CN100365115C - 产l-精氨酸的大肠杆菌及生产l-精氨酸的方法 - Google Patents
产l-精氨酸的大肠杆菌及生产l-精氨酸的方法 Download PDFInfo
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- CN100365115C CN100365115C CNB011218827A CN01121882A CN100365115C CN 100365115 C CN100365115 C CN 100365115C CN B011218827 A CNB011218827 A CN B011218827A CN 01121882 A CN01121882 A CN 01121882A CN 100365115 C CN100365115 C CN 100365115C
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- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
- C12P13/14—Glutamic acid; Glutamine
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Abstract
可以通过在培养基中培养大肠杆菌并从培养基中收集精氨酸而有效的生产精氨酸，其中该大肠杆菌能够产生精氨酸并能够利用乙酸从而可在培养基中产生和积聚精氨酸。
Description
技术领域
本发明涉及生产L-精氨酸的大肠杆菌和通过用大肠杆菌发酵生产L-精氨酸的方法。L-精氨酸是工业上有用的氨基酸，可以用作肝功能促进剂，氨基酸输注用品和各种氨基酸制品的成分。
背景技术
已知一些抗精氨酸的类似物和吡啶的大肠杆菌的突变体可以生产精氨酸(Pierard A.and Glansdorf N.，Mol.Gen.Genet.，118，235，1972.and Glansdorf N.，Biosynthesis of arginine andpolyamines. In″E. Coli and Salm.thyphimurium，1996)。另外，还有一些使用抗其它药物的大肠杆菌突变体或重组大肠杆菌的菌株的方法，其中在重组的大肠杆菌中导入了一种编码精氨酸生物合成途径酶的基因。
在大肠杆菌K12的精氨酸的生物合成途径中，每消耗1摩尔的乙酰辅酶A，将释放1摩尔的乙酸和产生1摩尔的精氨酸(图1)。由于有乙酸副产品产生，相当部分的碳源被消耗了；此外，乙酸的积聚还恶化了精氨酸生产株培养物的生长。
还已知大肠杆菌不能有效的利用乙酸作为碳源。
发明内容
根据以上的观点，本发明人设想如果生产精氨酸的菌株能够再利用乙酸的话，则精氨酸的产量可以会更高。因此，本发明的一个目的是提供能够利用乙酸的精氨酸生产菌株和利用该菌株生产精氨酸的方法。
于是本发明人就构建了能够利用乙酸并能够提高精氨酸的产率的大肠杆菌精氨酸生产者突变株。从而完成了本发明。
也就是说，本发明提供了能够生产精氨酸并能利用乙酸的大肠杆菌。
本发明还提供了生产精氨酸的方法，包括包括在培养基中培养能够利用乙酸和能够产生精氨酸的大肠杆菌以产生和积聚精氨酸的步骤，和从培养基中收集精氨酸的步骤。
在本发明中，氨基酸是L-构型的。
本发明将详述如下。
本发明的大肠杆菌能够利用乙酸并能够产生精氨酸。可以通过将利用乙酸的能力导入到能够产生精氨酸的大肠杆菌菌株或者通过将产生精氨酸的能力导入到具有利用乙酸能力的大肠杆菌菌株中从而得到同时能利用乙酸和产生精氨酸的菌株中。
对本发明来说，术语“能够产生精氨酸”指当本发明的大肠杆菌菌株培养在培养基中时能够在培养基中产生和积聚精氨酸。术语“能够利用乙酸”指相对于亲本菌株来说可以更有效的代谢乙酸或乙酸盐，例如，当该大肠杆菌菌株培养在含乙酸或乙酸盐作为唯一碳源的培养基中时，本发明所用的大肠杆菌菌株生长得比亲本菌株快。更具体的，可以这样说，如果该菌株在含乙酸或乙酸盐作为唯一碳源的培养基上培养时，其生长比亲本菌株快，就可以说该菌株可以利用乙酸；例如，在合适的条件下培养在含5g/l乙酸铵的液体基本培养基A中(如下文所述)。更具体的，当在合适的条件下，将该菌株培养在含乙酸或乙酸盐作为唯一碳源的培养基，例如，含有5g/l的乙酸铵的琼脂培养基上时，如果该菌株37℃，2天时形成了细菌菌落，就可以说该大肠杆菌菌株能够利用乙酸。术语“合适的条件”指温度，pH，空气供应或任选的对待培养的大肠杆菌菌株必需的营养。
作为获得本发明的大肠杆菌菌株的方法的一个例子，下面将介绍一个通过从一个能够产生精氨酸的大肠杆菌菌株诱导产生一个能够利用乙酸的突变体。
能够产生精氨酸的大肠杆菌的例子没用特别的限定，只要这样的大肠杆菌菌株能够被赋予利用乙酸的能力即可。这样的大肠杆菌的例子包括从大肠杆菌K-12，B，C或其衍生物培养得到精氨酸生产菌株。作为大肠杆菌精氨酸生产者的例子，可以列举如下：抗α-甲基甲硫氨酸，p-氟苯基丙氨酸，D-精氨酸，精氨酸氧肟酸盐，s-(2-氨乙基)-半胱氨酸，α-甲基丝氨酸，β-2-噻吩基丙氨酸或磺胺胍的突变体(日本专利申请公开56-106598)，导入了编码N-乙酰谷氨酸合成酶的argA基因的精氨酸生产株等(日本专利申请公开57-5693)。下文实施例中所描述的大肠杆菌菌株237也是一个优选的精氨酸生产菌株。菌株237已经被保藏在俄罗斯国立工业微生物保藏中心(VKPM)，保藏号VKPM B-7925，保藏日期2000年4月19日，并且在2001年5月18日根据布达佩斯条约转移到国际保藏。
如上所述，可以从精氨酸生产株获得能利用乙酸的突变株，例如，对精氨酸生产株进行突变处理并筛选能在含乙酸或乙酸盐作为唯一碳源的培养基上生长的菌株。可以通过例如，紫外照射或用人工致突变剂如1-甲基-3-硝基-1-亚硝基胍(NTG)和亚硝酸进行突变处理。对能够利用乙酸的突变株致突和筛选可以重复2次以上。
可以通过在培养基中培养上述的能利用乙酸和能产生精氨酸的大肠杆菌而在培养基中产生和积累精氨酸并从培养基中收集精氨酸。
在棒状杆菌中，由谷氨酸乙酰化为N-乙酰谷氨酸和N-乙酰谷氨酸脱乙酰化为鸟氨酸的反应是由同一个酶催化的，即鸟氨酸乙酰转移酶。另一方面，在大肠杆菌的生物合成途径中，乙酰化和脱乙酰化是不同的酶催化的，分别是N-乙酰谷氨酸合成酶和N-乙酰鸟氨酸酶。因此，如果可以利用副产品乙酸的话，其精氨酸的生产能力是未知的。
在本发明的生产精氨酸的方法中，可以使用与大肠杆菌发酵生产精氨酸类似的方式培养大肠杆菌，以及在液体培养基中收集和纯化精氨酸。
作为碳酸，可以使用糖类如葡萄糖，乳糖，半乳糖，果糖，或淀粉水解产物；醇类可以使用甘油或山梨糖醇；或有机酸如乙酸，富马酸，柠檬酸或琥珀酸。
作为氮源，可以使用无机铵盐，如硫酸铵，氯化铵，或磷酸铵；有机氮如大豆水解物；氨气或氨水。
还需要含有适量的物质如维生素B1和L-异亮氨酸或酵母提取物作为有机痕量营养物。除此之外，如果需要，还可以加入少量的磷酸钾，硫酸镁，铁离子，锰离子等。
培养优选在通气条件下进行16-72小时。培养温度控制在25-45℃，pH值控制在5-8。可以使用无机或有机酸，碱以及氨气等调节pH值。
可以结合离子交换树脂和其他已知的方法从发酵液中收集精氨酸。
具体实施方式
下面将参照实施利队本发明进行具体的描述。
实施例1：可以利用乙酸的突变体的诱导
从产精氨酸的突变体大肠杆菌菌株237，可以诱导出在含有乙酸铵(5g/l)作为唯一碳源和氮源的M9琼脂培养基上生长良好的突变株。菌株237是一个抗吡啶类似物6-氮尿吡啶的突变体，它是用1-甲基-3-硝基-亚硝基胍从大肠杆菌K12 ilvA：：Tn5诱导而来的。菌株237在含乙酸铵作为唯一碳源和氮源的M9琼脂培养基上生长很差。改菌株已经于2000年4月10日保藏在俄罗斯国立工业微生物保藏中心(VKPM)，保藏号是VKPM B-7925，并已经在2001年5月18日根据布达佩斯条约转移为国际保藏。
菌株237的细胞在L-肉汤中振荡(试管，37℃)培养过夜并离心收集之。然后将细胞重新悬浮于含有0.1mg/ml NTG的盐溶液中(0.8％)。在37℃与NTG接触30分钟后，离心得到细胞，用盐水洗涤2次并在基本培养基A上铺板，其中基本培养基A每1升水(pH 7.0)中含有5g乙酸铵，6g磷酸氢二钾，3g磷酸二氢钾，0.5g NaCl，0.1mg硫胺素，0.1g L-异亮氨酸，15g琼脂。
37℃，培养平板5天。收集2天内在平板上出现的菌落并用相同的琼脂平板划线纯化之。亲本菌株237只有在培养5天后才形成菌落。可利用乙酸的突变体的出现频率为6*10-5。测试了70个纯化菌株的精氨酸产力。约1/4的突变株比亲本菌株237产力高。其中，最好的产精氨酸的菌株是382。已经将菌株382于2000年4月10日保藏在俄罗斯国立工业微生物保藏中心，保藏号是VKPM B-7926，并于2001年5月18日根据布达佩斯条约转移为国际保藏。
实施例2：新突变体在乙酸盐上的生长
将2ml含乙酸铵(5g/l)或葡萄糖(5g/l)作为唯一碳源的液体基本培养基A(未加琼脂)放入试管中，接种一环新菌株382，另一个精氨酸生产菌株383和亲本菌株237，32℃振荡培养16小时。通过其在540nm的光密度确定培养物的生长。在培养开始时，培养基的光密度为大约0.05。结果如下表1。
表1
| 菌株 | 在液体培养基中生长16小时(OD540) | |
| 葡萄糖(0.5％) | 乙酸铵(0.5％) | |
| 237(亲本) | 1.8 | 0.4 |
| 382 | 1.5 | 1.0 |
| 383 | 1.6 | 0.7 |
实施例3：用新的L-精氨酸生产突变株通过试管发酵生产精氨酸
将新菌株382，383及其亲本菌株237培养在发酵培养基中。发酵培养基每1升自来水(pH7.2)含有60g葡萄糖，25g硫酸铵，2g KH2PO4，1g MgSO4.7H2O，0.1mg硫胺素，5g酵母提取物(Difco)，25g硫酸钙。将葡萄糖和白垩分别灭菌。将2ml培养基加入到试管中，接种一环待试微生物，32℃振荡培养3天。培养基中积累的精氨酸的量如下表2所示。
表2
| 菌株 | 精氨酸(g/l) |
| 237(亲本) | 5.1 |
| 382(可以利用乙酸的突变体) | 10.0 |
| 383(可以利用乙酸的突变体) | 7.7 |
实施例4：用新的产精氨酸的突变体通过发酵罐生产精氨酸
新的菌株382及其亲本菌株237在L-肉汤中32℃振荡培养8小时。然后，将得到的60ml种子培养物接种到1升的发酵罐中，其中发酵罐中含有0.5L发酵培养基，然后在32℃，700rpm搅拌培养，通气率为0.51/min。发酵培养基在1L自来水(pH 7.0)中含有100g葡萄糖，9g硫酸铵，1g KH2PO4，0.4g MgSO4.7H2O，0.02g FeSO4，0.02g MnSO4.7H2O，0.2g大豆水解产物总氮，0.3g L-异亮氨酸，0.4g硫胺素。在培养中，加入铵溶液(4.7M)以调节pH为7.0并提供氮源。培养42小时。培养基中积累的精氨酸的量和以葡萄糖为碳源的培养基中的精氨酸的产率如表3所示。
表3
| 菌株 | 精氨酸(g/l) | 葡萄糖培养基的产率(％) |
| 237(亲本) | 4.5 | 5.2 |
| 382(可以利用乙酸的突变体) | 19.3 | 23.9 |
与亲本菌株相比，可以利用乙酸的突变株的精氨酸的产率更高。
Claims (6)
1.能够产生L-精氨酸并能够利用乙酸盐的大肠杆菌，其中该大肠杆菌是保藏号为VKPM B-7925的大肠杆菌菌株237的衍生物。
2.权利要求1的大肠杆菌，其中当该大肠杆菌培养在含有乙酸或乙酸盐作为唯一的碳源的琼脂培养基上时，在37℃，2天内形成菌落。
3.权利要求1或2的大肠杆菌，其中该细菌是保藏号为VKPM B-7926的大肠杆菌菌株382。
4.一种生产L-精氨酸的方法，包括在培养基中培养权利要求1的大肠杆菌以产生和积聚L-精氨酸的步骤，和从培养基中收集L-精氨酸的步骤。
5.一种生产L-精氨酸的方法，包括在培养基中培养权利要求2的大肠杆菌以产生和积聚L-精氨酸的步骤，和从培养基中收集L-精氨酸的步骤。
6.一种生产L-精氨酸的方法，包括在培养基中培养权利要求3的大肠杆菌以产生和积聚L-精氨酸的步骤，和从培养基中收集L-精氨酸的步骤。
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Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2208640C2 (ru) * | 2000-07-06 | 2003-07-20 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | СПОСОБ ПОЛУЧЕНИЯ L-АРГИНИНА, ШТАММ Escherichia coli - ПРОДУЦЕНТ L-АРГИНИНА |
| US7606210B2 (en) * | 2004-09-10 | 2009-10-20 | Nivis, Llc | System and method for message consolidation in a mesh network |
| MX2007004166A (es) | 2004-10-07 | 2007-10-23 | Ajinomoto Kk | Proceso para producir una sustancia basica. |
| RU2004137719A (ru) | 2004-12-23 | 2006-06-10 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) (RU) | Способ получения l-аминокислот с использованием бактерий семейства enterobacteriaceae |
| JP2009118740A (ja) | 2006-03-03 | 2009-06-04 | Ajinomoto Co Inc | Ｌ−アミノ酸の製造法 |
| EP2351830B1 (en) | 2006-03-23 | 2014-04-23 | Ajinomoto Co., Inc. | A method for producing an L-amino acid using bacterium of the Enterobacteriaceae family with attenuated expression of a gene coding for small RNA |
| JP2009165355A (ja) | 2006-04-28 | 2009-07-30 | Ajinomoto Co Inc | Ｌ−アミノ酸を生産する微生物及びｌ−アミノ酸の製造法 |
| RU2006143864A (ru) | 2006-12-12 | 2008-06-20 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) (RU) | СПОСОБ ПОЛУЧЕНИЯ L-АМИНОКИСЛОТ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ СЕМЕЙСТВА ENTEROBACTERIACEAE, В КОТОРОЙ ОСЛАБЛЕНА ЭКСПРЕССИЯ ГЕНОВ cynT, cynS, cynX, ИЛИ cynR, ИЛИ ИХ КОМБИНАЦИИ |
| JP2010041920A (ja) | 2006-12-19 | 2010-02-25 | Ajinomoto Co Inc | Ｌ−アミノ酸の製造法 |
| BRPI0703692B1 (pt) | 2006-12-25 | 2016-12-27 | Ajinomoto Kk | método para se obter os cristais de um hidrocloreto de aminoácido básico compreendendo gerar um aminoácido básico usando células microbianas por fermentação em um caldo de fermentação ou por um método enzimático em uma solução de reação de enzima usando as células como catalisadores |
| CN101627110B (zh) | 2007-01-22 | 2014-08-13 | 味之素株式会社 | 生产l-氨基酸的微生物和l-氨基酸的生产方法 |
| JP2010110217A (ja) | 2007-02-22 | 2010-05-20 | Ajinomoto Co Inc | Ｌ−アミノ酸生産菌及びｌ−アミノ酸の製造法 |
| JP2010130899A (ja) | 2007-03-14 | 2010-06-17 | Ajinomoto Co Inc | Ｌ−グルタミン酸系アミノ酸生産微生物及びアミノ酸の製造法 |
| RU2396336C2 (ru) | 2007-09-27 | 2010-08-10 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) | СПОСОБ ПОЛУЧЕНИЯ АМИНОКИСЛОТ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ, ПРИНАДЛЕЖАЩЕЙ К РОДУ Escherichia |
| JP2011067095A (ja) | 2008-01-10 | 2011-04-07 | Ajinomoto Co Inc | 発酵法による目的物質の製造法 |
| KR20100120663A (ko) | 2008-01-23 | 2010-11-16 | 아지노모토 가부시키가이샤 | Ｌ-아미노산의 제조법 |
| RU2008105793A (ru) | 2008-02-19 | 2009-08-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) (RU) | Способ конструирования оперонов, содержащих трансляционно сопряженные гены, бактерия, содержащая такой оперон, способ продукции полезного метаболита и способ мониторинга экспрессии гена |
| WO2010027022A1 (ja) | 2008-09-05 | 2010-03-11 | 味の素株式会社 | Ｌ－アミノ酸生産菌及びｌ－アミノ酸の製造法 |
| EP2336347B1 (en) | 2008-09-08 | 2017-03-15 | Ajinomoto Co., Inc. | An l-amino acid-producing microorganism and a method for producing an l-amino acid |
| WO2010084995A2 (en) | 2009-01-23 | 2010-07-29 | Ajinomoto Co.,Inc. | A method for producing an l-amino acid |
| CN102471790B (zh) | 2009-07-29 | 2014-10-29 | 味之素株式会社 | 产生l-氨基酸的方法 |
| RU2010101135A (ru) | 2010-01-15 | 2011-07-20 | Закрытое акционерное общество "Научно-исследовательский институт "Аджиномото-Генетика" (ЗАО АГРИ) (RU) | Бактерия семейства enterobacteriaceae - продуцент l-аспартата или метаболитов, производных l-аспартата, и способ получения l-аспартата или метаболитов, производных l-аспартата |
| RU2460793C2 (ru) | 2010-01-15 | 2012-09-10 | Закрытое акционерное общество "Научно-исследовательский институт "Аджиномото-Генетика" (ЗАО АГРИ) | Способ получения l-аминокислот с использованием бактерий семейства enterobacteriaceae |
| JP2013074795A (ja) | 2010-02-08 | 2013-04-25 | Ajinomoto Co Inc | 変異型ｒｐｓＡ遺伝子及びＬ−アミノ酸の製造法 |
| RU2471868C2 (ru) | 2010-02-18 | 2013-01-10 | Закрытое акционерное общество "Научно-исследовательский институт "Аджиномото-Генетика" (ЗАО АГРИ) | Мутантная аденилатциклаза, днк, кодирующая ее, бактерия семейства enterobacteriaceae, содержащая указанную днк, и способ получения l-аминокислот |
| RU2010122646A (ru) | 2010-06-03 | 2011-12-10 | Закрытое акционерное общество "Научно-исследовательский институт "Аджиномото-Генетика" (ЗАО АГРИ) (RU) | Способ получения l-аминокислоты с использованием бактерии семейства enterobacteriaceae, в которой ослаблена экспрессия генов, кодирующих транспортер лизина/аргинина/орнитина |
| RU2471870C2 (ru) | 2010-06-03 | 2013-01-10 | Закрытое акционерное общество "Научно-исследовательский институт "Аджиномото-Генетика" (ЗАО АГРИ) | СПОСОБ ПОЛУЧЕНИЯ L-АРГИНИНА И L-ЦИТРУЛЛИНА С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ СЕМЕЙСТВА ENTEROBACTERIACEAE, В КОТОРОЙ ОСЛАБЛЕНА ЭКСПРЕССИЯ ГЕНА pepA |
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| RU2501858C2 (ru) * | 2010-07-21 | 2013-12-20 | Закрытое акционерное общество "Научно-исследовательский институт "Аджиномото-Генетика" (ЗАО АГРИ) | СПОСОБ ПОЛУЧЕНИЯ L-АМИНОКИСЛОТЫ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ СЕМЕЙСТВА Enterobacteriaceae |
| JP2014036576A (ja) | 2010-12-10 | 2014-02-27 | Ajinomoto Co Inc | Ｌ−アミノ酸の製造法 |
| RU2011134436A (ru) | 2011-08-18 | 2013-10-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО "АГРИ") | Способ получения l-аминокислоты с использованием бактерии семейства enterobacteriaceae, обладающей повышенной экспрессией генов каскада образования флагелл и клеточной подвижности |
| KR20140091742A (ko) | 2011-11-11 | 2014-07-22 | 아지노모토 가부시키가이샤 | 발효법에 의한 목적 물질의 제조법 |
| RU2550269C2 (ru) | 2012-08-17 | 2015-05-10 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО "АГРИ") | СПОСОБ ПОЛУЧЕНИЯ L-АРГИНИНА С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ СЕМЕЙСТВА Enterobacteriaceae, СОДЕРЖАЩЕЙ N-АЦЕТИЛОРНИТИНДЕАЦЕТИЛАЗУ С НАРУШЕННОЙ АКТИВНОСТЬЮ |
| RU2013118637A (ru) | 2013-04-23 | 2014-10-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО "АГРИ") | СПОСОБ ПОЛУЧЕНИЯ L-АМИНОКИСЛОТ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ СЕМЕЙСТВА ENTEROBACTERIACEAE, В КОТОРОЙ РАЗРЕГУЛИРОВАН ГЕН yjjK |
| JP2016165225A (ja) | 2013-07-09 | 2016-09-15 | 味の素株式会社 | 有用物質の製造方法 |
| RU2013140115A (ru) | 2013-08-30 | 2015-03-10 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО "АГРИ") | СПОСОБ ПОЛУЧЕНИЯ L-АМИНОКИСЛОТ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ СЕМЕЙСТВА Enterobacteriaceae, В КОТОРОЙ НАРУШЕНА ЭКСПРЕССИЯ КЛАСТЕРА ГЕНОВ znuACB |
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| RU2014105547A (ru) | 2014-02-14 | 2015-08-20 | Адзиномото Ко., Инк. | СПОСОБ ПОЛУЧЕНИЯ L-АМИНОКИСЛОТ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ СЕМЕЙСТВА ENTEROBACTERIACEAE, ИМЕЮЩЕЙ СВЕРХЭКСПРЕССИРУЕМЫЙ ГЕН yajL |
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| JP7066977B2 (ja) | 2017-04-03 | 2022-05-16 | 味の素株式会社 | Ｌ－アミノ酸の製造法 |
| WO2020071538A1 (en) | 2018-10-05 | 2020-04-09 | Ajinomoto Co., Inc. | Method for producing target substance by bacterial fermentation |
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| JP2020162549A (ja) | 2019-03-29 | 2020-10-08 | 味の素株式会社 | 制御装置、制御方法およびプログラムならびに有機化合物の製造方法 |
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| CN110484483A (zh) * | 2019-08-09 | 2019-11-22 | 山东汇冠康博生物科技有限公司 | 一种大肠杆菌菌株的制备方法 |
| JP7655312B2 (ja) | 2019-09-25 | 2025-04-02 | 味の素株式会社 | 細菌の発酵によるｌ－アミノ酸の製造方法 |
| JP7588014B2 (ja) | 2021-03-22 | 2024-11-21 | 株式会社日立製作所 | Ｃｏ２資化微生物のスクリーニング法 |
| US20240117393A1 (en) | 2022-09-30 | 2024-04-11 | Ajinomoto Co., Inc. | Method for producing l-amino acid |
| CN116355814B (zh) * | 2023-05-18 | 2023-07-25 | 欧铭庄生物科技(天津)有限公司滨海新区分公司 | 一株大肠埃希氏菌及其在发酵生产l-精氨酸中的应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4430430A (en) * | 1980-06-13 | 1984-02-07 | Ajinomoto Co., Inc. | Method for producing L-arginine by fermentation |
| US5017482A (en) * | 1986-09-22 | 1991-05-21 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing L-arginine |
| CN1258736A (zh) * | 1998-11-02 | 2000-07-05 | 味之素株式会社 | 制备l－精氨酸的方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56106598A (en) * | 1980-01-30 | 1981-08-24 | Ajinomoto Co Inc | Preparation of l-arginine by fermentation method |
| JPS6066989A (ja) * | 1983-09-24 | 1985-04-17 | Kyowa Hakko Kogyo Co Ltd | Ｌ−アルギニンの製造法 |
| US5976843A (en) | 1992-04-22 | 1999-11-02 | Ajinomoto Co., Inc. | Bacterial strain of Escherichia coli BKIIM B-3996 as the producer of L-threonine |
| US5175107A (en) | 1988-10-25 | 1992-12-29 | Ajinomoto Co., Inc. | Bacterial strain of escherichia coli bkiim b-3996 as the producer of l-threonine |
| RU2209246C2 (ru) | 2000-01-26 | 2003-07-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | Малая субъединица изозима iii и изозим iii синтетазы ацетогидроксикислот из escherichia coli, фрагмент днк (варианты), штамм бактерии escherichia coli - продуцент l-валина (варианты) и способ получения l-валина |
| JP4682454B2 (ja) | 2000-06-28 | 2011-05-11 | 味の素株式会社 | 新規変異型ｎ−アセチルグルタミン酸合成酵素及びｌ−アルギニンの製造法 |
| RU2207371C2 (ru) | 2000-09-26 | 2003-06-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | Способ получения l-аминокислот семейства l-глутаминовой кислоты, штамм бактерии escherichia coli - продуцент l-аминокислоты (варианты) |
| RU2208640C2 (ru) | 2000-07-06 | 2003-07-20 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | СПОСОБ ПОЛУЧЕНИЯ L-АРГИНИНА, ШТАММ Escherichia coli - ПРОДУЦЕНТ L-АРГИНИНА |
| RU2264459C2 (ru) | 2001-08-03 | 2005-11-20 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | Новая мутантная карбамоилфосфатсинтетаза и способ продукции соединений - производных карбамоилфосфата |
| RU2230114C2 (ru) | 2001-11-30 | 2004-06-10 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | Мутантная глутаминсинтетаза, фрагмент днк, штамм escherichia coli - продуцент l-глутамина и способ получения l-аминокислот |
-
2000
- 2000-07-06 RU RU2000117677/13A patent/RU2208640C2/ru active
-
2001
- 2001-06-14 JP JP2001180211A patent/JP4734775B2/ja not_active Expired - Lifetime
- 2001-06-18 EP EP01114588A patent/EP1170358B1/en not_active Expired - Lifetime
- 2001-06-18 DE DE60133973T patent/DE60133973D1/de not_active Expired - Lifetime
- 2001-06-18 ES ES01114588T patent/ES2305015T3/es not_active Expired - Lifetime
- 2001-06-22 US US09/886,254 patent/US6841365B2/en not_active Expired - Lifetime
- 2001-06-28 CN CNB011218827A patent/CN100365115C/zh not_active Expired - Lifetime
-
2004
- 2004-08-25 US US10/924,798 patent/US7052884B2/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4430430A (en) * | 1980-06-13 | 1984-02-07 | Ajinomoto Co., Inc. | Method for producing L-arginine by fermentation |
| US5017482A (en) * | 1986-09-22 | 1991-05-21 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing L-arginine |
| CN1258736A (zh) * | 1998-11-02 | 2000-07-05 | 味之素株式会社 | 制备l－精氨酸的方法 |
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| CN1332250A (zh) | 2002-01-23 |
| US20050026259A1 (en) | 2005-02-03 |
| JP4734775B2 (ja) | 2011-07-27 |
| JP2002017342A (ja) | 2002-01-22 |
| RU2208640C2 (ru) | 2003-07-20 |
| ES2305015T3 (es) | 2008-11-01 |
| US6841365B2 (en) | 2005-01-11 |
| EP1170358A1 (en) | 2002-01-09 |
| US20020034793A1 (en) | 2002-03-21 |
| DE60133973D1 (de) | 2008-06-26 |
| EP1170358B1 (en) | 2008-05-14 |
| US7052884B2 (en) | 2006-05-30 |
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