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    Process for the fermentative preparation of L-amino acids from .alpha.-keto carboxylic acids
    1.
    发明授权
    Process for the fermentative preparation of L-amino acids from .alpha.-keto carboxylic acids 失效
    来自（ALPHA） - 羧基羧酸的L-氨基酸的发酵制备方法

    公开(公告)号：US5053328A

    公开(公告)日：1991-10-01

    申请号：US908777

    申请日：1986-09-18

    申请人： Bernhard Muetze ,  Christian Wandrey ,  Wolfgang Leuchtenberger ,  Toshihisa Ohshima

    发明人： Bernhard Muetze ,  Christian Wandrey ,  Wolfgang Leuchtenberger ,  Toshihisa Ohshima

    IPC分类号： C12N9/06 ,  C12P13/04 ,  C12P13/06 ,  C12R1/07

    CPC分类号： C12P13/06 ,  C12P13/04 ,  Y10S435/832 ,  Y10S435/833 ,  Y10S435/834 ,  Y10S435/835 ,  Y10S435/836 ,  Y10S435/837 ,  Y10S435/838 ,  Y10S435/839

    摘要： The preparation of an L-amino acid, particularly valine, leucine, isoleucine, alanine and phenylalanine, from the corresponding .alpha.-keto carboxylic acid by bacterial fermentation in the presence of ammonium ions is carried out with the aid of thermophilic Bacillus strains at temperatures above 45.degree. C., in particular above 60.degree. C. Bacillus strains DSM 406, 452, 461, 42, 463, 465 and 466 are particularly suitable for this purpose. The greater solubility of the amino acid at the elevated fermentation temperature permits the separation out of the amino acid from the reaction mixture simply by cooling, whereafter the depleted reaction mixture can be pumped back into the fermenter. Especially favorable yields are achieved by supplying oxygen to the fermenter to an amount of less than about 20% dissolved oxygen.

    摘要翻译： 在铵离子存在下通过细菌发酵从相应的α-酮羧酸制备L-氨基酸，特别是缬氨酸，亮氨酸，异亮氨酸，丙氨酸和苯丙氨酸，借助于嗜热芽孢杆菌菌株，在温度高于 45℃，特别是高于60℃。芽孢杆菌菌株DSM 406,452,461,42,463,465和466特别适用于此目的。 氨基酸在升高的发酵温度下的更大的溶解度允许简单地通过冷却从反应混合物中分离出氨基酸，然后将贫化的反应混合物泵送回发酵罐。 通过向发酵罐供应氧气至小于约20％的溶解氧的量来实现特别有利的产率。

    Process for the continuous enzymatic change of water soluble .alpha.-ketocarboxylic acids into the corresponding amino acids
    2.
    发明授权
    Process for the continuous enzymatic change of water soluble .alpha.-ketocarboxylic acids into the corresponding amino acids 失效
    将水溶性α-酮羧酸连续酶促转化为相应氨基酸的方法

    公开(公告)号：US4304858A

    公开(公告)日：1981-12-08

    申请号：US172446

    申请日：1980-07-25

    申请人： Christian Wandrey ,  Rolf Wichmann ,  Wolfgang Leuchtenberger ,  Maria-Regina Kula ,  Andreas Buckmann

    发明人： Christian Wandrey ,  Rolf Wichmann ,  Wolfgang Leuchtenberger ,  Maria-Regina Kula ,  Andreas Buckmann

    IPC分类号： C07C229/06 ,  C12M1/34 ,  C12P1/00 ,  C12P13/04 ,  C12P13/06 ,  C12P19/36 ,  C12P13/08

    CPC分类号： C12P13/06 ,  C12P1/00 ,  C12P13/04 ,  C12P19/36 ,  Y10S435/813

    摘要： Water soluble .alpha.-ketocarboxylic acids are continuously converted in a membrane reactor into the corresponding aminoacids. The conversion takes place in the presence of a substrate specific dehydrogenase, of ammonium ions and of a nicotinamide-adenine-dinucleotide (NAD.sup.+ /NADH) enlarged in molecular weight through linkage to a water soluble polymer as coenzyme. Simultaneously NADH is regenerated continuously from NAD.sup.+ in presence of a formate dehydrogenase and from formate ion. The membrane must have a mean pore diameter of 1 to 3 nm. As coenzyme there is employed 0.1 to 10 mmol/l of NAD.sup.+ /NADH present bound to a polyoxyethylene having an average molecular weight between 500 and 50,000. There is continuously supplied to the reactor a substrate stream which contains 50 to 100% of the maximum amount soluble, but not over 2,000 mmol/l, of the reacting .alpha.-ketocarboxylic acid in the form of a water soluble salt, an ammonium ion in an amount about equimolar to the amount of substrate and 100 to 6,000 mmol/l of a formate. There is maintained over the membrane a differential pressure of 0.1 to 15 bar. There is continuously drawn off behind the membrane a filtrate stream containing the aminoacid formed.

    摘要翻译： 水溶性α-酮羧酸在膜反应器中连续转化成相应的氨基酸。 通过与作为辅酶的水溶性聚合物连接，在底物特异性脱氢酶，铵离子和烟酰胺 - 腺嘌呤二核苷酸（NAD + / NADH）存在下进行转化，分子量增加。 同时NADH在甲酸脱氢酶和甲酸根离子存在下从NAD +连续再生。 膜的平均孔径必须为1〜3nm。 作为辅酶，使用0.1〜10mmol / l的NAD + / NADH，其与平均分子量在500〜50,000的聚氧乙烯结合。 向反应器中连续供应底物流，其含有50〜100％最大量可溶性但不超过2,000mmol / l的水溶性盐，铵离子形式的α-酮羧酸 相当于底物量的等摩尔量和100-6,000mmol / l甲酸盐的量。 在膜上保持0.1至15巴的压差。 在膜的后面连续抽出含有形成的氨基酸的滤液流。

    Process for the continuous enzymatic conversion of alpha-hydrocarboxylic acids into the corresponding optically active alpha-aminocarboxylic acids
    3.
    发明授权
    Process for the continuous enzymatic conversion of alpha-hydrocarboxylic acids into the corresponding optically active alpha-aminocarboxylic acids 失效
    将α-加氢羧酸连续酶促转化成相应的光学活性α-氨基羧酸的方法

    公开(公告)号：US4782020A

    公开(公告)日：1988-11-01

    申请号：US83882

    申请日：1987-08-10

    申请人： Wolfgang Leuchtenberger ,  Christian Wandrey ,  Maria-Regina Kula

    发明人： Wolfgang Leuchtenberger ,  Christian Wandrey ,  Maria-Regina Kula

    IPC分类号： C12P13/04 ,  C12P13/06 ,  C12P13/12 ,  C12P41/00 ,  C12Q1/32

    CPC分类号： C12P13/06 ,  C12P13/04 ,  C12P13/12 ,  Y10S435/813

    摘要： .alpha.-Hydroxycarboxylic acids are continuously converted into the corresponding optically active .alpha.- aminocarboxylic acids. The conversion is carried out in a membrane reactor in the presence of nicotinamide-adenine dinucleotide increased in molecular weight by bonding to a water soluble high molecular weight material, a dehydrogenase specific for the .alpha.-hydroxycarboxylic acid, a dehydrogenase specific for the corresponding .alpha.-amino-carboxylic acid and ammonium ions. There is continuously supplied to the membrane reactor an aqueous solution of the .alpha.-hydroxycarboxylic acid to be reacted, a substantially lesser amount of the corresponding .alpha.-ketocarboxy lic acid, and an amount of ammonium ion at least equivalent to the .alpha.-hydroxycarboxylic acid to be reacted. There is maintained over the membrane a difference in pressure 1 and 15 bar. Behind the membrane, there is continuously drawn off a filtrate stream containing the .alpha.-aminocarboxylic acid formed.

    摘要翻译： α-羟基羧酸连续转化为相应的光学活性α-氨基羧酸。 在通过结合到水溶性高分子量材料的烟酰胺 - 腺嘌呤二核苷酸增加分子量的存在下，在膜反应器中进行转化，对于α-羟基羧酸是特异性的脱氢酶，对于相应的α- 氨基羧酸和铵离子。 向膜反应器中连续供应待反应的α-羟基羧酸的水溶液，相当少量的相应的α-酮羧酸的丙酸，以及一定量的至少等同于α-羟基羧酸的铵离子至 被反应。 在膜上保持压力1和15巴的差异。 在膜的后面，连续地抽出含有形成的α-氨基羧酸的滤液流。

    Process for the continuous enzymatic change of water soluble .alpha.-ketocarboxylic acids into the corresponding .alpha.-hydroxycarboxylic acids
    5.
    发明授权
    Process for the continuous enzymatic change of water soluble .alpha.-ketocarboxylic acids into the corresponding .alpha.-hydroxycarboxylic acids 失效
    将水溶性α-酮羧酸连续酶促改变成相应的α-羟基羧酸的方法

    公开(公告)号：US4326031A

    公开(公告)日：1982-04-20

    申请号：US172444

    申请日：1980-07-25

    申请人： Christian Wandrey ,  Rolf Wichmann ,  Wolfgang Leuchtenberger ,  Maria-Regina Kula ,  Andreas Buckmann

    发明人： Christian Wandrey ,  Rolf Wichmann ,  Wolfgang Leuchtenberger ,  Maria-Regina Kula ,  Andreas Buckmann

    IPC分类号： C12N11/02 ,  C12P1/00 ,  C12P7/42 ,  C12P7/56

    CPC分类号： C12P1/00 ,  C12P7/42 ,  C12P7/56

    摘要： Water soluble .alpha.-ketocarboxylic acids are continuously converted in a membrane reactor into the corresponding .alpha.-hydrocarboxylic acids. The conversion takes place in the presence of a substrate specific dehydrogenase and of a nicotinamide-adenine-dinucleotide (NAD.sup.+ /NADH) enlarged in molecular weight through linkage to a water soluble polymer as coenzyme. Simultaneously NADH is regenerated continuously from NAD.sup.+ in presence of a formate dehydrogenase and from formate ion. The membrane must have a mean pore diameter of 1 to 3 nm. As coenzyme there is employed 0.1 to 10 mmol/l of NAD.sup.+ /NADH present bound to a water soluble polymer having an average molecular weight between 500 and 50,000. There is continuously supplied to the reactor a substrate stream which contains 50 to 100% of the maximum amount soluble, but not over 2,000 mmol/l, of the reacting .alpha.-ketocarboxylic acid in the form of a water soluble salt and 100 to 6,000 mmol/l of a formate. There is maintained over the membrane a differential pressure of 0.1 to 15 bar. There is continuously drawn off behind the membrane a filtrate stream containing the .alpha.-hydroxy acid formed.

    摘要翻译： 水溶性α-酮羧酸在膜反应器中连续转化成相应的α-羟基羧酸。 通过与作为辅酶的水溶性聚合物连接，在底物特异性脱氢酶和分子量增大的烟酰胺 - 腺嘌呤二核苷酸（NAD + / NADH）的存在下进行转化。 同时NADH在甲酸脱氢酶和甲酸根离子存在下从NAD +连续再生。 膜的平均孔径必须为1〜3nm。 作为辅酶，使用0.1〜10mmol / l的NAD + / NADH，其与平均分子量在500〜50,000的水溶性聚合物结合。 向反应器中连续供应底物物流，其含有50〜100％最大量可溶性但不超过2,000mmol / l的水溶性盐形式的α-酮羧酸反应物和100至6,000mmol / l的甲酸盐。 在膜上保持0.1至15巴的压差。 在膜的后面连续地抽出含有形成的α-羟基酸的滤液流。

    Process for the recovery of malic acid
    7.
    发明授权
    Process for the recovery of malic acid 失效
    回收苹果酸的方法

    公开(公告)号：US4772749A

    公开(公告)日：1988-09-20

    申请号：US563983

    申请日：1983-12-21

    申请人： Michael Karrenbauer ,  Axel Kleemann ,  Wolfgang Leuchtenberger ,  Rudi Moerck

    发明人： Michael Karrenbauer ,  Axel Kleemann ,  Wolfgang Leuchtenberger ,  Rudi Moerck

    IPC分类号： C07C59/245 ,  C07C51/00 ,  C07C51/42 ,  C07C67/00 ,  C12P7/46

    CPC分类号： C12P7/46

    摘要： The reaction mixture obtained in the enzymatic reaction of fumaric acid to form L-malic acid contains the L-malic acid and unreacted fumaric acid as their salts. To recover pure solutions of L-malic acid the reaction mixture is treated at 50.degree. to 150.degree. C. with cation exchangers. The eluate after concentration to 30 to 80 weight % content of L-malic acid is filtered. The pure L-malic acid is recovered by evaporating the solutions, in a given case after treatment with activated carbon.

    摘要翻译： 在富马酸的酶促反应中获得的形成L-苹果酸的反应混合物含有L-苹果酸和未反应的富马酸作为其盐。 为了回收L-苹果酸的纯溶液，将反应混合物用阳离子交换剂在50-150℃下处理。 过滤浓缩至30〜80重量％L-苹果酸含量的洗脱液。 通过蒸发溶液来回收纯L-苹果酸，在给定情况下用活性炭处理后。