, the reaction pressure is 10 to 1000 kPa, preferably 50 to 300 kPa.
本発明において、反応生成物を冷却してアクリル酸を含む組成物を得る方法としては、特に限定されるものではないが、例えば、反応生成ガスを熱交換器に導入し反応生成ガスの露点以下の温度で凝縮して得る方法や、または反応生成ガスを溶剤等の捕集剤に接触させて吸収する方法等により冷却して、アクリル酸を含む組成物を得ることができる。 In the present invention, the method of cooling the reaction product to obtain a composition containing acrylic acid is not particularly limited. For example, the reaction product gas is introduced into a heat exchanger and the reaction product gas has a dew point or less. The composition containing acrylic acid can be obtained by cooling by a method obtained by condensing at a temperature of, or a method of absorbing a reaction product gas by contacting it with a collection agent such as a solvent.
このようにして得られた反応生成物の組成物中には主な反応生成物である水、アクリル酸が含まれており、その他に副生物や原料組成物中の溶媒や不純物が含まれる場合がある。溶媒が水の場合は、アクリル酸の水溶液の状態で重合物製造の原料とすることができる。また精製工程を加えることにより高純度のアクリル酸にすることができる。精製工程は、蒸発、蒸留、抽出、膜分離、晶析等公知の技術により実施でき、それらを組み合わせて実施しても良い。 The reaction product composition thus obtained contains water and acrylic acid, which are the main reaction products, and contains by-products and solvents and impurities in the raw material composition. There is. When the solvent is water, it can be used as a raw material for polymer production in the form of an aqueous solution of acrylic acid. Moreover, it can be made highly purified acrylic acid by adding a refinement | purification process. The purification step can be performed by a known technique such as evaporation, distillation, extraction, membrane separation, crystallization, or a combination thereof.
以上の方法により、アクリル酸を製造することができる。かくして製造されたアクリル酸は、アクリル酸エステルなどのアクリル酸誘導体、ポリアクリル酸、ポリアクリル酸ナトリウムなどの親水性樹脂、吸水性樹脂などの合成原料として有用である。従って、本発明によるアクリル酸の製造方法は、アクリル酸誘導体や親水性樹脂の製造方法に取り入れることが当然可能である。 By the above method, acrylic acid can be produced. The acrylic acid thus produced is useful as a raw material for the synthesis of acrylic acid derivatives such as acrylic acid esters, hydrophilic resins such as polyacrylic acid and sodium polyacrylate, and water-absorbing resins. Therefore, the method for producing acrylic acid according to the present invention can naturally be incorporated into a method for producing an acrylic acid derivative or a hydrophilic resin.
３−ヒドロキシプロピオン酸は、公知の方法で入手可能であり、例えば国際公開第２００８／０２７７４２号に記載されている、Ｓｔｒｅｐｔｏｍｙｃｅｓ ｇｒｉｓｅｕｓ ＡＴＣＣ２１８９７由来ｂｅｔａ−ａｌａｎｉｎｅ ａｍｉｎｏｔｒａｎｓｆｅｒａｓｅ遺伝子導入大腸菌を用いた、グルコースを炭素源とした発酵により得ることができる。また、国際公開第２００１／０１６３４６号に記載されている、Ｋｌｅｂｓｉｅｌｌａ ｐｎｅｕｍｏｎｉａｅ由来グリセリン脱水酵素および大腸菌由来アルデヒド酸化酵素導入大腸菌を用いた、グリセリンを炭素源とした発酵によっても得ることができる。 3-Hydroxypropionic acid can be obtained by a known method. For example, a beta-alanine aminotransferase gene-transferred Escherichia coli derived from Streptomyces griseis ATCC21897 described in International Publication No. 2008/027742 is used as a carbon source. Can be obtained by fermentation. It can also be obtained by fermentation using glycerin as a carbon source using Klebsiella pneumoniae-derived glycerin dehydrase and Escherichia coli-derived aldehyde oxidase-introduced Escherichia coli described in International Publication No. 2001/016346.
３−ヒドロキシプロピオン酸の入手方法の例として上記公知文献を記載したが、本発明の方法を用いる限り、発酵に用いる細菌または組換え細菌は特に限定されず、３−ヒドロキシプロピオン酸生成能を有する生物を用いた発酵により入手した３−ヒドロキシプロピオン酸であれば本発明記載の方法で利用可能である。また、発酵以外にも原料とする糖類と生物とを接触させることで生成した３−ヒドロキシプロピオン酸でも本特許記載の方法でアクリル酸へ変換することができる。糖類と生物を接触させるとは、原料として利用する糖類の存在下で微生物又はその処理物を用いて反応を行うことをも包含する。該処理物としては、アセトン、トルエン等で処理した菌体、菌死体、凍結乾燥菌体、菌体破砕物、菌体を破砕した無細胞抽出物、これらから酵素を抽出した粗酵素液、精製酵素等が挙げられる。また、常法により担体に固定化した菌体、該処理物、酵素等を用いて反応を行うことにより入手した３−ヒドロキシプロピオン酸も用いることができる。 Although the said well-known literature was described as an example of the acquisition method of 3-hydroxypropionic acid, as long as the method of this invention is used, the bacteria or recombinant bacteria used for fermentation are not specifically limited, It has 3-hydroxypropionic acid production ability Any 3-hydroxypropionic acid obtained by fermentation using a living organism can be used in the method of the present invention. In addition to fermentation, 3-hydroxypropionic acid produced by bringing a saccharide as a raw material into contact with a living organism can be converted to acrylic acid by the method described in this patent. Contacting a saccharide with a living organism also includes performing a reaction using a microorganism or a processed product thereof in the presence of a saccharide used as a raw material. Examples of the treated products include cells treated with acetone, toluene, etc., fungus bodies, freeze-dried cells, disrupted cells, cell-free extracts obtained by disrupting cells, crude enzyme solutions obtained by extracting enzymes from these, purification An enzyme etc. are mentioned. In addition, 3-hydroxypropionic acid obtained by carrying out a reaction using the cells immobilized on a carrier by a conventional method, the treated product, an enzyme and the like can also be used.
本発明では、生物由来資源を用いて発酵により３−ヒドロキシプロピオン酸を得る具体的実施形態に係る方法において、固体、特に微細な植物の部分又は細胞及び／又は細胞断片、特に発酵の後に得られる３−ヒドロキシプロピオン酸及び微生物等を含む水性組成物から微生物や生物的材料等を分離するのが良い。前記分離は、固体を液状組成物から分離するための、当業者に公知の全ての方法により実施することができるが、好ましくは沈殿法、遠心分離法又は濾過法、最も好ましくは濾過法により分離するのがよい。 In the present invention, in a method according to a specific embodiment in which 3-hydroxypropionic acid is obtained by fermentation using biological resources, it is obtained after solid, especially fine plant parts or cells and / or cell fragments, especially after fermentation. It is preferable to separate microorganisms, biological materials, and the like from an aqueous composition containing 3-hydroxypropionic acid and microorganisms. Said separation can be carried out by all methods known to those skilled in the art for separating solids from liquid compositions, but preferably by precipitation, centrifugation or filtration, most preferably by filtration. It is good to do.
３−ヒドロキシプロピオン酸及び微生物等を含む水性組成物から微生物等を分離する処理においては、そこに含まれる微生物に処理を施すことなく行っても良いが、加熱処理して、そこに含まれる微生物を殺菌する処理工程を含んでも良い。前記水性組成物から微生物等を殺菌する処理は、微生物を分離する前、その間若しくは後に行うことができる。上記加熱処理の方法としては、３−ヒドロキシプロピオン酸及び微生物等を含む水性組成物を少なくとも６０秒間、好ましくは少なくとも１０分間、更に好ましくは少なくとも３０分間にわたり、少なくとも１００℃、特に好ましくは少なくとも１１０℃、更に好ましくは少なくとも１２０℃の温度で加熱することによって実施するのが好ましく、当該加熱処理は、当業者に公知の装置（例えばオートクレーブ）において実施するのが好ましい。高エネルギー照射（例えば紫外線照射）により微生物を殺菌してもよいが、加熱による微生物の殺菌が特に好適である。 In the treatment for separating microorganisms and the like from the aqueous composition containing 3-hydroxypropionic acid and microorganisms, the microorganisms contained therein may be performed without being treated, but the microorganisms contained therein are subjected to heat treatment. It may include a processing step of sterilizing. The treatment for sterilizing microorganisms and the like from the aqueous composition can be performed before, during or after separating the microorganisms. As the heat treatment method, an aqueous composition containing 3-hydroxypropionic acid, microorganisms and the like is used for at least 60 seconds, preferably at least 10 minutes, more preferably at least 30 minutes, at least 100 ° C., particularly preferably at least 110 ° C. More preferably, it is preferably carried out by heating at a temperature of at least 120 ° C., and the heat treatment is preferably carried out in an apparatus known to those skilled in the art (for example, an autoclave). Although microorganisms may be sterilized by high energy irradiation (for example, ultraviolet irradiation), sterilization of microorganisms by heating is particularly preferable.
３−ヒドロキシプロピオン酸を含む水性組成物から、さらに３−ヒドロキシプロピオン酸を回収する方法としては公知の技術が使用できる。例えば、蒸留、蒸発、抽出、膜分離、晶析、イオン交換、電気透析等が挙げられ、これらを組み合わせても良い。さらに具体的には、発酵により得られた粗製ヒドロキシプロピオン酸を、カルシウム塩を用いて沈殿させて３−ヒドロキシプロピオン酸のカルシウム塩として回収し、その後、硫酸等の酸と反応させて３−ヒドロキシプロピオン酸を精製する方法、または発酵により得たアンモニウム型の３−ヒドロキシプロピオン酸を電気透析または陽イオン交換法によって３−ヒドロキシプロピオン酸に化学変換させて精製する方法等が利用できる。また、発酵により得られたアンモニウム型の３−ヒドロキシプロピオン酸に、水に不混和性のアミン溶媒を添加し加熱することで、アンモニアを除去して３−ヒドロキシプロピオン酸のアミン溶液を得ることができる。そこに水を加えて加熱することで、３−ヒドロキシプロピオン酸の水溶液を得ることができる。このようにして発酵液より、３−ヒドロキシプロピオン酸溶液を得ることができる。この３−ヒドロキシプロピオン酸溶液を、本発明の条件にて取り扱うまたは保管することによって、３−ヒドロキシプロピオン酸を誘導体化するに十分な品質を保持することができる。 As a method for further recovering 3-hydroxypropionic acid from an aqueous composition containing 3-hydroxypropionic acid, a known technique can be used. For example, distillation, evaporation, extraction, membrane separation, crystallization, ion exchange, electrodialysis and the like may be mentioned, and these may be combined. More specifically, crude hydroxypropionic acid obtained by fermentation is precipitated using a calcium salt and recovered as a calcium salt of 3-hydroxypropionic acid, and then reacted with an acid such as sulfuric acid to give 3-hydroxy A method of purifying propionic acid or a method of chemically converting ammonium-type 3-hydroxypropionic acid obtained by fermentation into 3-hydroxypropionic acid by electrodialysis or cation exchange method can be used. In addition, by adding an amine solvent immiscible with water and heating the ammonium-type 3-hydroxypropionic acid obtained by fermentation, ammonia can be removed to obtain an amine solution of 3-hydroxypropionic acid. it can. An aqueous solution of 3-hydroxypropionic acid can be obtained by adding water thereto and heating. In this way, a 3-hydroxypropionic acid solution can be obtained from the fermentation broth. By treating or storing this 3-hydroxypropionic acid solution under the conditions of the present invention, a quality sufficient to derivatize 3-hydroxypropionic acid can be maintained.
以下、実施例を挙げて本発明をより具体的に説明するが、本発明はもとより下記の実施例により制限を受けるものではなく、前・後記の趣旨に適合し得る範囲で適当に変更を加えて実施することも可能であり、それらはいずれも本発明の技術的範囲に包含される。
なお、以下ことわりのない場合、「％」は「質量％」を、「部」は「質量部」をそれぞれ示すものとする。
Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples, and appropriate modifications are made within a range that can meet the purpose described above and below. Any of these can be carried out and are included in the technical scope of the present invention.
Unless otherwise specified, “%” indicates “mass%” and “part” indicates “mass part”.
（調製例１）
３−ヒドロキシプロピオン酸（３ＨＰ）を含む組成物の取得
Ｋｌｅｂｓｉｅｌｌａ ｐｎｅｕｍｏｎｉａｅ ＡＴＣＣ２５９５５株のゲノムＤＮＡをテンプテレ−トとしてグリセロールデヒドラターゼ遺伝子（ＧＤ遺伝子）およびグリセロールデヒドラターゼ再活性化因子（ＧＤＲ遺伝子）を含む領域を、下記の２つのプライマーを用いてＰＣＲで増幅し、増幅断片の末端を制限酵素ＮｄｅＩ、ＢｇｌＩＩで切断し、電気泳動によって切断断片を回収した。なお、ＧＤ遺伝子およびＧＤＲ遺伝子配列を増幅する以下のプライマーはＧｅｎＢａｎｋ Ａｃｃｅｓｓｉｏｎ ｎｕｍｂｅｒ：ＮＣ＿００９６４８記載のＤＮＡ配列を元に設計した。
フォワードプライマー：
５’−ＧＣＧＣＧＣＣＡＴＡＴＧＴＴＡＡＴＴＣＧＣＣＴＧＡＣＣＧＧＣＣ−３’
リバースプライマー：
５’−ＧＣＧＣＧＣＡＧＡＴＣＴＴＣＡＧＴＴＴＣＴＣＴＣＡＣＴＴＡＡＣＧ−３’
ｐＡＣＹＣＤｕｅｔ−１プラスミド（タカラバイオ社）をテンプレートにして下記の２つのプライマーでベクター配列を増幅し、ｐＡＣＹＣＤｕｅｔ−１プラスミドのＴ７プロモーターの後ろにＮｄｅＩサイトおよびＢｇｌ ＩＩサイトを持ったＤＮＡ断片を増幅した。
フォワードプライマー：
５’−ＧＡＡＧＧＡＧＡＴＡＴＡＣＡＴＡＴＧＧＣＧＣＧＣ−３’
リバースプライマー：
５’−ＣＣＧＡＴＡＴＣＣＡＡＴＴＧＡＧＡＴＣＴＧＣＧＣＧＣ−３’
増幅断片を制限酵素ＢｇｌＩＩとＮｄｅＩで切断し、電気泳動によって切断断片を分離して回収した。この２つのＤＮＡ断片をライゲーションし、大腸菌ＴＯＰ１０コンピテントセル（インビトロジェン社）に導入し、クロラムフェニコール含有プレートに広げて培養しところ、クロラムフェニコール耐性大腸菌を得ることができた。クロラムフェニコール耐性大腸菌からプラスミドＤＮＡを抽出し、制限酵素により分子量の確認を行ったところ、目的とするＧＤ遺伝子およびＧＤＲ遺伝子がｐＡＣＹＣＤｕｅｔ−１プラスミドに挿入されていることが確認できた。構築した組換えプラスミドをＧＤ−ＧＤＲ／ｐＡＣＹＣＤｕｅｔ−１と命名し、以降の実験に用いた。
(Preparation Example 1)
Obtaining a composition containing 3-hydroxypropionic acid (3HP) A region containing a glycerol dehydratase gene (GD gene) and a glycerol dehydratase reactivating factor (GDR gene) using the genomic DNA of Klebsiella pneumoniae ATCC 25955 as a template. The ends of the amplified fragment were cleaved with restriction enzymes NdeI and BglII, and the cleaved fragment was recovered by electrophoresis. The following primers for amplifying the GD gene and GDR gene sequences were designed based on the DNA sequence described in GenBank Accession number: NC_009648.
Forward primer:
5′-GCCGCGCCATATGTTAATTCGCGCTGACCGGCC-3 ′
Reverse primer:
5′-GCGCGCAGAATTCTCAGTTTCTCTCACTTAACG-3 ′
A vector sequence was amplified with the following two primers using pACYCDuet-1 plasmid (Takara Bio Inc.) as a template, and a DNA fragment having an NdeI site and a BglII site behind the T7 promoter of the pACYCDuet-1 plasmid was amplified.
Forward primer:
5'-GAAGGAGATATACACATGGGCGC-3 '
Reverse primer:
5′-CCGATATCCAATTGAGATCTGGCGCC-3 ′
The amplified fragment was cleaved with restriction enzymes BglII and NdeI, and the cleaved fragment was separated and recovered by electrophoresis. These two DNA fragments were ligated, introduced into E. coli TOP10 competent cell (Invitrogen), spread on a chloramphenicol-containing plate and cultured, and chloramphenicol resistant E. coli could be obtained. When plasmid DNA was extracted from chloramphenicol resistant Escherichia coli and molecular weight was confirmed with restriction enzymes, it was confirmed that the target GD gene and GDR gene were inserted into the pACYCDuet-1 plasmid. The constructed recombinant plasmid was named GD-GDR / pACYCDuet-1 and used for the subsequent experiments.
大腸菌Ｋ−１２ Ｗ３１１０株のゲノムＤＮＡをテンプテレ−トとしてγ−ｇｌｕｔａｍｙｌ−γ−ａｍｉｎｏｂｕｔｙｒａｌｄｅｈｙｄｅ ｄｅｈｙｄｒｏｇｅｎａｓｅ遺伝子（ａｌｄＨ遺伝子）を下記の２つのプライマーを用いてＰＣＲ法で増幅し、増幅断片の末端を制限酵素ＮｄｅＩ、ＢｇｌＩＩで切断し、電気泳動によって切断断片を回収した。なお、以下プライマーはＧｅｎＢａｎｋ Ａｃｃｅｓｓｉｏｎ ｎｕｍｂｅｒ：ＡＢ２００３１９記載のＤＮＡ配列を元に設計した。
フォワードプライマー：
５’−ＧＧＧＧＧＧＣＣＡＴＡＴＧＡＡＴＴＴＴＣＡＴＣＡＴＣＴＧＧＣＴＴＡＣＴＧ−３’
リバースプライマー：
５’−ＣＣＣＣＡＧＡＴＣＴＴＣＡＧＧＣＣＴＣＣＡＧＧＣＴＴＡＴＣＣＡＧＡＴＧ−３’
ｐＵＣ１８プラスミドをテンプレートにして下記の２つのプライマーでベクター配列を増幅し、ｐＵＣ１８プラスミドのｌａｃプロモーターの後ろにＮｄｅＩサイトを持ち、ｌａｃＺ遺伝子の終始コドンの位置にＢａｍＨＩサイトを持ったＤＮＡ断片を増幅した。
フォワードプライマー：
５’−ＣＣＣＣＣＣＣＡＴＡＴＧＴＧＴＴＴＣＣＴＧＴＧＴＧＡＡＡＴＴＧＴＴＡＴＣＣＧＣＴＣＡＣＡＡＴＴＣＣＡＣＡＣＡＡＴＡＴＡＣＧＡＧＣＣ−３’
リバースプライマー：
５’−ＣＣＣＣＧＧＡＴＣＣＴＴＡＧＴＴＡＡＧＣＣＡＧＣＣＣＣＧＡＣＡＣＣＣＧＣＣＡＡＣＡＣＣ−３’
増幅断片を制限酵素ＢａｍＨＩとＮｄｅＩで切断し、電気泳動によって切断断片を分離して回収した。この２つのＤＮＡ断片をライゲーションし、大腸菌ＴＯＰ１０コンピテントセルに導入し、アンピシリン含有プレートに広げて培養した。得られた形質転換体からプラスミドを抽出し、制限酵素処理により分子量の確認をしたところ、目的どおり、ａｌｄＨがｐＵＣ１８プラスミドに挿入されていることを確認した。構築した組換えプラスミドをａｌｄＨ／ｐＵＣ１８と命名し、以降の実験で使用した。
構築したＧＤ−ＧＤＲ／ｐＡＣＹＣＤｕｅｔ−１およびａｌｄＨ／ｐＵＣ１８をＥｓｃｈｅｒｉｃｈｉａ ｃｏｌｉ ＢＬ２１（ＤＥ３） ｃｏｍｐｅｔｅｎｔ ｃｅｌｌ（Ｍｅｒｃｋ社）のプロトコールに従って、ヒートショック法により導入し、Ｅ．ｃｏｌｉ（ＧＤ−ＧＤＲ／ｐＡＣＹＣＤｕｅｔ−１、ａｌｄＨ／ｐＵＣ１８）を作出した。
The genomic DNA of Escherichia coli K-12 W3110 strain was used as a template to amplify the γ-glutamyl-γ-aminobutyraldehyde dehydrogenase gene (aldH gene) by the PCR method using the following two primers, and the ends of the amplified fragments were restricted with the restriction enzyme NdeI And digested with BglII, and the cleaved fragments were recovered by electrophoresis. The primers below were designed based on the DNA sequence described in GenBank Accession number: AB2003319.
Forward primer:
5′-GGGGGGCCATATGAATTTTCATCATCTGGCTTACTG-3 ′
Reverse primer:
5′-CCCCAGATCTTCAGGCCTCCAGGCTTATTCCAGATG-3 ′
The vector sequence was amplified with the following two primers using the pUC18 plasmid as a template, and a DNA fragment having an NdeI site behind the lac promoter of the pUC18 plasmid and a BamHI site at the position of the start codon of the lacZ gene was amplified.
Forward primer:
5'-CCCCCCCCATATGTTTTCCTGTGTGAAATTGTTTCCGCTCCACAATTCCACCAAATATACGAGCC-3 '
Reverse primer:
5'-CCCCGGATCCCTTAGTTTAAGCCAGCCCCGACACCGCCCAAACACC-3 '
The amplified fragment was cleaved with restriction enzymes BamHI and NdeI, and the cleaved fragment was separated and recovered by electrophoresis. These two DNA fragments were ligated, introduced into E. coli TOP10 competent cells, spread on ampicillin-containing plates and cultured. When a plasmid was extracted from the obtained transformant and molecular weight was confirmed by restriction enzyme treatment, it was confirmed that aldH was inserted into the pUC18 plasmid as intended. The constructed recombinant plasmid was named aldH / pUC18 and used in the subsequent experiments.
The constructed GD-GDR / pACYCDuet-1 and aldH / pUC18 were introduced by the heat shock method according to the protocol of Escherichia coli BL21 (DE3) competent cell (Merck). E. coli (GD-GDR / pACYCDuet-1, aldH / pUC18) was generated.
Ｅ．ｃｏｌｉ（ＧＤ−ＧＤＲ／ｐＡＣＹＣＤｕｅｔ−１、ａｌｄＨ／ｐＵＣ１８）を、アンピシリン１００ｐｐｍ、クロラムフェニコール５０ｐｐｍ添加ＬＢ液体培地５ｍＬ（ＬＢ培地１Ｌあたりの組成：トリプトン１０ｇ、酵母エキス５ｇ、ＮａＣｌ１０ｇ）で３７℃、１６時間、振盪培養し、前培養液を得た。次に前培養液５ｍＬを、アンピシリン１００ｐｐｍ、クロラムフェニコール５０ｐｐｍ、添加ＮＳ液体培地１Ｌに植菌し、３７℃、攪拌速度７２５ｒｐｍ、通気量１Ｌ／ｍｉｎ、で通気攪拌培養を行った。なお、ＮＳ液体培地の組成は、グリセリン４０ｇ／Ｌ、硫酸アンモニウム１０ｇ／Ｌ、リン酸二水素カリウム２ｇ／Ｌ、リン酸水素二カリウム６ｇ／Ｌ、硫酸マグネシウム７水和物１ｇ／Ｌ、酵母エキス４０ｇ／Ｌである。また、培養には、バイオット製ジャーファーメンター：ＢＭＪ−０２ＮＰ２を使用し、培養中はアンモニア水を用いて培養液中のｐＨを７にコントロールした。培養８時間後に１Ｍ ＩＰＴＧ溶液を１ｍＬ、８ｍＭアデノシルコバラミン溶液を１ｍＬ添加し、培養途中にグリセリンが枯渇しないように適時グリセリンを添加しながら１００時間培養を行った。得られた培養液を遠心分離にかけ、培養液上清を回収した。以下記載の高速液体クロマトグラフィーを用いた分析方法で培養液上清中の生成物の確認を行ったところ、生成物である３−ヒドロキシプロピオン酸のピークを７．９分の位置に確認することができ、培養液中の３−ヒドロキシプロピオン酸の濃度は２質量％であった。 E. coli (GD-GDR / pACYCDuet-1, aldH / pUC18) at 37 ° C. in 5 mL of LB liquid medium containing 100 ppm of ampicillin and 50 ppm of chloramphenicol (composition per liter of LB medium: 10 g of tryptone, 5 g of yeast extract, 10 g of NaCl), The preculture was obtained by shaking culture for 16 hours. Next, 5 mL of the preculture solution was inoculated into 1 L of ampicillin 100 ppm, chloramphenicol 50 ppm, and added NS liquid medium, and aerated and stirred culture was performed at 37 ° C., a stirring speed of 725 rpm, and an aeration rate of 1 L / min. The composition of the NS liquid medium is glycerin 40 g / L, ammonium sulfate 10 g / L, potassium dihydrogen phosphate 2 g / L, dipotassium hydrogen phosphate 6 g / L, magnesium sulfate heptahydrate 1 g / L, yeast extract 40 g. / L. In addition, jar fermenter manufactured by Biot: BMJ-02NP2 was used for the culture, and the pH in the culture solution was controlled to 7 using aqueous ammonia during the culture. After 8 hours of culture, 1 mL of 1M IPTG solution and 1 mL of 8 mM adenosylcobalamin solution were added, and culture was performed for 100 hours while adding glycerin in a timely manner so that glycerin was not depleted during the culture. The obtained culture broth was centrifuged and the culture supernatant was collected. When the product in the culture supernatant is confirmed by the analysis method using high performance liquid chromatography described below, the peak of 3-hydroxypropionic acid as the product should be confirmed at a position of 7.9 minutes. The concentration of 3-hydroxypropionic acid in the culture solution was 2% by mass.
高速液体クロマトグラフィーでの分析条件：
使用カラム： ＹＭＣ−ｐＡＣＫ ＦＡ（ＹＭＣ社）
流量：１ｍＬ／ｍｉｎ
インジェクション量：１０μＬ
溶離液：メタノール／アセトニトリル／Ｈ２Ｏ＝４０／５／５５（Ｖ／Ｖ／Ｖ）
内部標準：２−Ｈｙｄｒｏｘｙ−２−ｍｅｔｈｙｌ−ｎ−ｂｕｔｙｒｉｃ ａｃｉｄ
検出：ＵＶ ４００ｎｍ
培養上清１００μＬに内部標準液２００μＬを加えた。ヒドロキシカルボン酸ラベル化試薬（ＹＭＣ社）の試薬Ａ液２００μＬ、試薬Ｂ液２００μＬを加え、よく混合した後、６０℃、２０分間処理した。ヒドロキシカルボン酸ラベル化試薬（ＹＭＣ社）の試薬Ｃ液２００μＬを添加し、よく混合した。６０℃、１５分間処理後、室温まで冷えたら０．４５ｍｍフィルターに通し、ＬＣ分析サンプルとして供した。
Analytical conditions for high performance liquid chromatography:
Column used: YMC-pACK FA (YMC)
Flow rate: 1 mL / min
Injection volume: 10μL
Eluent: methanol / acetonitrile / H 2 O = 40/5/55 (V / V / V)
Internal standard: 2-Hydroxy-2-methyl-n-butyric acid
Detection: UV 400nm
200 μL of an internal standard solution was added to 100 μL of the culture supernatant. 200 μL of reagent A solution and 200 μL of reagent B solution of a hydroxycarboxylic acid labeling reagent (YMC) were added and mixed well, followed by treatment at 60 ° C. for 20 minutes. 200 μL of reagent C solution of a hydroxycarboxylic acid labeling reagent (YMC) was added and mixed well. After being treated at 60 ° C. for 15 minutes and then cooled to room temperature, it was passed through a 0.45 mm filter and used as an LC analysis sample.
菌体を除去した２質量％の３−ヒドロキシプロピオン酸含有培養液からＷＯ２００２／０９０３１２記載の方法で、３ＨＰを１２質量％含む水溶液を得た。またこの水溶液中には、発酵副生物である酢酸が７．２質量％含まれていた。 An aqueous solution containing 12% by mass of 3HP was obtained from the 2% by mass of 3-hydroxypropionic acid-containing culture solution from which the cells had been removed, by the method described in WO2002 / 090312. The aqueous solution contained 7.2% by mass of acetic acid as a fermentation by-product.
（実施例１）
調製例１で得られた３ＨＰ水溶液を、薄膜式蒸発器を用いて濃縮を行った。圧力を２０ｍｍＨｇ、ジャケット温度を５０℃として、軽沸分を留去した。得られたボトム液をさらに薄膜蒸発器にかけ、圧力２ｍｍＨｇ、ジャケット温度を１００℃として、３ＨＰを含む留分を得た。この留分を３ＨＰ溶液とした。この３ＨＰ溶液中の３ＨＰ濃度は８８．０質量％であった。この溶液を、３５℃、５０℃にて２４時間保管した。保管後の３ＨＰ濃度は、３５℃保管の場合で８１．３質量％、５０℃保管の場合で６９．１質量％であった。
Example 1
The 3HP aqueous solution obtained in Preparation Example 1 was concentrated using a thin film evaporator. The light boiling point was distilled off at a pressure of 20 mmHg and a jacket temperature of 50 ° C. The obtained bottom liquid was further applied to a thin film evaporator to obtain a fraction containing 3HP at a pressure of 2 mmHg and a jacket temperature of 100 ° C. This fraction was used as a 3HP solution. The 3HP concentration in the 3HP solution was 88.0% by mass. This solution was stored at 35 ° C. and 50 ° C. for 24 hours. The 3HP concentration after storage was 81.3% by mass when stored at 35 ° C. and 69.1% by mass when stored at 50 ° C.
（比較例１）
実施例１で得られた、８８．０質量％の３ＨＰ溶液を６５℃で２４時間保管した。保管後の３ＨＰ濃度は３０．７質量％であった。
(Comparative Example 1)
The 88.0 mass% 3HP solution obtained in Example 1 was stored at 65 ° C. for 24 hours. The 3HP concentration after storage was 30.7% by mass.
（比較例２）
調製例１で得られた３ＨＰ水溶液を、薄膜式蒸発器を用いて濃縮を行った。圧力を１５ｍｍＨｇ、ジャケット温度を５０℃として、軽沸分を留去した。得られたボトム液をさらに薄膜蒸発器にかけ、圧力２ｍｍＨｇ、ジャケット温度を１００℃として、３ＨＰを含む留分を得た。この留分を３ＨＰ溶液とした。この３ＨＰ溶液中の３ＨＰ濃度は９５．０質量％であった。この溶液を、５０℃にて２４時間保管した。保管後の３ＨＰ濃度は、４３．５質量％であった。
(Comparative Example 2)
The 3HP aqueous solution obtained in Preparation Example 1 was concentrated using a thin film evaporator. The light boiling component was distilled off at a pressure of 15 mmHg and a jacket temperature of 50 ° C. The obtained bottom liquid was further applied to a thin film evaporator to obtain a fraction containing 3HP at a pressure of 2 mmHg and a jacket temperature of 100 ° C. This fraction was used as a 3HP solution. The 3HP concentration in this 3HP solution was 95.0% by mass. This solution was stored at 50 ° C. for 24 hours. The 3HP concentration after storage was 43.5% by mass.
（実施例２）
実施例１で得られた８８．０質量％の３ＨＰ溶液に、水を添加して３ＨＰが４９．３質量％になるように調製した。この３ＨＰ溶液中の酢酸濃度は、５．４質量％（３ＨＰに対して１６．４ｍｏｌ％）であった。この溶液を３５℃で２４時間保管した。保管後の３ＨＰ濃度は、４８．３質量％であった。
(Example 2)
Water was added to the 88.0 mass% 3HP solution obtained in Example 1 to prepare 3HP at 49.3 mass%. The acetic acid concentration in this 3HP solution was 5.4% by mass (16.4 mol% with respect to 3HP). This solution was stored at 35 ° C. for 24 hours. The 3HP concentration after storage was 48.3 mass%.
（実施例３）
調製例１で得られた、１２質量％の３ＨＰ水溶液を薄膜蒸発器で濃縮を行った。圧力３０ｍｍＨｇ、ジャケット温度４０℃として、軽沸分を除去した。得られたボトム液をさらに薄膜蒸発器にかけ、圧力２ｍｍＨｇ、ジャケット温度を１００℃として、３ＨＰを含む留分を得た。その留分に水を添加して３ＨＰが４９．３質量％になるように調製し３ＨＰ溶液とした。この溶液中の酢酸濃度は、１７．７質量％（３ＨＰに対して５３．９ｍｏｌ％）であった。この溶液を３５℃で２４時間保管した。保管後の３ＨＰ濃度は、４５．４質量％であった。
(Example 3)
The 12 mass% 3HP aqueous solution obtained in Preparation Example 1 was concentrated using a thin film evaporator. Light boiling was removed at a pressure of 30 mmHg and a jacket temperature of 40 ° C. The obtained bottom liquid was further applied to a thin film evaporator to obtain a fraction containing 3HP at a pressure of 2 mmHg and a jacket temperature of 100 ° C. Water was added to the fraction to prepare a 3HP solution by adjusting 3HP to 49.3 mass%. The acetic acid concentration in this solution was 17.7% by mass (53.9 mol% with respect to 3HP). This solution was stored at 35 ° C. for 24 hours. The 3HP concentration after storage was 45.4% by mass.
（実施例４）
調製例１において、培養液のｐＨ調整をアンモニア水の代わりに水酸化カルシウムを用いて実施した。培養終了後、培養液に、使用した水酸化カルシウムに対して９８モル％相当の硫酸水溶液を滴下し、３０℃で２時間撹拌した。得られた液から濾過により、菌体と生成した硫酸カルシウムを除去した。濾液を１００℃で２時間加熱することにより、タンパク質の変性物を析出させ、これを濾過により除去した。得られた濾液を、薄膜蒸発器にて濃縮した。圧力を２０ｍｍＨｇ、ジャケット温度を５０℃として、軽沸分を留去した（薄膜蒸発１回目）。得られたボトム液をさらに薄膜蒸発器にかけ、圧力２ｍｍＨｇ、ジャケット温度を１００℃として、３ＨＰを含む留分を得た（薄膜蒸発２回目）。得られた留分に水を添加し、３ＨＰが６９．０質量％になるように調製し３ＨＰ溶液とした。この溶液中のリン酸イオン、アンモニウムイオン、マグネシウムイオン、カルシウムイオン、ナトリウムイオン、カリウムイオンをイオンクロマトグラフィーにて分析した（表１）。この溶液を３５℃にて２４時間保管した。保管後の３ＨＰ濃度は６５．９％質量であった。
Example 4
In Preparation Example 1, the pH of the culture solution was adjusted using calcium hydroxide instead of ammonia water. After completion of the culture, an aqueous sulfuric acid solution equivalent to 98 mol% with respect to the used calcium hydroxide was added dropwise to the culture solution, followed by stirring at 30 ° C for 2 hours. The bacterial cells and produced calcium sulfate were removed from the obtained liquid by filtration. The filtrate was heated at 100 ° C. for 2 hours to precipitate a protein denatured product, which was removed by filtration. The resulting filtrate was concentrated in a thin film evaporator. The pressure was 20 mmHg, the jacket temperature was 50 ° C., and light boiling components were distilled off (first thin film evaporation). The obtained bottom liquid was further applied to a thin film evaporator to obtain a fraction containing 3HP at a pressure of 2 mmHg and a jacket temperature of 100 ° C. (second thin film evaporation). Water was added to the obtained fraction to prepare 3HP solution by adjusting 3HP to 69.0% by mass. Phosphate ion, ammonium ion, magnesium ion, calcium ion, sodium ion and potassium ion in this solution were analyzed by ion chromatography (Table 1). This solution was stored at 35 ° C. for 24 hours. The 3HP concentration after storage was 65.9% by mass.
（実施例５）
実施例４において、薄膜蒸発１回目で得られたボトム液に水を添加した後、陽イオン交換樹脂アンバーリスト１５（オルガノ社製）を添加し、３０℃で２時間撹拌し、液中のイオン成分を吸着させた。陽イオン交換樹脂および析出物を除去後、３ＨＰが６９．０質量％になるように調製し３ＨＰ溶液とした。この溶液中のリン酸イオン、アンモニウムイオン、マグネシウムイオン、カルシウムイオン、ナトリウムイオン、カリウムイオンをイオンクロマトグラフィーにて分析した（表１）。この溶液を３５℃にて２４時間保管した。保管後の３ＨＰ濃度は５８．１質量％であった。
(Example 5)
In Example 4, after adding water to the bottom liquid obtained in the first thin film evaporation, cation exchange resin Amberlyst 15 (manufactured by Organo) was added, and the mixture was stirred at 30 ° C. for 2 hours. The components were adsorbed. After removing the cation exchange resin and the precipitate, 3HP was prepared to be 69.0% by mass to obtain a 3HP solution. Phosphate ion, ammonium ion, magnesium ion, calcium ion, sodium ion and potassium ion in this solution were analyzed by ion chromatography (Table 1). This solution was stored at 35 ° C. for 24 hours. The 3HP concentration after storage was 58.1% by mass.
（実施例６）
実施例１において３５℃で保管して得られた３ＨＰ溶液に、水を添加して３ＨＰ濃度が６０質量％になるように原料組成物を調整した。ＮＭＲにて、３ＨＰと３ＨＰのオリゴマーを分析したところ、３ＨＰに対して、３ＨＰオリゴマーは８質量％含まれていた。上記３ＨＰ水溶液にメトキノンを１００質量ｐｐｍになるように添加した。
内径１０ｍｍの反応管に、固体触媒としてγ−アルミナを充填し、その上に蒸発層としてディクソンパッキンを充填した。反応管を電気炉にて３００℃に加熱し、上記原料組成物を毎時２．９ｇの速度で反応管の上部に供給した。同時に、毎時２０Ｌの速度で窒素ガスを流した。８時間継続して脱水反応を実施した。
反応管の下部から抜き出した反応ガスを、冷却捕集し反応液を得た。得られた反応液を液体クロマトグラフィーで分析したところ、３ＨＰおよび３ＨＰオリゴマーの転化率は９５％、３ＨＰと３ＨＰオリゴマーの合計に対するアクリル酸の収率は９０モル％であった。
(Example 6)
Water was added to the 3HP solution obtained by storage at 35 ° C. in Example 1 to adjust the raw material composition so that the 3HP concentration was 60% by mass. When 3HP and 3HP oligomers were analyzed by NMR, 8 mass% of 3HP oligomers were contained with respect to 3HP. Metoquinone was added to the 3HP aqueous solution so as to be 100 ppm by mass.
A reaction tube having an inner diameter of 10 mm was filled with γ-alumina as a solid catalyst, and Dixon packing was filled thereon as an evaporation layer. The reaction tube was heated to 300 ° C. in an electric furnace, and the raw material composition was supplied to the upper portion of the reaction tube at a rate of 2.9 g per hour. At the same time, nitrogen gas was flowed at a rate of 20 L / hour. The dehydration reaction was carried out continuously for 8 hours.
The reaction gas extracted from the lower part of the reaction tube was cooled and collected to obtain a reaction solution. When the obtained reaction liquid was analyzed by liquid chromatography, the conversion rate of 3HP and 3HP oligomers was 95%, and the yield of acrylic acid based on the total of 3HP and 3HP oligomers was 90 mol%.
（比較例３）
比較例２で保管された３ＨＰ溶液を、実施例６の原料組成物と３ＨＰとオリゴマー（３ＨＰ換算）の合計濃度が同じになるように調製した。３ＨＰ濃度は２９．８質量％、３ＨＰのオリゴマーは３１．７質量％であり、３ＨＰに対して、３ＨＰのオリゴマーは１０７質量％含まれていた。この原料組成物を、実施例６と同じ条件で脱水反応に用いた。３ＨＰおよび３ＨＰオリゴマーの転化率は８８％、３ＨＰと３ＨＰオリゴマーの合計に対するアクリル酸の収率は７２モル％であった。
(Comparative Example 3)
The 3HP solution stored in Comparative Example 2 was prepared so that the total concentration of the raw material composition of Example 6, 3HP, and oligomer (3HP equivalent) was the same. The 3HP concentration was 29.8% by mass, the 3HP oligomer was 31.7% by mass, and the 3HP oligomer was 107% by mass relative to 3HP. This raw material composition was used in the dehydration reaction under the same conditions as in Example 6. The conversion rate of 3HP and 3HP oligomer was 88%, and the yield of acrylic acid based on the sum of 3HP and 3HP oligomer was 72 mol%.
本発明は、発酵により生成した３−ヒドロキシプロピオン酸を含む溶液を安定に取扱いまたは保管することができ、さらにこの３−ヒドロキシプロピオン酸溶液を原料として高品質のアクリル酸を高収率で安定的かつ連続的に製造することを可能にする。リサイクル可能な生物由来資源（例えばバイオマス）から入手または調製された３−ヒドロキシプロピオン酸を使用するため、地球温暖化対策に多大の貢献をなすものである。 The present invention can stably handle or store a solution containing 3-hydroxypropionic acid produced by fermentation, and can stably produce high-quality acrylic acid in a high yield using this 3-hydroxypropionic acid solution as a raw material. And it is possible to manufacture continuously. Since 3-hydroxypropionic acid obtained or prepared from a recyclable biological resource (for example, biomass) is used, it greatly contributes to global warming countermeasures.
Claims (6)
該方法は、溶液中の水の含有量を１０〜９０質量％とし、溶液中にアミンおよび／またはアンモニウム塩の形で存在する窒素の量が、３−ヒドロキシプロピオン酸に対して、１７質量ｐｐｍ以上、５００質量ｐｐｍ以下である溶液を５〜５０℃の範囲で保管することを特徴とする３−ヒドロキシプロピオン酸溶液の保管の方法。 3-hydroxy propionic acid produced by fermentation, a method of holding tubes of a solution containing a concentration of 10 to 90 wt%,
In the method, the content of water in the solution is 10 to 90% by mass, and the amount of nitrogen present in the solution in the form of amine and / or ammonium salt is 17 mass ppm with respect to 3-hydroxypropionic acid. above, the method of holding tubes 3-hydroxypropionic acid solution characterized in that holding tube a solution of 500 ppm by mass or less in the range of 5 to 50 ° C..
該製造方法は、発酵により生成した３−ヒドロキシプロピオン酸を１０〜９０質量％の濃度で含む溶液を保管する工程と
該保管工程後の３−ヒドロキシプロピオン酸溶液を脱水する工程とを有し、
該保管工程は、溶液中の水の含有量が１０〜９０質量％であり、溶液中にアミンおよび／またはアンモニウム塩の形で存在する窒素の量が、３−ヒドロキシプロピオン酸に対して、１７質量ｐｐｍ以上、５００質量ｐｐｍ以下である溶液を５〜５０℃の範囲で保管することを特徴とするアクリル酸の製造方法。
A method for producing acrylic acid, comprising:
The manufacturing method, a solution containing 3-hydroxypropionic acid produced by fermentation at a concentration of 10 to 90% by weight comprising the steps of holding tube
Dehydrating the 3-hydroxypropionic acid solution after the storage step,
In the storage step, the content of water in the solution is 10 to 90% by mass, and the amount of nitrogen present in the solution in the form of amine and / or ammonium salt is based on 3-hydroxypropionic acid, 17 mass ppm or more, the production method of acrylic acid, characterized by holding tube in the range solution of 5 to 50 ° C. is 500 mass ppm or less.
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