CN107287196B - ilv衰减子的突变体、相关工程菌及其在生产缬氨酸中的应用 - Google Patents
ilv衰减子的突变体、相关工程菌及其在生产缬氨酸中的应用 Download PDFInfo
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- CN107287196B CN107287196B CN201710388774.XA CN201710388774A CN107287196B CN 107287196 B CN107287196 B CN 107287196B CN 201710388774 A CN201710388774 A CN 201710388774A CN 107287196 B CN107287196 B CN 107287196B
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Abstract
本发明公开了一种ilv衰减子的突变体、相关工程菌及其在生产缬氨酸中的应用。本发明首先保护ilv衰减子突变体,为序列表的序列2第n1至n2位核苷酸所示的DNA分子;129≤n1≤148,155≤n2≤215。本发明还保护将ilvLXGMED操纵子基因中从ilv衰减子的第1至n4位去除得到的解除反馈阻遏的ilvLXGMED操纵子基因;128≤n4≤147。本发明还保护解除微生物中ilvLXGMED操纵子反馈阻遏的方法:删除ilvLXGMED操纵子基因中从ilv衰减子的第1至n4位。采用本发明提供的方案,可以显著提高缬氨酸及其衍生物产量,对于缬氨酸及其衍生物的生产领域具有重大的应用推广价值。
Description
技术领域
本发明属于生物技术领域,具体涉及一种ilv衰减子的突变体,以及含有该突变体的工程菌,以及该工程菌在发酵生产缬氨酸中的应用。
背景技术
L-缬氨酸是人体必需的8种氨基酸之一,与亮氨酸、异亮氨酸统称为分支链氨基酸。由于它特殊的结构和功能,L-缬氨酸在人和动物生命代谢中具有重要作用。L-缬氨酸是食品行业中常用的风味剂、营养增强剂。L-缬氨酸可作为动物的营养补充产品,用于饲料添加剂,能改善禽畜的免疫机能。医药上,高纯度的L-缬氨酸常被用于制造复合氨基酸输液或氨基酸注射液,还可用于合成抗高血压药和抗肿瘤药物等。此外,L-缬氨酸也可用于抗生素、除草剂以及化妆品等领域。目前国内外工业化生产L-缬氨酸的主要方法是微生物发酵法。然而,微生物中L-缬氨酸的合成途径及调控方式较复杂,是高效发酵生产L-缬氨酸及其衍生物的关键限制因素。
微生物合成氨基酸(如L-组氨酸、L-苏氨酸、L-苯丙氨酸、L-亮氨酸、L-缬氨酸和L-色氨酸等)的操纵子基因的转录表达存在衰减调节机制。当胞内特定氨基酸浓度较高时,氨基酸操纵子的转录提前终止。相反地,当胞内特定氨基酸缺乏时,RNA聚合酶转录氨基酸操纵子。
生物法生产L-缬氨酸或其衍生物的过程中,胞内L-缬氨酸逐步积累,通过上述衰减调控机制反馈阻遏ilvLXGMED操纵子的表达,不利于L-缬氨酸或其衍生物的生物合成。因此,高效解除缬氨酸对ilvLXGMED操纵子的衰减调控,是生物合成L-缬氨酸及其衍生物的关键。
发明内容
本发明的目的是提供一种ilv衰减子的突变体、相关工程菌及其在生产缬氨酸中的应用。
本发明首先保护一种DNA分子甲(ilv衰减子突变体),为如下(a1)、(a2)或(a3):
(a1)序列表的序列2第n1至n2位核苷酸所示的DNA分子;n1为129以上148以下的自然数(n1优选为137),n2为155以上215以下的自然数(n2具体可为155以上185以下的自然数或186以上215以下的自然数,更具体可为155、185或215);
(a2)在(a1)的末端连接标签序列得到的DNA分子;
(a3)在(a1)的末端连接连接序列得到的DNA分子。
ilv衰减子突变体为ilv衰减子截短体或ilv衰减子变体。ilv衰减子截短体如序列表的序列2第n1至155位核苷酸所示。ilv衰减子变体如序列表的序列2第n1至n3位核苷酸所示,n3为156以上215以下的自然数(n3具体可为156以上185以下的自然数或186以上215以下的自然数,更具体可为185或215)。
本发明还保护所述DNA分子甲在促进下游目的基因表达中的应用。所述应用中,所述DNA分子甲作为调控元件。所述应用中,所述DNA分子甲位于所述目的基因的启动子和所述目的基因的起始密码子之间。所述应用中,所述启动子具体可为序列表的序列1所示的启动子Pthr-trc。所述应用中,所述目的基因具体可为序列表的序列3所示的gfp基因。
本发明还保护DNA分子乙,自上游至下游依次包括:所述DNA分子甲和目的基因。所述目的基因具体可为序列表的序列3所示的gfp基因。
本发明还保护DNA分子丙,自上游至下游依次包括:启动子、所述DNA分子甲、目的基因和终止子。所述启动子具体可为序列表的序列1所示的启动子Pthr-trc。所述目的基因具体可为序列表的序列3所示的gfp基因。所述终止子具体可为CTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTG。
所述DNA分子甲或所述DNA分子乙或所述DNA分子丙中,不具有ilv衰减子的第1至n4位核苷酸,n4为128以上147以下的自然数(n4优选为136)。
所述DNA分子乙自上游至下游依次由如下元件组成:序列表的序列2第137至215位核苷酸,连接序列“GGTTCTGGTTCTGGTTCT”,序列表的序列3所示的gfp基因。
所述DNA片段丙自上游至下游依次由如下元件组成:序列表的序列1所示的启动子Pthr-trc,限制性内切酶HindIII的酶切识别序列,序列表的序列2第137至215位核苷酸,连接序列“GGTTCTGGTTCTGGTTCT”,序列表的序列3所示的gfp基因,终止子序列CTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTG。
本发明还保护DNA分子丁(解除反馈阻遏的ilvLXGMED操纵子基因,又称ilvLXGMED操纵子基因突变体),是将ilvLXGMED操纵子基因中从ilv衰减子第1位开始计数的第1至n4位核苷酸去除得到的DNA分子;n4为128以上147以下的自然数(n4优选为136)。
所述DNA分子丁具体可为序列表的序列2第137至5009位核苷酸所示的双链DNA分子。
本发明还保护DNA分子戊,自上游至下游依次包括如下元件:启动子、所述DNA分子丁和终止子。所述启动子具体可为序列表的序列6所示的启动子PJJ。所述终止子具体可为CTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTG。
所述DNA分子戊自上游至下游依次由如下元件组成:序列表的序列6所示的启动子PJJ,限制性内切酶BamH I的酶切识别序列,序列表的序列2第137至5057位核苷酸所示的双链DNA分子。
含有所述DNA分子丁或所述DNA分子戊的重组载体也属于本发明的保护范围。
含有所述DNA分子丁或所述DNA分子戊的重组菌也属于本发明的保护范围。
所述重组菌是将所述DNA分子丁或所述DNA分子戊导入出发菌得到的。所述出发菌可为埃希氏菌属细菌或棒杆菌属细菌。所述埃希氏菌属细菌具体可为大肠杆菌,更具体可为大肠杆菌K-12或其衍生菌株,更具体可为大肠杆菌K12MG1655或E.coli K-12MG1655△ilvA。所述棒杆菌属细菌具体可为谷氨酸棒杆菌,例如谷氨酸棒杆菌13032等。
E.coli K-12MG1655△ilvA是将大肠杆菌K12MG1655基因组中编码IlvA蛋白的基因敲除得到的菌株。E.coli K-12MG1655△ilvA是将大肠杆菌K12MG1655基因组中编码IlvA蛋白的基因的开放阅读框敲除得到的菌株。所述敲除的实现方法具体可为向大肠杆菌K12MG1655中导入干扰片段或干扰质粒。所述干扰片段具体可为如下DNA分子:自上游至下游依次由序列表的序列4第140-637位核苷酸所示的上游区段和序列表的序列4第2183-2712位核苷酸所示的下游区段组成。所述干扰质粒具体可为将所述干扰片段插入pKOV质粒得到的重组质粒。
IlvA蛋白为如下(b1)或(b2):
(b1)由序列表中序列5所示的氨基酸序列组成的蛋白质;
(b2)将序列的氨基酸序列5经过一个或几个氨基酸残基的取代和/或缺失和/或添加且具有相同功能的由序列5衍生的蛋白质。
编码IlvA蛋白的基因具体可如序列表的序列4所示。
编码IlvA蛋白的基因的开放阅读框具体可为序列表的序列4第638-2182位核苷酸。
本发明还保护所述重组菌在制备缬氨酸中的应用。
应用所述重组菌生产缬氨酸时,采用葡萄糖作为碳源。
应用所述重组菌生产缬氨酸时,采用发酵培养基培养所述重组菌。
所述发酵培养基可以是丰富培养基,也可以是无机盐培养基。培养基包含碳源、氮源、无机离子、抗生素和其它的营养因子。作为碳源,可以使用葡萄糖、乳糖、半乳糖等糖类;也可以是甘油、甘露醇等醇类;也可以使用葡萄糖酸、柠檬酸、丁二酸等有机酸类。作为氮源,可以使用氨水、硫酸铵、磷酸铵、氯化铵等无机氮源;也可以使用玉米浆、豆粕水解液、毛发粉、酵母提取物、蛋白胨等有机氮源。无机离子包含铁、钙、镁、锰、钼、钴、铜、钾等离子中的一种或多种。其它营养因子还包括生物素、维生素B1、吡哆醛等维生素。
所述发酵培养基中的碳源为葡萄糖。
所述发酵培养基具体可为:发酵培养基:葡萄糖20.0g/L、硫酸铵15.0g/L、磷酸二氢钾2.0g/L、七水硫酸镁2.0g/L、酵母粉2.0g/L、异亮氨酸0.6g/L、碳酸钙15.0g/L、微量元素混合液5mL/L,余量为水。
微量元素混合液:FeSO4·7H2O 10g/L、CaCl2 1.35g/L、ZnSO4·7H2O 2.25g/L、MnSO4·4H2O 0.5g/L、CuSO4·5H2O 1g/L、(NH4)6Mo7O24·4H2O 0.106g/L、Na2B4O7·10H2O0.23g/L、CoCl2·6H2O 0.48g/L、35%HCl 10mL/L,余量为水。
所述培养的条件具体可为:37℃、220rpm震荡培养36h。
所述培养的条件具体可为:将种子液以3%的接种量接种至发酵培养基中,37℃、220rpm震荡培养36h。种子液的制备方法如下:将重组菌接种至液体LB培养基中,37℃、220rpm振荡培养12h,得到种子液。所述种子液的OD600nm值具体可为5.0。
所述培养的过程中进行如下过程控制:培养过程中,用氨水调节反应体系的pH值使其维持在6.8-7.0;培养过程中,每隔3-4h取样一次,检测葡萄糖含量,当体系中的葡萄糖含量低于5g/L时,补加葡萄糖并使体系中的葡萄糖浓度达到10g/L。
本发明还保护一种提高微生物生产缬氨酸的能力的方法,包括如下步骤:删除微生物的ilvLXGMED操纵子基因中从ilv衰减子第1位开始计数的第1至n4位核苷酸;n4为128以上147以下的自然数(n4优选为136)。所述微生物为具有ilvLXGMED操纵子的微生物。所述微生物具体可为埃希氏菌属微生物。所述埃希氏菌属微生物具体可为大肠杆菌,更具体可为大肠杆菌K-12或其衍生菌株,更具体可为大肠杆菌K12MG1655或E.coli K-12MG1655△ilvA。
本发明还保护一种解除微生物中ilvLXGMED操纵子反馈阻遏的方法,包括如下步骤:删除微生物的ilvLXGMED操纵子基因中从ilv衰减子第1位开始计数的第1至n4位核苷酸;n4为128以上147以下的自然数(n4优选为136)。所述微生物为具有ilvLXGMED操纵子的微生物。所述微生物具体可为埃希氏菌属微生物。所述埃希氏菌属微生物具体可为大肠杆菌,更具体可为大肠杆菌K-12或其衍生菌株,更具体可为大肠杆菌K12MG1655或E.coli K-12MG1655△ilvA。
以上任一所述ilvLXGMED操纵子可为来源于埃希氏菌属微生物的ilvLXGMED操纵子,具体可为来源于大肠杆菌的ilvLXGMED操纵子。埃希氏菌属微生物并不特别限定用哪一种微生物,若野生型株用作含有ilvLXGMED操纵子的DNA供体株,可以得到含有野生型ilvLXGMED操纵子的DNA。然而,大肠杆菌K-12株不表达活性的ilvG基因,因此本发明的ilvG基因来源于大肠杆菌BL21株的染色体。
以上任一所述ilvLXGMED操纵子基因包括ilv衰减子、编码IlvX蛋白的基因,编码IlvG蛋白(乙酰乳酸合酶)的基因、编码IlvM蛋白(乙酰乳酸合酶)的基因、编码IlvE蛋白(支链氨基酸转氨酶)的基因和编码IlvD蛋白(二羟酸脱水酶)的基因。
所述IlvX蛋白可为如下(c1)或(c2):
(c1)由序列表中序列7所示的氨基酸序列组成的蛋白质;
(c2)将序列的氨基酸序列7经过一个或几个氨基酸残基的取代和/或缺失和/或添加且具有相同功能的由序列7衍生的蛋白质。
IlvG蛋白可为如下(d1)或(d2):
(d1)由序列表中序列8所示的氨基酸序列组成的蛋白质;
(d2)将序列的氨基酸序列8经过一个或几个氨基酸残基的取代和/或缺失和/或添加且具有乙酰乳酸合酶功能的由序列8衍生的蛋白质。
IlvM蛋白可为如下(e1)或(e2):
(e1)由序列表中序列9所示的氨基酸序列组成的蛋白质;
(e2)将序列的氨基酸序列9经过一个或几个氨基酸残基的取代和/或缺失和/或添加且具有乙酰乳酸合酶功能的由序列9衍生的蛋白质。
IlvE蛋白可为如下(f1)或(f2):
(f1)由序列表中序列10所示的氨基酸序列组成的蛋白质;
(f2)将序列的氨基酸序列10经过一个或几个氨基酸残基的取代和/或缺失和/或添加且具有支链氨基酸转氨酶功能的由序列10衍生的蛋白质。
IlvD蛋白可为如下(g1)或(g2):
(g1)由序列表中序列11所示的氨基酸序列组成的蛋白质;
(g2)将序列的氨基酸序列11经过一个或几个氨基酸残基的取代和/或缺失和/或添加且具有二羟酸脱水酶功能的由序列11衍生的蛋白质。
编码IlvX蛋白的基因具体可如序列表的序列2第186-236位核苷酸所示。
编码IlvG蛋白的基因具体可如序列表的序列2第239-1885位核苷酸所示。
编码IlvM蛋白的基因具体可如序列表的序列2第1882-2145位核苷酸所示。
编码IlvE蛋白的基因具体可如序列表的序列2第2165-3094位核苷酸所示。
编码IlvD蛋白的基因具体可如序列表的序列2第3159-5009位核苷酸所示。
ilv衰减子如序列表的序列2第1至155位核苷酸所示。
ilvLXGMED操纵子基因具体可如序列表的序列2所示。
ilvLXGMED操纵子基因具体可如序列表的序列2第1-5009位核苷酸所示。
以上任一所述缬氨酸具体可为L-缬氨酸。
本发明通过去除ilv衰减子的特定序列,意外的获得了可以显著提高基因表达水平的ilv衰减子突变体。本发明通过删除衰减子中编码前导肽的基因ilvL和终止子茎环结构中前段反向互补回文序列,可以显著提高后续基因的表达水平。显而易见,根据本专利的试验结果,本领域技术人员可轻易推论得到,在本发明保护的ilv衰减子突变体上同时保留上述衰减子终止子茎环结构中前段反向互补回文序列的部分序列,但尚未形成稳定的茎环结构,同样可能得到相似性能的ilv衰减子突变体和ilvLXGMED操纵子基因突变体。因此,这种类似的改造ilv衰减子的方法也在本专利的保护范围之中。显而易见,在改造菌株染色体上的ilv衰减子同时删除ilvL开放阅读框上游若干碱基对,也在本发明的保护范围内。显而易见,本发明解除大肠杆菌的ilv衰减子的方法,同样可应用于其它菌属的ilv衰减子。本发明可以用于生产缬氨酸,因此,显而易见,本发明还可用于缬氨酸代谢途径下游化合物的生物合成。
采用本发明提供的方案,可以显著提高缬氨酸及其衍生物产量,对于缬氨酸及其衍生物的生产领域具有极其重大的应用推广价值。
具体实施方式
以下的实施例便于更好地理解本发明,但并不限定本发明。下述实施例中的实验方法,如无特殊说明,均为常规方法。下述实施例中所用的试验材料,如无特殊说明,均为自常规生化试剂商店购买得到的。以下实施例中的定量试验,均设置三次重复实验,结果取平均值。下述实施例中如未特别指明,实施例中所用的技术手段为本领域技术人员所熟知的常规手段和市售的常用仪器、试剂,可参见《分子克隆实验指南(第3版)》(科学出版社)、《微生物学实验(第4版)》(高等教育出版社)以及相应仪器和试剂的厂商说明书等参考。ATCC:https://www.atcc.org/。
大肠杆菌K12MG1655:ATCC编号为700926。pACYC184质粒:NEB公司,产品目录号E4152S。pGFPuv载体:Clontech Laboratories,Inc.,Catalog No.632312。pKOV质粒:Addgene公司,产品目录号为25769。大肠杆菌EC135:记载于如下文献:Zhang et al,PlosGenetics,2012,8(9):e1002987。
实施例1、衰减子突变体调控gfp基因的表达
一、构建重组质粒pACYC184-Pthr-trc
1、合成序列表的序列1所示的双链DNA分子(启动子Pthr-trc)。
2、以大肠杆菌K12MG1655的基因组DNA为模板,采用WY1947和WY1948组成的引物对进行PCR扩增,得到PCR扩增产物。
WY1947:CTAGTCTAGAGCTTTTCATTCTGACTGCAAC;
WY1948:CCCAAGCTT ACATTATACGAGCCGGATGATTAATTGTCAACTGTCTGTGCGCTATGCCT。
3、取步骤2得到的PCR扩增产物,用限制性内切酶Xba I和Hind III进行双酶切,回收酶切产物。
4、取pACYC184质粒,用限制性内切酶Xba I和Hind III进行双酶切,回收载体骨架(约4.1kb)。
5、将步骤3的酶切产物和步骤4的载体骨架连接,得到重组质粒pACYC184-Pthr-trc。
二、构建各个重组质粒以及相应的重组菌
1、构建重组菌GFP3227
(1)以大肠杆菌K12MG1655的基因组DNA为模板,采用WY3227和WY3254组成的引物对进行PCR扩增,得到PCR扩增产物A1;以pGFPuv载体为模板,采用WY3105和WY1859组成的引物对进行PCR扩增,得到PCR扩增产物A2;将PCR扩增产物A1和PCR扩增产物A2混合后作为模板,采用WY3227和WY1859组成的引物对进行PCR扩增,得到PCR扩增产物A3。
WY3227:CCCAAGCTTAAGATGCAAGAAAAGACAAAatgACAG;
WY3254:AGTTCTTCTCCTTTACTCATAGAACCAGAACCAGAACCTGAGAAACAGAATTTTGTGCT;
WY3105:GGTTCTGGTTCTGGTTCTATGAGTAAAGGAGAAGAACTTTTCA;
引物中,下划线标注的为酶切识别序列,方框标注的为终止子序列。
(2)取步骤(1)得到的PCR扩增产物A3,用限制性内切酶Hind III和Sph I双酶切,回收酶切产物。
(3)取重组质粒pACYC184-Pthr-trc,用限制性内切酶Hind III和Sph I双酶切,回收载体骨架。
(4)将步骤(2)的酶切产物和步骤(3)的载体骨架连接,然后化转至大肠杆菌EC135,并从转化子中提取质粒,得到重组质粒pACYC184-Pthr-trc-ilvLX-gfp3227。根据测序结果,对重组质粒pACYC184-Pthr-trc-ilvLX-gfp3227进行结构描述如下:在质粒pACYC184的Xba I和Sph I酶切位点之间插入了特异DNA分子;特异DNA分子自上游至下游依次由如下元件组成:序列表的序列1所示的启动子Pthr-trc,限制性内切酶Hind III的酶切识别序列,ilvL基因的RBS序列“AAGATGCAAGAAAAGACAAA”,序列表的序列2第1至215位核苷酸(包含完整的ilv衰减子序列和ilvX基因开放阅读框中编码前10个氨基酸残基的核苷酸序列),连接序列“GGTTCTGGTTCTGGTTCT”,序列表的序列3所示的gfp基因,终止子序列CTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTG。
含有重组质粒pACYC184-Pthr-trc-ilvLX-gfp3227的大肠杆菌EC135命名为重组菌GFP3227。
2、构建重组菌GFP3228
(1)以大肠杆菌K12MG1655的基因组DNA为模板,采用WY3228和WY3254组成的引物对进行PCR扩增,得到PCR扩增产物A1;以pGFPuv载体为模板,采用WY3105和WY1859组成的引物对进行PCR扩增,得到PCR扩增产物A2;将PCR扩增产物A1和PCR扩增产物A2混合后作为模板,采用WY3228和WY1859组成的引物对进行PCR扩增,得到PCR扩增产物A3。
WY3228:CCCAAGCTTAGGTCCGGGGGTTTTTTTTGAC。
(2)取步骤(1)得到的PCR扩增产物A3,用限制性内切酶Hind III和Sph I双酶切,回收酶切产物。
(3)取重组质粒pACYC184-Pthr-trc,用限制性内切酶Hind III和Sph I双酶切,回收载体骨架。
(4)将步骤(2)的酶切产物和步骤(3)的载体骨架连接,然后化转至大肠杆菌EC135,并从转化子中提取质粒,得到重组质粒pACYC184-Pthr-trc-ilvLX-gfp3228。根据测序结果,对重组质粒pACYC184-Pthr-trc-ilvLX-gfp3228进行结构描述如下:在质粒pACYC184的Xba I和Sph I酶切位点之间插入了特异DNA分子;特异DNA分子自上游至下游依次由如下元件组成:序列表的序列1所示的启动子Pthr-trc,限制性内切酶Hind III的酶切识别序列,序列表的序列2第137至215位核苷酸(包含进行截短改造后的ilv衰减子序列和ilvX基因开放阅读框中编码前10个氨基酸残基的核苷酸序列),连接序列“GGTTCTGGTTCTGGTTCT”,序列表的序列3所示的gfp基因,终止子序列CTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTG。
含有重组质粒pACYC184-Pthr-trc-ilvLX-gfp3228的大肠杆菌EC135命名为重组菌GFP3228。
3、构建重组菌GFP3229
(1)以大肠杆菌K12MG1655的基因组DNA为模板,采用WY3229和WY3254组成的引物对进行PCR扩增,得到PCR扩增产物A1;以pGFPuv载体为模板,采用WY3105和WY1859组成的引物对进行PCR扩增,得到PCR扩增产物A2;将PCR扩增产物A1和PCR扩增产物A2混合后作为模板,采用WY3229和WY1859组成的引物对进行PCR扩增,得到PCR扩增产物A3。
WY3229:CCCAAGCTTACATAACCGAGGAGCAGACA。
(2)取步骤(1)得到的PCR扩增产物A3,用限制性内切酶Hind III和Sph I双酶切,回收酶切产物。
(3)取重组质粒pACYC184-Pthr-trc,用限制性内切酶Hind III和Sph I双酶切,回收载体骨架。
(4)将步骤(2)的酶切产物和步骤(3)的载体骨架连接,然后化转至大肠杆菌EC135,并从转化子中提取质粒,得到重组质粒pACYC184-Pthr-trc-ilvLX-gfp3229。根据测序结果,对重组质粒pACYC184-Pthr-trc-ilvLX-gfp3229进行结构描述如下:在质粒pACYC184的Xba I和Sph I酶切位点之间插入了特异DNA分子;特异DNA分子自上游至下游依次由如下元件组成:序列表的序列1所示的启动子Pthr-trc,限制性内切酶Hind III的酶切识别序列,序列表的序列2第166至215位核苷酸(完全删除ilv衰减子,包含ilvX基因开放阅读框中编码前10个氨基酸残基的核苷酸序列),连接序列“GGTTCTGGTTCTGGTTCT”,序列表的序列3所示的gfp基因,终止子序列CTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTG。
含有重组质粒pACYC184-Pthr-trc-ilvLX-gfp3229的大肠杆菌EC135命名为重组菌GFP3229。
4、构建GFP对照
将重组质粒pACYC184-Pthr-trc导入大肠杆菌EC135,得到的重组菌命名为GFP对照。
三、GFP荧光强度分析
试验菌株为:重组菌GFP3227、重组菌GFP3228或重组菌GFP3229。
设置GFP对照作为对照菌株。
1、将试验菌株或对照菌株接种至含34mg/L氯霉素的液体LB培养基中,37℃、220rpm振荡培养过夜。
2、取步骤1得到的菌液,按照1%接种量接种于含34mg/L氯霉素的液体LB培养基中,37℃、220rpm振荡培养12小时。
3、取150μL步骤2得到的菌液,加入黑边透底的96孔板中,使用高通量多功能酶标仪(INFINITE 200PRO型,瑞士TECAN)同时检测细胞密度和GFP荧光信号。检测细胞密度的相关参数设置见表1。检测GFP荧光信号的相关参数设置见表2。
表1
吸光度(Absorbance) | |
波长(Wavelength) | 600nm |
带宽(Bandwidth) | 9nm |
闪光次数(Number of Flashes) | 25 |
建立时间(Settle Time) | 0ms |
表2
荧光顶读(Fluorescence Top Reading) | |
激发波长(Excitation Wavelength) | 400nm |
发射波长(Emission Wavelength) | 510nm |
激发带宽(Excitation Bandwidth) | 9nm |
发射带宽(Emission Bandwidth) | 20nm |
收集(Gain) | 100(Manual,手动) |
闪光次数(Number of Flashes) | 15 |
积分时间(Integration Time) | 20μs |
滞后时间(LagTime) | 0μs |
建立时间(Settle Time) | 0ms |
Z位置(Z-Position) | 20000μm(Manual,手动) |
各个试验菌株的荧光强度值=实测荧光值÷细胞密度-对照菌株的实测荧光值÷对照菌株的细胞密度。设置三次重复试验,相应的平均值和标准差结果见表3。
与重组菌GFP3227(携带完整ilv衰减子)相比,重组菌GFP3228(携带ilv衰减子截短体)的荧光强度值提高了149.0%。与重组菌GFP3229(不携带ilv衰减子)相比,重组菌GFP3228的荧光强度值提高了34.1%。结果表明,位于启动子和目的基因之间的ilv衰减子截短体可以作为调控元件,促进目的基因的表达。
ilv衰减子突变体如序列表的序列2第n1至n2位核苷酸所示;n1为129以上148以下的自然数(n1优选为137),n2为155以上215以下的自然数(n2具体可为155以上185以下的自然数或186以上215以下的自然数,更具体可为155、185或215)。ilv衰减子突变体包括ilv衰减子截短体和ilv衰减子变体(全称为在ilv衰减子截短体下游连接其他核苷酸的变体)。ilv衰减子截短体如序列表的序列2第n1至155位核苷酸所示。ilv衰减子变体如序列表的序列2第n1至n3位核苷酸所示,n3为156以上215以下的自然数(n3具体可为156以上185以下的自然数或185以上215以下的自然数,更具体可为185或215)。
表3
荧光强度 | |
重组菌GFP3227 | 1465.4±165.5 |
重组菌GFP3228 | 3649.3±413.2 |
重组菌GFP3229 | 2721.1±138.4 |
实施例2、制备缬氨酸
一、E.coli K-12MG1655△ilvA的构建
1、以大肠杆菌K12MG1655的基因组DNA为模板,采用WY577和WY578组成的引物对进行PCR扩增,得到DNA片段-甲(ilvA基因上游区域)。
WY577:CGCGGATCCGAAAGTGTACGAAAGCCAGG;
WY578:GCGCTATCAGGCATTTTTCCTATTAACCCCCCAGTTTCGA。
2、以大肠杆菌K12MG1655的基因组DNA为模板,采用WY579和WY580组成的引物对进行PCR扩增,得到DNA片段-乙(ilvA基因下游区域)。
WY579:TCGAAACTGGGGGGTTAATAGGAAAAATGCCTGATAGCGC;
WY580:ATTGCGGCCGCGTGAAGCGGATCTGGCGATT。
3、将DNA片段-甲和DNA片段-乙混合后作为模板,采用WY577和WY580组成的引物对进行PCR扩增,得到DNA片段-丙。
4、取pKOV质粒,用限制性内切酶Bam HI和Not I进行双酶切,回收载体骨架(约5.6kb)。
5、取DNA片段-丙,用限制性内切酶Bam HI和Not I进行双酶切,回收酶切产物。
6、将步骤4得到的载体骨架和步骤5得到的酶切产物连接,得到重组质粒△ilvA。根据测序结果,对重组质粒△ilvA进行结构描述如下:在pKOV质粒的Bam HI和Not I酶切位点之间插入了如下特异DNA分子:自上游至下游依次由序列表的序列4第140-637位核苷酸所示的上游区段和序列表的序列4第2183-2712位核苷酸所示的下游区段组成。ilvA基因如序列表的序列4所示,第638-2182位核苷酸为开放阅读框(编码序列表的序列5所示的IlvA蛋白)。
7、将重组质粒△ilvA导入大肠杆菌K12MG1655,得到ilvA基因敲除的重组菌,命名为E.coli K-12MG1655△ilvA。
ilvA基因敲除的重组菌的鉴定方法:采用WY587和WY588组成的引物对进行PCR扩增,如果得到1344bp扩增产物,初步判断为候选的目标菌;进一步通过测序验证菌株染色体上的ilvA基因的开放阅读框被敲除。
WY587:ATGGCTGTATCCGCTCGCTG;
WY588:ACACCATCGATCAGCAAGGGC。
二、构建重组质粒pACYC184-PJJ
1、合成序列表的序列6所示的双链DNA分子(启动子PJJ)。
2、以步骤1制备的双链DNA分子为模板,采用WY843和WY842组成的引物对进行PCR扩增,得到PCR扩增产物。
WY843:TGCTCTAGACAATTCCGACGTCTAAGAAA;
WY842:CGCGGATCCGGTCAGTGCGTCCTGCTGAT。
3、取步骤2得到的PCR扩增产物,用限制性内切酶Xba I和BamHI进行双酶切,回收酶切产物。
4、取pACYC184质粒,用限制性内切酶Xba I和BamH I进行双酶切,回收载体骨架(约4.1kb)。
5、将步骤3的酶切产物和步骤4的载体骨架连接,得到重组质粒pACYC184-PJJ。
三、重组质粒pACYC184-PJJ-ilvLXGMED构建
WY4047:CGCGGATCC AAGATGCAAGAAAAGACAAA atgACAG;
WY4048:CGCGGATCC AGGTCCGGGGGTTTTTTTTGAC;
WY4049:CGCGGATCC ACATAACCGAGGAGCAGACA;
WY4044:TGACCTGATGTTGCATCATGATAATTTCTCCA;
WY4045:TGGAGAAATTATCATGATGCAACATCAGGTCA;
1、以大肠杆菌BL21(DE3)的基因组DNA为模板,采用WY4047和WY4044组成的引物对进行PCR扩增,得到PCR扩增产物B1。
2、以大肠杆菌BL21(DE3)的基因组DNA为模板,采用WY4048和WY4044组成的引物对进行PCR扩增,得到PCR扩增产物B2。
3、以大肠杆菌BL21(DE3)的基因组DNA为模板,采用WY4049和WY4044组成的引物对进行PCR扩增,得到PCR扩增产物B3。
4、以大肠杆菌K12MG1655的基因组DNA为模板,采用WY4045和WY4046组成的引物对进行PCR扩增,得到PCR扩增产物B4。
5、将PCR扩增产物B1和PCR扩增产物B4混合后作为模板,采用WY4047和WY4046组成的引物对进行PCR扩增,得到PCR扩增产物C1。
6、将PCR扩增产物B2和PCR扩增产物B4混合后作为模板,采用WY4048和WY4046组成的引物对进行PCR扩增,得到PCR扩增产物C2。
7、将PCR扩增产物B3和PCR扩增产物B4混合后作为模板,采用WY4049和WY4046组成的引物对进行PCR扩增,得到PCR扩增产物C3。
8、取质粒pACYC184-PJJ,用限制性内切酶BamH I和Eag I双酶切,回收载体骨架。
9、取PCR扩增产物C1,用限制性内切酶BamH I和Eag I双酶切,回收酶切产物。
10、将步骤8的载体骨架和步骤9的酶切产物连接,得到重组质粒pACYC184-PJJ-ilvL4047XGMED。根据测序结果,对重组质粒pACYC184-PJJ-ilvL4047XGMED进行结构描述如下:在质粒pACYC184的Xba I和Eag I酶切位点之间插入了特异DNA分子;特异DNA分子自上游至下游依次由如下元件组成:序列表的序列6所示的启动子PJJ,限制性内切酶BamH I的酶切识别序列,ilvL基因的RBS序列“AAGATGCAAGAAAAGACAAA”,序列表的序列2所示的双链DNA分子。
11、取PCR扩增产物C2,用限制性内切酶BamH I和Eag I双酶切,回收酶切产物。
12、将步骤8的载体骨架和步骤11的酶切产物连接,得到重组质粒pACYC184-PJJ-ilvL4048XGMED。根据测序结果,对重组质粒pACYC184-PJJ-ilvL4048XGMED进行结构描述如下:在质粒pACYC184的Xba I和Eag I酶切位点之间插入了特异DNA分子;特异DNA分子自上游至下游依次由如下元件组成:序列表的序列6所示的启动子PJJ,限制性内切酶BamH I的酶切识别序列,序列表的序列2第137至5057位核苷酸所示的双链DNA分子。
13、取PCR扩增产物C3,用限制性内切酶BamH I和Eag I双酶切,回收酶切产物。
14、将步骤8的载体骨架和步骤13的酶切产物连接,得到重组质粒pACYC184-PJJ-ilvL4049XGMED。根据测序结果,对重组质粒pACYC184-PJJ-ilvL4049XGMED进行结构描述如下:在质粒pACYC184的Xba I和Eag I酶切位点之间插入了特异DNA分子;特异DNA分子自上游至下游依次由如下元件组成:序列表的序列6所示的启动子PJJ,限制性内切酶BamH I的酶切识别序列,序列表的序列2第166至5057位核苷酸所示的双链DNA分子。
四、构建工程菌
将重组质粒pACYC184-PJJ-ilvL4047XGMED导入E.coli K-12MG1655△ilvA中,得到重组菌,将其命名为工程菌IlvL4047。
将重组质粒pACYC184-PJJ-ilvL4048XGMED导入E.coli K-12MG1655△ilvA中,得到重组菌,将其命名为工程菌IlvL4048。
将重组质粒pACYC184-PJJ-ilvL4049XGMED导入E.coli K-12MG1655△ilvA中,得到重组菌,将其命名为工程菌IlvL4049。
五、缬氨酸工程菌的摇瓶发酵试验
试验菌株为:工程菌IlvL4047、工程菌IlvL4048或工程菌IlvL4049。
1、取试验菌株,划线接种于含34mg/L氯霉素的固体LB培养基平板,37℃静置培养12小时。
2、完成步骤1后,挑取平板上的菌苔,接种至液体LB培养基中,37℃、220rpm振荡培养12h,得到种子液(OD600nm值=5.0)。
3、完成步骤2后,将种子液按照3%的接种量接种至发酵培养基中,37℃、220rpm震荡培养。
发酵培养基:葡萄糖20.0g/L、硫酸铵15.0g/L、磷酸二氢钾2.0g/L、七水硫酸镁2.0g/L、酵母粉2.0g/L、异亮氨酸0.6g/L、碳酸钙15.0g/L、微量元素混合液5mL/L,余量为水。
微量元素混合液:FeSO4·7H2O 10g/L、CaCl2 1.35g/L、ZnSO4·7H2O 2.25g/L、MnSO4·4H2O 0.5g/L、CuSO4·5H2O 1g/L、(NH4)6Mo7O24·4H2O 0.106g/L、Na2B4O7·10H2O0.23g/L、CoCl2·6H2O 0.48g/L、35%HCl 10mL/L,余量为水。
培养过程中,用氨水调节反应体系的pH值使其维持在6.8-7.0。
培养过程中,每隔3-4h取样一次,使用生物传感分析仪SBA-40D检测葡萄糖含量,当体系中的葡萄糖含量低于5g/L时,补加葡萄糖并使体系中的葡萄糖浓度达到10g/L。
培养36h后取样,12000g离心2分钟,取上清液(发酵上清),检测L-缬氨酸浓度。
结果见表4(三次重复试验的平均值±标准差)。工程菌IlvL4048生产L-缬氨酸的能力最高,发酵上清中的L-缬氨酸浓度为2.58±0.55。
表4
发酵上清中的L-缬氨酸含量(g/L) | |
工程菌IlvL4047 | 1.02±0.15 |
工程菌IlvL4048 | 2.58±0.55 |
工程菌IlvL4049 | 1.82±0.22 |
发酵上清中L-缬氨酸浓度的检测方法:高效液相法,在参考文献(氨基酸和生物资源,2000,22,59-60)中氨基酸检测方法的基础上进行优化,具体方法如下(2,4-二硝基氟苯(FDBN)柱前衍生高效液相法):
取10μL上清液于2mL离心管中,加入200μL 0.5M NaHCO3水溶液和100μL 1%(体积比)FDBN-乙腈溶液,于60℃水浴中暗处恒温加热60min,然后冷却至室温,然后加入700μL0.04mol/L KH2PO4水溶液(pH=7.2±0.05,用40g/L KOH水溶液调整pH)并摇匀,静置15min,然后过滤并收集滤液。滤液用于上样,进样量为15μL。
色谱柱为C18柱(ZORBAX Eclipse XDB-C18,4.6*150mm,Agilent,USA);柱温:40℃;紫外检测波长:360nm;流动相A为0.04mol/L KH2PO4水溶液(pH=7.2±0.05,用40g/100mL KOH水溶液调整pH),流动相B为55%(体积比)乙腈水溶液,流动相总流量为1mL/min。
洗脱过程:洗脱起始时刻(0min)流动相A占流动相总流量的体积份数为86%、流动相B占流动相总流量的体积份数为14%;洗脱过程分为4个阶段,每个阶段中流动相A和流动相B占流动相总流量的体积份数均为线性变化;第1阶段(从起始时刻开始共进行2min)结束时流动相A占流动相总流量的体积份数为88%、流动相B占流动相总流量的体积份数为12%,第2阶段(从第1阶段结束时刻开始共进行2min)结束时流动相A占流动相总流量的体积份数为86%、流动相B占流动相总流量的体积份数为14%,第3阶段(从第2阶段结束时刻开始共进行6min)结束时流动相A占流动相总流量的体积份数为70%、流动相B占流动相总流量的体积份数为30%,第4阶段(从第3阶段结束时刻开始共进行10min)结束时流动相A占流动相总流量的体积份数为30%、流动相B占流动相总流量的体积份数为70%。
以市售L-缬氨酸为标准品制作标准曲线,计算样品的缬氨酸浓度。
最后应说明的是:显然,上述实施例仅仅是为清楚地说明本发明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引申出的显而易见的变化或变动仍处于本发明的保护范围之中。
SEQUENCE LISTING
<110> 中国科学院微生物研究所
<120> ilv衰减子的突变体、相关工程菌及其在生产缬氨酸中的应用
<130> GNCYX171070
<160> 11
<170> PatentIn version 3.5
<210> 1
<211> 192
<212> DNA
<213> 大肠杆菌
<400> 1
gcttttcatt ctgactgcaa cgggcaatat gtctctgtgt ggattaaaaa aagagtgtct 60
gatagcagct tctgaactgg ttacctgccg tgagtaaatt aaaattttat tgacttaggt 120
cactaaatac tttaaccaat ataggcatag cgcacagaca gttgacaatt aatcatccgg 180
ctcgtataat gt 192
<210> 2
<211> 5057
<212> DNA
<213> 人工序列
<400> 2
atgacagccc ttctacgagt gattagcctg gtcgtgatta gcgtggtggt gattattatc 60
ccaccgtgcg gggctgcact tggacgagga aaggcttaga gatcaagcct taacgaacta 120
agacccccgc accgaaaggt ccgggggttt tttttgacct taaaaacata accgaggagc 180
agacaatgaa taacagcaca aaattctgtt tctcaagatt caggacgggg aactaactat 240
gaatggcgca cagtgggtgg tacatgcgtt gcgggcacag ggtgtgaaca ccgttttcgg 300
ttatccgggt ggcgcaatta tgccggttta cgatgcattg tatgacggcg gcgtggagca 360
cttgctatgc cgacatgagc agggtgcggc aatggcggct atcggttatg ctcgtgctac 420
cggcaaaact ggcgtatgta tcgccacgtc tggtccgggc gcaaccaacc tgataaccgg 480
gcttgcggac gcactgttag attccatccc tgttgttgcc atcaccggtc aagtgtccgc 540
accgtttatc ggcactgacg catttcagga agtggatgtc ctgggattgt cgttagcctg 600
taccaagcac agctttctgg tgcagtcgct ggaagagttg ccgcgcatca tggctgaagc 660
attcgacgtt gcctgctcag gtcgtcctgg tccggttctg gtcgatatcc caaaagatat 720
ccagttagcc agcggtgacc tggaaccgtg gttcaccacc gttgaaaacg aagtgacttt 780
cccacatgcc gaagttgagc aagcgcgcca gatgctggca aaagcgcaaa aaccgatgct 840
gtacgttggc ggtggcgtgg gtatggcgca ggcagttccg gctttgcgtg aatttctcgc 900
tgccacaaaa atgcctgcca cctgtacgct gaaagggctg ggcgcagtag aagcagatta 960
tccgtactat ctgggcatgc tgggaatgca tggcaccaaa gcggcgaact tcgcggtgca 1020
ggagtgcgac ttgctgatcg ccgtgggtgc acgttttgat gaccgggtga ccggcaaact 1080
gaacaccttc gcaccacacg ccagtgttat ccatatggat atcgacccgg cagaaatgaa 1140
caagctgcgt caggcacatg tggcattaca aggtgattta aatgctctgt taccagcatt 1200
acagcagccg ttaaatatca atgactggca gctacactgc gcgcagctgc gtgatgaaca 1260
tgcctggcgt tacgaccatc ccggtgacgc tatctacgcg ccgttgttgt taaaacaact 1320
gtcagatcgt aaacctgcgg attgcgtcgt gaccacagat gtggggcagc accagatgtg 1380
ggctgcgcag cacatcgccc acactcgccc ggaaaatttc atcacctcca gcggcttagg 1440
caccatgggt tttggtttac cggcggcggt tggcgcgcaa gtcgcgcgac caaacgatac 1500
cgtcgtctgt atctccggtg acggctcttt catgatgaat gtgcaagagc tgggcaccgt 1560
aaaacgcaag cagttaccgt tgaaaatcgt cttactcgat aaccaacggt tagggatggt 1620
tcgacaatgg cagcaactgt ttttccagga acgatatagc gaaaccaccc ttaccgataa 1680
ccccgatttc ctcatgttag ccagcgcctt cggcatccct ggccaacaca tcacccgtaa 1740
agaccaggtt gaagcggcac tcgacaccat gctgaacagt gatgggccat acctgcttca 1800
tgtctcaatc gacgaacttg agaacgtctg gccgctggtg ccgcctggtg ccagtaattc 1860
agaaatgttg gagaaattat catgatgcaa catcaggtca atgtatcggc tcgcttcaat 1920
ccagaaacct tagaacgtgt tttacgcgtg gtgcgtcatc gtggtttcca cgtctgctca 1980
atgaatatgg ccgccgccag cgatgcacaa aatataaata tcgaattgac cgttgccagc 2040
ccacggtcgg tcgacttact gtttagtcag ttaaataaac tggtggacgt cgcacacgtt 2100
gccatctgcc agagcacaac cacatcacaa caaatccgcg cctgagcgca aaaggaatat 2160
aaaaatgacc acgaagaaag ctgattacat ttggttcaat ggggagatgg ttcgctggga 2220
agacgcgaag gtgcatgtga tgtcgcacgc gctgcactat ggcacttcgg tttttgaagg 2280
catccgttgc tacgactcgc acaaaggacc ggttgtattc cgccatcgtg agcatatgca 2340
gcgtctgcat gactccgcca aaatctatcg cttcccggtt tcgcagagca ttgatgagct 2400
gatggaagct tgtcgtgacg tgatccgcaa aaacaatctc accagcgcct atatccgtcc 2460
gctgatcttc gtcggtgatg ttggcatggg agtaaacccg ccagcgggat actcaaccga 2520
cgtgattatc gctgctttcc cgtggggagc gtatctgggc gcagaagcgc tggagcaggg 2580
gatcgatgcg atggtttcct cctggaaccg cgcagcacca aacaccatcc cgacggcggc 2640
aaaagccggt ggtaactacc tctcttccct gctggtgggt agcgaagcgc gccgccacgg 2700
ttatcaggaa ggtatcgcgc tggatgtgaa cggttatatc tctgaaggcg caggcgaaaa 2760
cctgtttgaa gtgaaagatg gtgtgctgtt caccccaccg ttcacctcct ccgcgctgcc 2820
gggtattacc cgtgatgcca tcatcaaact ggcgaaagag ctgggaattg aagtacgtga 2880
gcaggtgctg tcgcgcgaat ccctgtacct ggcggatgaa gtgtttatgt ccggtacggc 2940
ggcagaaatc acgccagtgc gcagcgtaga cggtattcag gttggcgaag gccgttgtgg 3000
cccggttacc aaacgcattc agcaagcctt cttcggcctc ttcactggcg aaaccgaaga 3060
taaatggggc tggttagatc aagttaatca ataaatacaa aaaatgggac ggcacgcacc 3120
gtcccattta cgagacagac actgggagta aataaagtat gcctaagtac cgttccgcca 3180
ccaccactca tggtcgtaat atggcgggtg ctcgtgcgct gtggcgcgcc accggaatga 3240
ccgacgccga tttcggtaag ccgattatcg cggttgtgaa ctcgttcacc caatttgtac 3300
cgggtcacgt ccatctgcgc gatctcggta aactggtcgc cgaacaaatt gaagcggctg 3360
gcggcgttgc caaagagttc aacaccattg cggtggatga tgggattgcc atgggccacg 3420
gggggatgct ttattcactg ccatctcgcg aactgatcgc tgattccgtt gagtatatgg 3480
tcaacgccca ctgcgccgac gccatggtct gcatctctaa ctgcgacaaa atcaccccgg 3540
ggatgctgat ggcttccctg cgcctgaata ttccggtgat ctttgtttcc ggcggcccga 3600
tggaggccgg gaaaaccaaa ctttccgatc agatcatcaa gctcgatctg gttgatgcga 3660
tgatccaggg cgcagacccg aaagtatctg actcccagag cgatcaggtt gaacgttccg 3720
cgtgtccgac ctgcggttcc tgctccggga tgtttaccgc taactcaatg aactgcctga 3780
ccgaagcgct gggcctgtcg cagccgggca acggctcgct gctggcaacc cacgccgacc 3840
gtaagcagct gttccttaat gctggtaaac gcattgttga attgaccaaa cgttattacg 3900
agcaaaacga cgaaagtgca ctgccgcgta atatcgccag taaggcggcg tttgaaaacg 3960
ccatgacgct ggatatcgcg atgggtggat cgactaacac cgtacttcac ctgctggcgg 4020
cggcgcagga agcggaaatc gacttcacca tgagtgatat cgataagctt tcccgcaagg 4080
ttccacagct gtgtaaagtt gcgccgagca cccagaaata ccatatggaa gatgttcacc 4140
gtgctggtgg tgttatcggt attctcggcg aactggatcg cgcggggtta ctgaaccgtg 4200
atgtgaaaaa cgtacttggc ctgacgttgc cgcaaacgct ggaacaatac gacgttatgc 4260
tgacccagga tgacgcggta aaaaatatgt tccgcgcagg tcctgcaggc attcgtacca 4320
cacaggcatt ctcgcaagat tgccgttggg atacgctgga cgacgatcgc gccaatggct 4380
gtatccgctc gctggaacac gcctacagca aagacggcgg cctggcggtg ctctacggta 4440
actttgcgga aaacggctgc atcgtgaaaa cggcaggcgt cgatgacagc atcctcaaat 4500
tcaccggccc ggcgaaagtg tacgaaagcc aggacgatgc ggtagaagcg attctcggcg 4560
gtaaagttgt cgccggagat gtggtagtaa ttcgctatga aggcccgaaa ggcggtccgg 4620
ggatgcagga aatgctctac ccaaccagct tcctgaaatc aatgggtctc ggcaaagcct 4680
gtgcgctgat caccgacggt cgtttctctg gtggcacctc tggtctttcc atcggccacg 4740
tctcaccgga agcggcaagc ggcggcagca ttggcctgat tgaagatggt gacctgatcg 4800
ctatcgacat cccgaaccgt ggcattcagt tacaggtaag cgatgccgaa ctggcggcgc 4860
gtcgtgaagc gcaggacgct cgaggtgaca aagcctggac gccgaaaaat cgtgaacgtc 4920
aggtctcctt tgccctgcgt gcttatgcca gcctggcaac cagcgccgac aaaggcgcgg 4980
tgcgcgataa atcgaaactg gggggttaac tagcataacc ccttggggcc tctaaacggg 5040
tcttgagggg ttttttg 5057
<210> 3
<211> 717
<212> DNA
<213> 人工序列
<400> 3
atgagtaaag gagaagaact tttcactgga gttgtcccaa ttcttgttga attagatggt 60
gatgttaatg ggcacaaatt ttctgtcagt ggagagggtg aaggtgatgc aacatacgga 120
aaacttaccc ttaaatttat ttgcactact ggaaaactac ctgttccatg gccaacactt 180
gtcactactt tctcttatgg tgttcaatgc ttttcccgtt atccggatca tatgaaacgg 240
catgactttt tcaagagtgc catgcccgaa ggttatgtac aggaacgcac tatatctttc 300
aaagatgacg ggaactacaa gacgcgtgct gaagtcaagt ttgaaggtga tacccttgtt 360
aatcgtatcg agttaaaagg tattgatttt aaagaagatg gaaacattct cggacacaaa 420
ctcgagtaca actataactc acacaatgta tacatcacgg cagacaaaca aaagaatgga 480
atcaaagcta acttcaaaat tcgccacaac attgaagatg gatccgttca actagcagac 540
cattatcaac aaaatactcc aattggcgat ggccctgtcc ttttaccaga caaccattac 600
ctgtcgacac aatctgccct ttcgaaagat cccaacgaaa agcgtgacca catggtcctt 660
cttgagtttg taactgctgc tgggattaca catggcatgg atgagctcta caaataa 717
<210> 4
<211> 2889
<212> DNA
<213> 大肠杆菌
<400> 4
atggctgtat ccgctcgctg gaacacgcct acagcaaaga cggcggcctg gcggtgctct 60
acggtaactt tgcggaaaac ggctgcatcg tgaaaacggc aggcgtcgat gacagcatcc 120
tcaaattcac cggcccggcg aaagtgtacg aaagccagga cgatgcggta gaagcgattc 180
tcggcggtaa agttgtcgcc ggagatgtgg tagtaattcg ctatgaaggc ccgaaaggcg 240
gtccggggat gcaggaaatg ctctacccaa ccagcttcct gaaatcaatg ggtctcggca 300
aagcctgtgc gctgatcacc gacggtcgtt tctctggtgg cacctctggt ctttccatcg 360
gccacgtctc accggaagcg gcaagcggcg gcagcattgg cctgattgaa gatggtgacc 420
tgatcgctat cgacatcccg aaccgtggca ttcagttaca ggtaagcgat gccgaactgg 480
cggcgcgtcg tgaagcgcag gacgctcgag gtgacaaagc ctggacgccg aaaaatcgtg 540
aacgtcaggt ctcctttgcc ctgcgtgctt atgccagcct ggcaaccagc gccgacaaag 600
gcgcggtgcg cgataaatcg aaactggggg gttaataatg gctgactcgc aacccctgtc 660
cggtgctccg gaaggtgccg aatatttaag agcagtgctg cgcgcgccgg tttacgaggc 720
ggcgcaggtt acgccgctac aaaaaatgga aaaactgtcg tcgcgtcttg ataacgtcat 780
tctggtgaag cgcgaagatc gccagccagt gcacagcttt aagctgcgcg gcgcatacgc 840
catgatggcg ggcctgacgg aagaacagaa agcgcacggc gtgatcactg cttctgcggg 900
taaccacgcg cagggcgtcg cgttttcttc tgcgcggtta ggcgtgaagg ccctgatcgt 960
tatgccaacc gccaccgccg acatcaaagt cgacgcggtg cgcggcttcg gcggcgaagt 1020
gctgctccac ggcgcgaact ttgatgaagc gaaagccaaa gcgatcgaac tgtcacagca 1080
gcaggggttc acctgggtgc cgccgttcga ccatccgatg gtgattgccg ggcaaggcac 1140
gctggcgctg gaactgctcc agcaggacgc ccatctcgac cgcgtatttg tgccagtcgg 1200
cggcggcggt ctggctgctg gcgtggcggt gctgatcaaa caactgatgc cgcaaatcaa 1260
agtgatcgcc gtagaagcgg aagactccgc ctgcctgaaa gcagcgctgg atgcgggtca 1320
tccggttgat ctgccgcgcg tagggctatt tgctgaaggc gtagcggtaa aacgcatcgg 1380
tgacgaaacc ttccgtttat gccaggagta tctcgacgac atcatcaccg tcgatagcga 1440
tgcgatctgt gcggcgatga aggatttatt cgaagatgtg cgcgcggtgg cggaaccctc 1500
tggcgcgctg gcgctggcgg gaatgaaaaa atatatcgcc ctgcacaaca ttcgcggcga 1560
acggctggcg catattcttt ccggtgccaa cgtgaacttc cacggcctgc gctacgtctc 1620
agaacgctgc gaactgggcg aacagcgtga agcgttgttg gcggtgacca ttccggaaga 1680
aaaaggcagc ttcctcaaat tctgccaact gcttggcggg cgttcggtca ccgagttcaa 1740
ctaccgtttt gccgatgcca aaaacgcctg catctttgtc ggtgtgcgcc tgagccgcgg 1800
cctcgaagag cgcaaagaaa ttttgcagat gctcaacgac ggcggctaca gcgtggttga 1860
tctctccgac gacgaaatgg cgaagctaca cgtgcgctat atggtcggcg gacgtccatc 1920
gcatccgttg caggaacgcc tctacagctt cgaattcccg gaatcaccgg gcgcgctgct 1980
gcgcttcctc aacacgctgg gtacgtactg gaacatttct ttgttccact atcgcagcca 2040
tggcaccgac tacgggcgcg tactggcggc gttcgaactt ggcgaccatg aaccggattt 2100
cgaaacccgg ctgaatgagc tgggctacga ttgccacgac gaaaccaata acccggcgtt 2160
caggttcttt ttggcgggtt agggaaaaat gcctgatagc gcttcgctta tcaggcctac 2220
ccgcgcgaca acgtcatttg tggttcggca aaatcttcca gaatgcctca attagcggct 2280
catgtagccg ctttttctgc gcacacacgc ccagctcaaa cggcgttttc tcatcgctgc 2340
gctctaaaat catcacgcgg ttacgcaccg gttcggggct gttttccagc accacttccg 2400
gcaacaatgc cacgccacag ccgagtgcca ccatcgatac catcgcttca tgcccgccaa 2460
ccgtggcgta aatcatcggg ttactgattt tattgcgtcg aaaccacagt tcaatgcggc 2520
ggcgtaccgg cccctgatcg gccataataa acggcaccgt tgaccagtcc ggcttctcta 2580
ccgacacctg attacgcacc gggcagggca gcgcgggggc aatcagcact actgccagat 2640
tctccagcat cgaaaacgcc actgcgccgg gcaaggtttc cggtttaccc gcaatcgcca 2700
gatccgcttc accagtgacc accttttcca tcgcatctgc cgcatcacca gtagtaagtt 2760
taatctccac cgacgggtgt tccgcgcgga agcgatccag aatcggcggc agatggctgt 2820
aggcagcggt caccgagcag aagatatgta attcgccaga gagcgacggc ccttgctgat 2880
cgatggtgt 2889
<210> 5
<211> 514
<212> PRT
<213> 大肠杆菌
<400> 5
Met Ala Asp Ser Gln Pro Leu Ser Gly Ala Pro Glu Gly Ala Glu Tyr
1 5 10 15
Leu Arg Ala Val Leu Arg Ala Pro Val Tyr Glu Ala Ala Gln Val Thr
20 25 30
Pro Leu Gln Lys Met Glu Lys Leu Ser Ser Arg Leu Asp Asn Val Ile
35 40 45
Leu Val Lys Arg Glu Asp Arg Gln Pro Val His Ser Phe Lys Leu Arg
50 55 60
Gly Ala Tyr Ala Met Met Ala Gly Leu Thr Glu Glu Gln Lys Ala His
65 70 75 80
Gly Val Ile Thr Ala Ser Ala Gly Asn His Ala Gln Gly Val Ala Phe
85 90 95
Ser Ser Ala Arg Leu Gly Val Lys Ala Leu Ile Val Met Pro Thr Ala
100 105 110
Thr Ala Asp Ile Lys Val Asp Ala Val Arg Gly Phe Gly Gly Glu Val
115 120 125
Leu Leu His Gly Ala Asn Phe Asp Glu Ala Lys Ala Lys Ala Ile Glu
130 135 140
Leu Ser Gln Gln Gln Gly Phe Thr Trp Val Pro Pro Phe Asp His Pro
145 150 155 160
Met Val Ile Ala Gly Gln Gly Thr Leu Ala Leu Glu Leu Leu Gln Gln
165 170 175
Asp Ala His Leu Asp Arg Val Phe Val Pro Val Gly Gly Gly Gly Leu
180 185 190
Ala Ala Gly Val Ala Val Leu Ile Lys Gln Leu Met Pro Gln Ile Lys
195 200 205
Val Ile Ala Val Glu Ala Glu Asp Ser Ala Cys Leu Lys Ala Ala Leu
210 215 220
Asp Ala Gly His Pro Val Asp Leu Pro Arg Val Gly Leu Phe Ala Glu
225 230 235 240
Gly Val Ala Val Lys Arg Ile Gly Asp Glu Thr Phe Arg Leu Cys Gln
245 250 255
Glu Tyr Leu Asp Asp Ile Ile Thr Val Asp Ser Asp Ala Ile Cys Ala
260 265 270
Ala Met Lys Asp Leu Phe Glu Asp Val Arg Ala Val Ala Glu Pro Ser
275 280 285
Gly Ala Leu Ala Leu Ala Gly Met Lys Lys Tyr Ile Ala Leu His Asn
290 295 300
Ile Arg Gly Glu Arg Leu Ala His Ile Leu Ser Gly Ala Asn Val Asn
305 310 315 320
Phe His Gly Leu Arg Tyr Val Ser Glu Arg Cys Glu Leu Gly Glu Gln
325 330 335
Arg Glu Ala Leu Leu Ala Val Thr Ile Pro Glu Glu Lys Gly Ser Phe
340 345 350
Leu Lys Phe Cys Gln Leu Leu Gly Gly Arg Ser Val Thr Glu Phe Asn
355 360 365
Tyr Arg Phe Ala Asp Ala Lys Asn Ala Cys Ile Phe Val Gly Val Arg
370 375 380
Leu Ser Arg Gly Leu Glu Glu Arg Lys Glu Ile Leu Gln Met Leu Asn
385 390 395 400
Asp Gly Gly Tyr Ser Val Val Asp Leu Ser Asp Asp Glu Met Ala Lys
405 410 415
Leu His Val Arg Tyr Met Val Gly Gly Arg Pro Ser His Pro Leu Gln
420 425 430
Glu Arg Leu Tyr Ser Phe Glu Phe Pro Glu Ser Pro Gly Ala Leu Leu
435 440 445
Arg Phe Leu Asn Thr Leu Gly Thr Tyr Trp Asn Ile Ser Leu Phe His
450 455 460
Tyr Arg Ser His Gly Thr Asp Tyr Gly Arg Val Leu Ala Ala Phe Glu
465 470 475 480
Leu Gly Asp His Glu Pro Asp Phe Glu Thr Arg Leu Asn Glu Leu Gly
485 490 495
Tyr Asp Cys His Asp Glu Thr Asn Asn Pro Ala Phe Arg Phe Phe Leu
500 505 510
Ala Gly
<210> 6
<211> 162
<212> DNA
<213> 人工序列
<400> 6
caattccgac gtctaagaaa ccattattat catgacatta acctataaaa ataggcgtat 60
cacgaggccc tttcgtcttc acctcgagtc cctatcagtg atagagattg acctccctat 120
cagtgataga gatactgagc acatcagcag gacgcactga cc 162
<210> 7
<211> 16
<212> PRT
<213> 大肠杆菌
<400> 7
Met Asn Asn Ser Thr Lys Phe Cys Phe Ser Arg Phe Arg Thr Gly Asn
1 5 10 15
<210> 8
<211> 548
<212> PRT
<213> 大肠杆菌
<400> 8
Met Asn Gly Ala Gln Trp Val Val His Ala Leu Arg Ala Gln Gly Val
1 5 10 15
Asn Thr Val Phe Gly Tyr Pro Gly Gly Ala Ile Met Pro Val Tyr Asp
20 25 30
Ala Leu Tyr Asp Gly Gly Val Glu His Leu Leu Cys Arg His Glu Gln
35 40 45
Gly Ala Ala Met Ala Ala Ile Gly Tyr Ala Arg Ala Thr Gly Lys Thr
50 55 60
Gly Val Cys Ile Ala Thr Ser Gly Pro Gly Ala Thr Asn Leu Ile Thr
65 70 75 80
Gly Leu Ala Asp Ala Leu Leu Asp Ser Ile Pro Val Val Ala Ile Thr
85 90 95
Gly Gln Val Ser Ala Pro Phe Ile Gly Thr Asp Ala Phe Gln Glu Val
100 105 110
Asp Val Leu Gly Leu Ser Leu Ala Cys Thr Lys His Ser Phe Leu Val
115 120 125
Gln Ser Leu Glu Glu Leu Pro Arg Ile Met Ala Glu Ala Phe Asp Val
130 135 140
Ala Cys Ser Gly Arg Pro Gly Pro Val Leu Val Asp Ile Pro Lys Asp
145 150 155 160
Ile Gln Leu Ala Ser Gly Asp Leu Glu Pro Trp Phe Thr Thr Val Glu
165 170 175
Asn Glu Val Thr Phe Pro His Ala Glu Val Glu Gln Ala Arg Gln Met
180 185 190
Leu Ala Lys Ala Gln Lys Pro Met Leu Tyr Val Gly Gly Gly Val Gly
195 200 205
Met Ala Gln Ala Val Pro Ala Leu Arg Glu Phe Leu Ala Ala Thr Lys
210 215 220
Met Pro Ala Thr Cys Thr Leu Lys Gly Leu Gly Ala Val Glu Ala Asp
225 230 235 240
Tyr Pro Tyr Tyr Leu Gly Met Leu Gly Met His Gly Thr Lys Ala Ala
245 250 255
Asn Phe Ala Val Gln Glu Cys Asp Leu Leu Ile Ala Val Gly Ala Arg
260 265 270
Phe Asp Asp Arg Val Thr Gly Lys Leu Asn Thr Phe Ala Pro His Ala
275 280 285
Ser Val Ile His Met Asp Ile Asp Pro Ala Glu Met Asn Lys Leu Arg
290 295 300
Gln Ala His Val Ala Leu Gln Gly Asp Leu Asn Ala Leu Leu Pro Ala
305 310 315 320
Leu Gln Gln Pro Leu Asn Ile Asn Asp Trp Gln Leu His Cys Ala Gln
325 330 335
Leu Arg Asp Glu His Ala Trp Arg Tyr Asp His Pro Gly Asp Ala Ile
340 345 350
Tyr Ala Pro Leu Leu Leu Lys Gln Leu Ser Asp Arg Lys Pro Ala Asp
355 360 365
Cys Val Val Thr Thr Asp Val Gly Gln His Gln Met Trp Ala Ala Gln
370 375 380
His Ile Ala His Thr Arg Pro Glu Asn Phe Ile Thr Ser Ser Gly Leu
385 390 395 400
Gly Thr Met Gly Phe Gly Leu Pro Ala Ala Val Gly Ala Gln Val Ala
405 410 415
Arg Pro Asn Asp Thr Val Val Cys Ile Ser Gly Asp Gly Ser Phe Met
420 425 430
Met Asn Val Gln Glu Leu Gly Thr Val Lys Arg Lys Gln Leu Pro Leu
435 440 445
Lys Ile Val Leu Leu Asp Asn Gln Arg Leu Gly Met Val Arg Gln Trp
450 455 460
Gln Gln Leu Phe Phe Gln Glu Arg Tyr Ser Glu Thr Thr Leu Thr Asp
465 470 475 480
Asn Pro Asp Phe Leu Met Leu Ala Ser Ala Phe Gly Ile Pro Gly Gln
485 490 495
His Ile Thr Arg Lys Asp Gln Val Glu Ala Ala Leu Asp Thr Met Leu
500 505 510
Asn Ser Asp Gly Pro Tyr Leu Leu His Val Ser Ile Asp Glu Leu Glu
515 520 525
Asn Val Trp Pro Leu Val Pro Pro Gly Ala Ser Asn Ser Glu Met Leu
530 535 540
Glu Lys Leu Ser
545
<210> 9
<211> 87
<212> PRT
<213> 大肠杆菌
<400> 9
Met Met Gln His Gln Val Asn Val Ser Ala Arg Phe Asn Pro Glu Thr
1 5 10 15
Leu Glu Arg Val Leu Arg Val Val Arg His Arg Gly Phe His Val Cys
20 25 30
Ser Met Asn Met Ala Ala Ala Ser Asp Ala Gln Asn Ile Asn Ile Glu
35 40 45
Leu Thr Val Ala Ser Pro Arg Ser Val Asp Leu Leu Phe Ser Gln Leu
50 55 60
Asn Lys Leu Val Asp Val Ala His Val Ala Ile Cys Gln Ser Thr Thr
65 70 75 80
Thr Ser Gln Gln Ile Arg Ala
85
<210> 10
<211> 309
<212> PRT
<213> 大肠杆菌
<400> 10
Met Thr Thr Lys Lys Ala Asp Tyr Ile Trp Phe Asn Gly Glu Met Val
1 5 10 15
Arg Trp Glu Asp Ala Lys Val His Val Met Ser His Ala Leu His Tyr
20 25 30
Gly Thr Ser Val Phe Glu Gly Ile Arg Cys Tyr Asp Ser His Lys Gly
35 40 45
Pro Val Val Phe Arg His Arg Glu His Met Gln Arg Leu His Asp Ser
50 55 60
Ala Lys Ile Tyr Arg Phe Pro Val Ser Gln Ser Ile Asp Glu Leu Met
65 70 75 80
Glu Ala Cys Arg Asp Val Ile Arg Lys Asn Asn Leu Thr Ser Ala Tyr
85 90 95
Ile Arg Pro Leu Ile Phe Val Gly Asp Val Gly Met Gly Val Asn Pro
100 105 110
Pro Ala Gly Tyr Ser Thr Asp Val Ile Ile Ala Ala Phe Pro Trp Gly
115 120 125
Ala Tyr Leu Gly Ala Glu Ala Leu Glu Gln Gly Ile Asp Ala Met Val
130 135 140
Ser Ser Trp Asn Arg Ala Ala Pro Asn Thr Ile Pro Thr Ala Ala Lys
145 150 155 160
Ala Gly Gly Asn Tyr Leu Ser Ser Leu Leu Val Gly Ser Glu Ala Arg
165 170 175
Arg His Gly Tyr Gln Glu Gly Ile Ala Leu Asp Val Asn Gly Tyr Ile
180 185 190
Ser Glu Gly Ala Gly Glu Asn Leu Phe Glu Val Lys Asp Gly Val Leu
195 200 205
Phe Thr Pro Pro Phe Thr Ser Ser Ala Leu Pro Gly Ile Thr Arg Asp
210 215 220
Ala Ile Ile Lys Leu Ala Lys Glu Leu Gly Ile Glu Val Arg Glu Gln
225 230 235 240
Val Leu Ser Arg Glu Ser Leu Tyr Leu Ala Asp Glu Val Phe Met Ser
245 250 255
Gly Thr Ala Ala Glu Ile Thr Pro Val Arg Ser Val Asp Gly Ile Gln
260 265 270
Val Gly Glu Gly Arg Cys Gly Pro Val Thr Lys Arg Ile Gln Gln Ala
275 280 285
Phe Phe Gly Leu Phe Thr Gly Glu Thr Glu Asp Lys Trp Gly Trp Leu
290 295 300
Asp Gln Val Asn Gln
305
<210> 11
<211> 616
<212> PRT
<213> 大肠杆菌
<400> 11
Met Pro Lys Tyr Arg Ser Ala Thr Thr Thr His Gly Arg Asn Met Ala
1 5 10 15
Gly Ala Arg Ala Leu Trp Arg Ala Thr Gly Met Thr Asp Ala Asp Phe
20 25 30
Gly Lys Pro Ile Ile Ala Val Val Asn Ser Phe Thr Gln Phe Val Pro
35 40 45
Gly His Val His Leu Arg Asp Leu Gly Lys Leu Val Ala Glu Gln Ile
50 55 60
Glu Ala Ala Gly Gly Val Ala Lys Glu Phe Asn Thr Ile Ala Val Asp
65 70 75 80
Asp Gly Ile Ala Met Gly His Gly Gly Met Leu Tyr Ser Leu Pro Ser
85 90 95
Arg Glu Leu Ile Ala Asp Ser Val Glu Tyr Met Val Asn Ala His Cys
100 105 110
Ala Asp Ala Met Val Cys Ile Ser Asn Cys Asp Lys Ile Thr Pro Gly
115 120 125
Met Leu Met Ala Ser Leu Arg Leu Asn Ile Pro Val Ile Phe Val Ser
130 135 140
Gly Gly Pro Met Glu Ala Gly Lys Thr Lys Leu Ser Asp Gln Ile Ile
145 150 155 160
Lys Leu Asp Leu Val Asp Ala Met Ile Gln Gly Ala Asp Pro Lys Val
165 170 175
Ser Asp Ser Gln Ser Asp Gln Val Glu Arg Ser Ala Cys Pro Thr Cys
180 185 190
Gly Ser Cys Ser Gly Met Phe Thr Ala Asn Ser Met Asn Cys Leu Thr
195 200 205
Glu Ala Leu Gly Leu Ser Gln Pro Gly Asn Gly Ser Leu Leu Ala Thr
210 215 220
His Ala Asp Arg Lys Gln Leu Phe Leu Asn Ala Gly Lys Arg Ile Val
225 230 235 240
Glu Leu Thr Lys Arg Tyr Tyr Glu Gln Asn Asp Glu Ser Ala Leu Pro
245 250 255
Arg Asn Ile Ala Ser Lys Ala Ala Phe Glu Asn Ala Met Thr Leu Asp
260 265 270
Ile Ala Met Gly Gly Ser Thr Asn Thr Val Leu His Leu Leu Ala Ala
275 280 285
Ala Gln Glu Ala Glu Ile Asp Phe Thr Met Ser Asp Ile Asp Lys Leu
290 295 300
Ser Arg Lys Val Pro Gln Leu Cys Lys Val Ala Pro Ser Thr Gln Lys
305 310 315 320
Tyr His Met Glu Asp Val His Arg Ala Gly Gly Val Ile Gly Ile Leu
325 330 335
Gly Glu Leu Asp Arg Ala Gly Leu Leu Asn Arg Asp Val Lys Asn Val
340 345 350
Leu Gly Leu Thr Leu Pro Gln Thr Leu Glu Gln Tyr Asp Val Met Leu
355 360 365
Thr Gln Asp Asp Ala Val Lys Asn Met Phe Arg Ala Gly Pro Ala Gly
370 375 380
Ile Arg Thr Thr Gln Ala Phe Ser Gln Asp Cys Arg Trp Asp Thr Leu
385 390 395 400
Asp Asp Asp Arg Ala Asn Gly Cys Ile Arg Ser Leu Glu His Ala Tyr
405 410 415
Ser Lys Asp Gly Gly Leu Ala Val Leu Tyr Gly Asn Phe Ala Glu Asn
420 425 430
Gly Cys Ile Val Lys Thr Ala Gly Val Asp Asp Ser Ile Leu Lys Phe
435 440 445
Thr Gly Pro Ala Lys Val Tyr Glu Ser Gln Asp Asp Ala Val Glu Ala
450 455 460
Ile Leu Gly Gly Lys Val Val Ala Gly Asp Val Val Val Ile Arg Tyr
465 470 475 480
Glu Gly Pro Lys Gly Gly Pro Gly Met Gln Glu Met Leu Tyr Pro Thr
485 490 495
Ser Phe Leu Lys Ser Met Gly Leu Gly Lys Ala Cys Ala Leu Ile Thr
500 505 510
Asp Gly Arg Phe Ser Gly Gly Thr Ser Gly Leu Ser Ile Gly His Val
515 520 525
Ser Pro Glu Ala Ala Ser Gly Gly Ser Ile Gly Leu Ile Glu Asp Gly
530 535 540
Asp Leu Ile Ala Ile Asp Ile Pro Asn Arg Gly Ile Gln Leu Gln Val
545 550 555 560
Ser Asp Ala Glu Leu Ala Ala Arg Arg Glu Ala Gln Asp Ala Arg Gly
565 570 575
Asp Lys Ala Trp Thr Pro Lys Asn Arg Glu Arg Gln Val Ser Phe Ala
580 585 590
Leu Arg Ala Tyr Ala Ser Leu Ala Thr Ser Ala Asp Lys Gly Ala Val
595 600 605
Arg Asp Lys Ser Lys Leu Gly Gly
610 615
Claims (10)
1.DNA分子甲,为如下(a1)、(a2)或(a3):
(a1)序列表的序列2第137至215位核苷酸所示的DNA分子;
(a2)在(a1)的末端连接标签序列得到的DNA分子;
(a3)在(a1)的末端连接连接序列得到的DNA分子。
2.权利要求1所述DNA分子甲在促进下游目的基因表达中的应用。
3.DNA分子乙,自上游至下游依次包括:权利要求1所述DNA分子甲和目的基因。
4.DNA分子丙,自上游至下游依次包括:启动子、权利要求1所述DNA分子甲、目的基因和终止子。
5.DNA分子丁,是将ilvLXGMED操纵子基因中从ilv衰减子第1位开始计数的第1至136位核苷酸去除得到的DNA分子;ilvLXGMED操纵子基因如序列表的序列2所示,或者,ilvLXGMED操纵子基因如序列表的序列2第1-5009位核苷酸所示。
6.DNA分子戊,自上游至下游依次包括如下元件:启动子、权利要求5所述DNA分子丁和终止子。
7.含有权利要求5或6所述DNA分子的重组载体或重组菌。
8.权利要求7所述重组菌在制备缬氨酸中的应用。
9.一种提高微生物生产缬氨酸的能力的方法,包括如下步骤:删除微生物的ilvLXGMED操纵子基因中从ilv衰减子第1位开始计数的第1至136位核苷酸;ilvLXGMED操纵子基因如序列表的序列2所示,或者,ilvLXGMED操纵子基因如序列表的序列2第1-5009位核苷酸所示。
10.一种解除微生物中ilvLXGMED操纵子反馈阻遏的方法,包括如下步骤:删除微生物的ilvLXGMED操纵子基因中从ilv衰减子第1位开始计数的第1至136位核苷酸;ilvLXGMED操纵子基因如序列表的序列2所示,或者,ilvLXGMED操纵子基因如序列表的序列2第1-5009位核苷酸所示。
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CN105026550A (zh) * | 2013-03-11 | 2015-11-04 | Cj第一制糖株式会社 | 具有增强的l-缬氨酸生产力的菌株及使用菌株的l-缬氨酸生产方法 |
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CN107058323A (zh) * | 2017-05-27 | 2017-08-18 | 中国科学院微生物研究所 | 基于ilv衰减子的工程菌及其在生产异亮氨酸中的应用 |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105026550A (zh) * | 2013-03-11 | 2015-11-04 | Cj第一制糖株式会社 | 具有增强的l-缬氨酸生产力的菌株及使用菌株的l-缬氨酸生产方法 |
CN106480035A (zh) * | 2016-10-27 | 2017-03-08 | 中国科学院微生物研究所 | 一种5’‑utr元件及其在生产中的应用 |
CN106520801A (zh) * | 2016-10-27 | 2017-03-22 | 中国科学院微生物研究所 | 苏氨酸衰减子的突变体及其应用以及解除苏氨酸操纵子反馈阻遏的方法 |
CN107058323A (zh) * | 2017-05-27 | 2017-08-18 | 中国科学院微生物研究所 | 基于ilv衰减子的工程菌及其在生产异亮氨酸中的应用 |
Non-Patent Citations (1)
Title |
---|
衰减子与基因表达的调控;严锦文;《生物学通报》;19921231;第1、2页 * |
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