CN112980820A - 一种利用sumo融合表达系统制备重组肝素酶i的方法及其所制备的sumo_肝素酶i融合蛋白 - Google Patents
一种利用sumo融合表达系统制备重组肝素酶i的方法及其所制备的sumo_肝素酶i融合蛋白 Download PDFInfo
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- CN112980820A CN112980820A CN202110097126.5A CN202110097126A CN112980820A CN 112980820 A CN112980820 A CN 112980820A CN 202110097126 A CN202110097126 A CN 202110097126A CN 112980820 A CN112980820 A CN 112980820A
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- heparinase
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Abstract
本发明公开了利用SUMO融合表达系统制备重组肝素酶I的方法及其所制备的肝素酶I,该制备方法包括下列步骤:选择来自肝素黄杆菌(Pedobacter heparinus)的肝素酶I序列,其氨基酸序列如SEQIDNo.1所示,共384aa;去除信号肽序列,获得肝素酶I的DNA序列,如SEQIDNo.2;将所述肝素酶I的DNA序列插入带有N端SUMO蛋白标签的pSMART载体质粒;将正确的质粒转化至BL21(DE3)大肠杆菌感受态细胞中,挑取单克隆,通过发酵和纯化获得融合蛋白;用SUMO蛋白酶将SUMO标签蛋白从融合蛋白上切割下来,即获得肝素酶I。本发明的优点是:提高目标蛋白质的可溶性、促进目标蛋白质的正确折叠,避免形成包涵体;降低纯化成本、提高纯化效率;SUMO蛋白标签分子量较小,对肝素酶I的酶活性影响较小,获得纯化的肝素酶I。
Description
本发明涉及生物技术领域,尤其涉及涉及一种利用SUMO融合表达系统制备重组肝素酶I(Heparinase I)的方法。
背景技术
肝素酶主要从一些利用肝素为碳源的细菌中分离得到,最初来源于肝素黄杆菌(Pedobacter heparinus),从肝素黄杆菌中分离纯化出的肝素酶有三种,分别为肝素酶I、肝素酶II、肝素酶III。肝素酶的主要作用是降解肝素,在酶降解法生产低分子肝素和超低分子肝素中有广泛应用。
目前用于低分子肝素生产的肝素酶产品主要有两种来源:一是直接从产肝素酶的微生物中发酵提取(深圳市海普瑞药业股份有限公司,CN102286448B);二是通过基因工程技术构建重组肝素酶工程菌,发酵提取重组肝素酶。
直接从产肝素酶的微生物(如肝素黄杆菌等)中提取肝素酶I,发酵条件和纯化工艺相对复杂,通过菌种选育提高产量的潜力有限。
基因工程重组技术已广泛应用于蛋白质制备,在构建工程菌时,选择合适的蛋白纯化标签,与目标蛋白质形成融合蛋白,可以提高蛋白质的可溶性、屏蔽毒性蛋白、促进蛋白质的正确折叠、增强对高温和蛋白酶的耐受性。目前已有肝素酶I融合蛋白生产工艺,如专利号CN103992995B,名称为一种高表达水溶性肝素酶I融合蛋白及其编码基因
采用基因工程重组技术在大肠杆菌系统中生产肝素酶I等外源蛋白质时面临两个挑战:一是所用蛋白质表达系统的表达水平较低;二是所表达的蛋白质被错误折叠进不溶性的聚集体——包涵体中,提取和复性困难。
而类似谷胱甘肽巯基转移酶标签(GST-Tag)、麦芽糖结合蛋白标签(MBP-Tag)、转录抗终止因子A标签(NusA-Tag)等融合蛋白标签,它们的分子量较大(26-55kDa),会干扰目标蛋白质的正常功能,并且在表达和后续纯化过程中去除标签等环节相对降低了目标蛋白质的产率。
发明内容
为解决现有技术的缺陷和不足,本发明的目的是提供一种利用SUMO融合表达系统制备重组肝素酶I(heparinase I)的方法,以极大地提高目标蛋白质的表达水平、稳定性和可溶性,提高目标蛋白质的活性及产率。
为实现上述目的,本发明的技术方案如下:
根据本发明的一个方面,提供了一种利用SUMO融合表达系统制备重组肝素酶I(heparinase I)的方法,包括下列步骤:
S01:选择来自肝素黄杆菌(Pedobacter heparinus)的肝素酶I序列,其氨基酸序列如SEQIDNo.1所示,共384aa;
S02:去除信号肽序列,获得肝素酶I的DNA序列,如SEQIDNo.2;
S03:将所述肝素酶I的DNA序列插入带有N端SUMO蛋白标签的pSMART载体质粒;
S04:将正确的质粒转化至BL21(DE3)大肠杆菌感受态细胞中,挑取单克隆,经发酵和纯化获得SUMO_肝素酶I融合蛋白;
S05:用SUMO蛋白酶将SUMO标签蛋白从步骤S04所述的SUMO_肝素酶I融合蛋白上切割下来,即获得肝素酶I。
进一步地,还包括融合蛋白的优化步骤。
进一步地,所述融合蛋白的优化条件是融合蛋白在15℃以0.2mmol/l异丙基硫代半乳糖苷(IPTG)诱导表达。
进一步地,还包括融合蛋白的纯化步骤。
进一步地,所述融合蛋白的纯化步骤采用Ni柱亲和层析方法进行分离纯化。
进一步地,所述的SUMO标签蛋白从步骤S04所述的SUMO_肝素酶I融合蛋白上切割下来是包括下列步骤:将所述融合蛋白透析更换缓冲液,加入适量的SUMO蛋白酶,混匀后置于4℃反应过夜,水解后的融合蛋白样本用Ni柱亲和层析方法将带有6个组氨酸片段的SUMO蛋白标签(能结合到Ni柱上)与肝素酶I(不能结合到Ni柱上)分离。
根据本发明的另一个方面,还提供了一种按照上述方法制备的SUMO_肝素酶I融合蛋白,所述融合蛋白的氨基酸序列如SEQIDNo.3。
根据本发明的再一个方面,还提供了一种按照上述方法制备的肝素酶I。
通过本发明的技术方案,利用SUMO融合表达系统制备的重组肝素酶I,融合在目标蛋白质N端的较小的类泛素蛋白修饰物(small ubiquitin-like modifier,SUMO)标签蛋白,分子量大约11kDa,能够极大地提高目标蛋白质的稳定性和可溶性,对目标蛋白质的活性影响较小。并且,SUMO蛋白酶(SUMO Protease)是一种具有较高活性的半胱氨酸蛋白酶,它能识别SUMO标签蛋白的三级结构,而不是氨基酸序列,因此可以高效而且特异性地将SUMO标签蛋白从重组融合蛋白上切割下来,从而获得肝素酶I。
采用SUMO蛋白标签融合表达系统制备重组肝素酶I的优点:
1)提高目标蛋白质的可溶性、促进目标蛋白质的正确折叠,避免形成包涵体;
2)SUMO蛋白标签近N端有6个组氨酸片段,使融合蛋白可以用Ni柱亲和层析方法一步纯化,降低纯化成本、提高纯化效率;
3)SUMO蛋白标签分子量较小,大约11kDa,对肝素酶I的酶活性影响较小,即使不切除融合蛋白中的蛋白标签,也能得到较高活性的肝素酶I;
4)SUMO蛋白酶能识别SUMO标签蛋白的三级结构,可以高效而且特异性地将SUMO标签蛋白从重组融合蛋白上切割下来,从而获得纯化的肝素酶I。
下面结合附图,对本发明的具体实施方式作进一步的详细说明。对于所属技术领域的技术人员而言,从对本发明的详细说明中,本发明的上述和其他的目的、特征和优点将显而易见。
附图说明
图1为本发明一实施例中肝素酶I表达鉴定的SDS-PAGE电泳分析图;
图2为本发明一实施例中肝素酶I表达优化的SDS-PAGE电泳分析图;
图3为本发明一实施例中肝素酶I可溶性分析的SDS-PAGE电泳分析图;
图4为本发明一实施例中肝素酶I包涵体清洗的SDS-PAGE电泳分析图;
图5为本发明一实施例中肝素酶I亲和纯化的SDS-PAGE电泳分析图;
图6为本发明一实施例中肝素酶I免疫印迹Western Blot的SDS-PAGE电泳分析图;
图7为本发明一实施例中肝素酶I去除标签的SDS-PAGE电泳分析图。
具体实施方式
下面通过具体实施方式及实施例并结合附图对本发明作进一步的详细说明。
根据本发明一种典型的实施方式,提供了一种利用SUMO融合表达系统制备重组肝素酶I(Heparinase I)的方法,包括下列步骤:
S01:选择来自肝素黄杆菌(Pedobacter heparinus)的肝素酶I序列,其氨基酸序列如SEQIDNo.1所示,共384aa;
S02:去除信号肽序列,获得肝素酶I的DNA序列,如SEQIDNo.2;
S03:将所述肝素酶I的DNA序列插入带有N端SUMO蛋白标签的pSMART载体质粒;
S04:将正确的质粒转化至BL21(DE3)大肠杆菌感受态细胞中,挑取单克隆,经发酵和纯化获得融合蛋白;
S05:用SUMO蛋白酶将SUMO标签蛋白从步骤S04所述的融合蛋白上切割下来,即获得肝素酶I。
优选的,还包括融合蛋白表达条件的优化步骤。
优选的,所述融合蛋白的优化条件是融合蛋白在15℃以0.2mmol/l异丙基硫代半乳糖苷(IPTG)诱导表达。
优选的,还包括融合蛋白的纯化步骤。
优选的,所述融合蛋白的纯化步骤采用Ni柱亲和层析方法进行分离纯化。
优选的,所述的SUMO标签蛋白从步骤S04所述的SUMO_肝素酶I融合蛋白上切割下来是包括下列步骤:将所述融合蛋白透析更换缓冲液,加入适量的SUMO蛋白酶,混匀后置于4℃反应过夜,水解后的融合蛋白样本用Ni柱亲和层析方法将带有6个组氨酸片段的SUMO蛋白标签(能结合到Ni柱上)与肝素酶I(不能结合到Ni柱上)分离。
根据本发明的一典型实施方式,还提供了按照上述方法制备的SUMO_肝素酶I融合蛋白,所述融合蛋白的氨基酸序列如SEQIDNo.3。
根据本发明的一典型实施方式,还提供了一种按照上述方法制备的肝素酶I。
选择来自肝素黄杆菌(Pedobacter heparinus)的肝素酶I序列,共384aa,其氨基酸序列如SEQIDNo.1所示,发明人经蛋白质序列分析发现,肝素酶I没有跨膜结构,第1-21个氨基酸为信号肽MKKQILYLIVLQQLFLCSAYA,后363个氨基酸为肝素酶I序列。采取大肠杆菌胞内表达方式制备肝素酶I,转入工程菌的序列应预先去除信号肽序列。将肝素酶I的DNA序列如SEQIDNo.2所示,插入带有N端SUMO蛋白标签的pSMART载体质粒。将正确的质粒转化至BL21(DE3)大肠杆菌感受态细胞中,挑取单克隆,经SDS-PAGE验证,融合蛋白表达正常。融合蛋白由109aa的SUMO蛋白标签和363aa的肝素酶I组成,SUMO-肝素酶I融合蛋白的氨基酸序列如SEQIDNo.3所示。
经优化,确定融合蛋白在15℃以0.2mmol/l异丙基硫代半乳糖苷(IPTG)诱导表达最佳。
在融合蛋白靠近N端处设计了6个组氨酸(histidine,H)序列,工程菌发酵液去除上清液,并将菌体破碎后,采用Ni柱亲和层析方法将融合蛋白分离纯化。
将纯化后的融合蛋白样品透析更换缓冲液,加入适量的SUMO蛋白酶,混匀后置于4℃反应过夜。水解后的融合蛋白样本用Ni柱亲和层析方法将带有6个组氨酸片段的SUMO蛋白标签(能结合到Ni柱上)与肝素酶I(不能结合到Ni柱上)分离。
下面将结合实施例进一步说明本发明的有益效果。
实施例一
1.质粒转化至BL21(DE3)感受态细胞中
1.1将质粒2μL加入100μL感受态细菌中,置冰上30min;
1.2 42℃热激90s,迅速置冰中5min;加入500μL LB培养液;
1.3 37℃,220rpm振摇1h,离心后全部涂布于含抗性的LB平板,37℃倒置培养过夜。
2.表达鉴定
2.1挑取5个平板上单克隆接种于含适量抗性的4mL LB培养液的试管中;
2.2 37℃220rpm振摇至菌体OD600为0.6-0.8;
2.3取出1mL培养物,12000g室温离心5min,弃上清,用80μL 1×PBS缓冲液重悬菌体沉淀并加入20μL的5×Loading Buffer;
2.4向剩余的培养物中加入IPTG至终浓度为0.5mM,在37℃220rpm振摇4h,诱导融合蛋白表达;
2.5取出0.5mL培养物,12000g室温离心5min,弃上清,用80μL 1×PBS缓冲液重悬菌体沉淀并加入20μL的5×Loading Buffer。
2.6进行12%SDS-PAGE分析,表达鉴定结果如图1所示,其中M:蛋白质分子量标记(Protein Marker),1:诱导前样品,2:诱导后样品Ⅰ,3:诱导后样品Ⅱ,4:诱导后样品Ⅲ,5:诱导后样品Ⅳ,6:诱导后样品Ⅴ。
3.表达优化
3.1挑取划线平板上单克隆接种于13支含适量抗性的4mL LB培养液的试管中;
3.2 37℃、220rpm振摇至菌体OD600为0.6-0.8;
3.3取出0.4mL培养物,12000g室温离心5min,弃上清,用80μL 1×PBS缓冲液重悬菌体沉淀加入20μL的5×Loading Buffer;
3.4向剩余的培养物中加入IPTG至终浓度分别为0.2mM与1mM,分别在37℃和15℃220rpm振摇4h和16h,诱导融合蛋白表达;
3.5取出0.2mL培养物,12000g室温离心5min,弃上清,用80μL 1×PBS缓冲液重悬菌体沉淀加入20μL的5×Loading Buffer。
3.6进行SDS-PAGE分析,表达优化结果如图2所示,其中
M:蛋白质分子量标记(Protein Marker);
1:未诱导样品;
2-4:37℃、1.0mM IPTG诱导后样品;
5-7:37℃、0.2mM IPTG诱导后样品;
8-10:15℃、1.0mM IPTG诱导后样品;
11-13:15℃、0.2mM IPTG诱导后样品。
4.可溶性分析
取37℃诱导后菌液和15℃诱导后菌液2mL,12000g室温离心5min,弃上清,用1mL的Buffer A(20mM Tris,300mM NaCl,10%Glycerol,pH8.0)重悬离心后沉淀,超声波破碎(Φ3,15%,2s/8s,10min),上清沉淀分别制样,进行12%SDS-PAGE分析,15℃诱导下,融合蛋白均可溶,可溶性分析结果如图3所示,其中
M:蛋白质分子量标记(Protein Marker);
1:未诱导样品;
2:诱导后样品;
3:37℃、1.0mM IPTG诱后沉淀样;
4:37℃、1.0mM IPTG诱后上清样;
5:37℃、0.2mM IPTG诱后沉淀样;
6:37℃、0.2mM IPTG诱后上清样;
7:15℃、1.0mM IPTG诱后沉淀样;
8:15℃、1.0mM IPTG诱后上清样;
9:15℃、0.2mM IPTG诱后沉淀样;
10:15℃、0.2mM IPTG诱后上清样。
5.放大培养与包涵体清洗
取表达最优克隆菌株37℃扩大培养1L至OD600=0.6~0.8,37℃1.0mM IPTG诱导4h后收菌。40mL Buffer A(20mM Tris,300mM NaCl,10%Glycerol,pH8.0)重悬菌体后超声破碎(Φ10,15%,2s/8s,30min),12000rpm离心15min,上清沉淀分别制样,剩余上清收集保存至4℃。20mL Buffer B(20mM Tris,8M Urea,pH8.0)重悬剩余沉淀后超声破碎(Φ10,15%,2s/8s,30min),12000rpm离心15min,上清沉淀分别制样,剩余上清收集保存至4℃。经12%SDS-PAGE分析,目的蛋白大量存在于Buffer B超声破碎后的上清中,如图4所示,其中
M:蛋白质分子量标记(Protein Marker);
1:破碎后上清样;
2:破碎后沉淀样;
3:破碎后上清样;
4:破碎后沉淀样。
6.Ni柱亲和纯化
取BufferB破碎后上清用2mL Ni柱孵育1.5h后纯化,收集流出液并制样。用BufferC(20mM Tris,8M Urea,10%Glycerol,20mM Imidazole,pH8.0)清洗10CV,收集并制样。最后用Buffer D(20mM Tris,8M Urea,10%Glycerol,500mM Imidazole,pH8.0)洗脱,收集并制样。经SDS-PAGE分析,目的蛋白大部分存在于洗脱样中,亲和纯化结果如图5所示,其中
M:蛋白质分子量标记(Protein Marker);
1:破碎后沉淀样;
2:破碎后上清样;
3:流出样;
4:Buffer C清洗样;
5:Buffer D洗脱样。
7.洗脱样免疫印迹(Western Blot)分析
7.1 SDS-PAGE
电泳样品:预染色的蛋白质分子量标记(Protein Marker),Buffer D洗脱样
电泳条件:200V,60min。
7.2半干式电转印
a.在电泳的正在进行的时候,将PVDF膜切出与凝胶一样大小,并剪去一个小角,帮助判断方向,放置在甲醇中浸泡30s,后转移到电转液中。
b.薄滤纸和厚滤纸切出比凝胶略大一些,各两张,置转移缓冲液浸泡。
c.电泳完成后,将胶的浓缩胶切除,放置在电转液中。按照厚滤纸,薄滤纸,NC膜,胶,薄滤纸,厚滤纸顺序放置在电转仪平面上。
d.每层之间的气泡要全部去除。可以用手轻轻按住一端,再用50mL离心管轻轻在上层往一边移动去除气泡,再将手换一端,离心管往另外一端去除气泡。
e.将电转仪链接到仪器上设置,30V,蛋白小于50KDa,用30mins;蛋白大于50KDa,用45mins。
7.3膜的封闭和抗体孵育及最终处理
a.洗转印膜:室温用1×PBST漂洗5min共3次,在加入任何溶液的时候都不得在膜上加入,沿盒子的角缓慢加入,以免将膜上结合的物质冲掉,摇床转速40rpm。
b.将PBST倒掉,放入5%脱脂奶粉的封闭液内,摇床调到最低转速,室温封闭2h。
c.室温用1×PBST漂洗5min,共3次。
d.加入抗体(1:2000到5%脱脂奶粉中),孵育1h,使用后回收到-20℃。
e.室温用1×PBST漂洗5min,共3次。
f.缓慢加入少量ECL液,能将膜全部覆盖,静置2min后拍照,如图6所示,其中,M:蛋白质分子量标记(Protein Marker),样本(Sample):Buffer D洗脱样。
8.去除标签蛋白
8.1将洗脱样全部透析至Buffer A(20mM Tris,300mM NaCl,10%Glycerol,pH8.0)中,再向透析产物中加入适量的SUMO蛋白酶(SUMO Protease),混匀后,4℃反应24h。
8.2将反应物缓慢加入Ni-NTA亲和层析柱,收集流出液。
8.3利用Buffer A清洗层析柱,收集清洗液。
8.4利用Buffer D洗脱,收集洗脱液。
8.5 SDS-PAGE分析。
8.6 SDS-PAGE电泳,如图7所示,其中
M:蛋白质分子量标记(Protein Marker)
1:酶切反应前样品
2:酶切反应后样品
3:酶切后过柱流出样(肝素酶I)
4:酶切后过柱清洗样
5:酶切后过柱洗脱样(SUMO蛋白标签)。
综上,将正确的质粒转化至BL21(DE3)大肠杆菌感受态细胞中,挑取单克隆,经SDS-PAGE验证,融合蛋白表达正常。各优化条件下,融合蛋白均表达明显,且融合蛋白在15℃诱导温度下可溶性更好,选择15℃下0.2mM IPTG诱导,Ni-NTA纯化后去除标签得到无融合标签的目的蛋白肝素酶I。
当然,本发明还可有其他实施例,在不背离本发明精神及其实质的情况下,所属技术领域的技术人员当可根据本发明作出各种相应的改变和变形,但这些相应的改变和变形都应属于本发明的权利要求的保护范围。
SEQ ID No.1:
肝素酶I(Heparinase I)的氨基酸序列:
MKKQILYLIVLQQLFLCSAYAQQKKSGNIPYRVNVQADSAKQKAIIDNKWVAVGINKPYALQYDDKLRFNGKPSYRFELKAEDNSLEGYAAGETKGRTELSYSYATTNDFKKFPPSVYQNAQKLKTVYHYGKGICEQGSSRSYTFSVYIPSSFPDNATTIFAQWHGAPSRTLVATPEGEIKTLSIEEFLALYDRMIFKKNIAHDKVEKKDKDGKITYVAGKPNGWKVEQGGYPTLAFGFSKGYFYIKANSDRQWLTDKADRNNANPENSEVMKPYSSEYKTSTIAYKMPFAQFPKDCWITFDVAIDWTKYGKEANTILKPGKLDVMMTYTKNKKPQKAHIVNQQEILIGRNDDDGYYFKFGIYRVGNSTVPVTYNLSGYSETAR
SEQ ID No.2:
肝素酶I(Heparinase I)DNA:
CAACAAAAAAAAAGCGGAAACATACCATACAGAGTAAACGTACAAGCAGACAGCGCAAAACAAAAAGCAATAATAGACAACAAATGGGTAGCAGTAGGAATAAACAAACCATACGCACTACAATACGACGACAAACTAAGATTCAACGGAAAACCAAGCTACAGATTCGAACTAAAAGCAGAAGACAACAGCCTAGAAGGATACGCAGCAGGAGAAACAAAAGGAAGAACAGAACTAAGCTACAGCTACGCAACAACAAACGACTTCAAAAAATTCCCACCAAGCGTATACCAAAACGCACAAAAACTAAAAACAGTATACCACTACGGAAAAGGAATATGCGAACAAGGAAGCAGCAGAAGCTACACATTCAGCGTATACATACCAAGCAGCTTCCCAGACAACGCAACAACAATATTCGCACAATGGCACGGAGCACCAAGCAGAACACTAGTAGCAACACCAGAAGGAGAAATAAAAACACTAAGCATAGAAGAATTCCTAGCACTATACGACAGAATGATATTCAAAAAAAACATAGCACACGACAAAGTAGAAAAAAAAGACAAAGACGGAAAAATAACATACGTAGCAGGAAAACCAAACGGATGGAAAGTAGAACAAGGAGGATACCCAACACTAGCATTCGGATTCAGCAAAGGATACTTCTACATAAAAGCAAACAGCGACAGACAATGGCTAACAGACAAAGCAGACAGAAACAACGCAAACCCAGAAAACAGCGAAGTAATGAAACCATACAGCAGCGAATACAAAACAAGCACAATAGCATACAAAATGCCATTCGCACAATTCCCAAAAGACTGCTGGATAACATTCGACGTAGCAATAGACTGGACAAAATACGGAAAAGAAGCAAACACAATACTAAAACCAGGAAAACTAGACGTAATGATGACATACACAAAAAACAAAAAACCACAAAAAGCACACATAGTAAACCAACAAGAAATACTAATAGGAAGAAACGACGACGACGGATACTACTTCAAATTCGGAATATACAGAGTAGGAAACAGCACAGTACCAGTAACATACAACCTAAGCGGATACAGCGAAACAGCAAGATAG
SEQ ID No.3:
SUMO-肝素酶I融合蛋白的氨基酸序列(SUMO-Heparinase I):
MGHHHHHHMSDSEVNQEAKPEVKPEVKPETHINLKVSDGSSEIFFKIKKTTPLRRLMEAFAKRQGKEMDSLRFLYDGIRIQADQTPEDLDMEDNDIIEAHREQIGGQGSQSSSITRKDFDHINLEYSGLEKVNKAVAAGNYDDAAKALLAYYREKSKAREPDFSNAEKPADIRQPIDKVTREMADKALVHQFQPHKGYGYFDYGKDINWQMWPVKDNEVRWQLHRVKWWQAMALVYHATGDEKYAREWVYQYSDWARKNPLGLSQDNDKFVWRPLEVSDRVQSLPPTFSLFVNSPAFTPAFLMEFLNSYHQQADYLSTHYAEQGNHRLFEAQRNLFAGVSFPEFKDSPRWRQTGISVLNTEIKKQVYADGMQFELSPIYHVAAIDIFLKAYGSAKRVNLEKEFPQSYVQTVENMIMALISISLPDYNTPMFGDSWITDKNFRMAQFASWARVFPANQAIKYFATDGKQGKAPNFLSKALSNAGFYTFRSGWDKNATVMVLKASPPGEFHAQPDNGTFELFIKGRNFTPDAGVFVYSGDEAIMKLRNWYRQTRIHSTLTLDNQNMVITKARQNKWETGNNLDVLTYTNPSYPNLDHQRSVLFINKKYFLVIDRAIGEATGNLGVHWQLKEDSNPVFDKTKNRVYTTYRDGNNLMIQSLNADRTSLNEEEGKVSYVYNKELKRPAFVFEKPKKNAGTQNFVSIVYPYDGQKAPEISIRENKGNDFEKGKLNLTLTINGKQQLVLVP
序列表
<110> 上海宝维医药技术有限公司
<120> 一种利用SUMO融合表达系统制备重组肝素酶I的方法及其所制备的SUMO_肝素酶I融合蛋白
<130> 2020
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
<211> 384
<212> PRT
<213> 人工序列()
<400> 1
Met Lys Lys Gln Ile Leu Tyr Leu Ile Val Leu Gln Gln Leu Phe Leu
1 5 10 15
Cys Ser Ala Tyr Ala Gln Gln Lys Lys Ser Gly Asn Ile Pro Tyr Arg
20 25 30
Val Asn Val Gln Ala Asp Ser Ala Lys Gln Lys Ala Ile Ile Asp Asn
35 40 45
Lys Trp Val Ala Val Gly Ile Asn Lys Pro Tyr Ala Leu Gln Tyr Asp
50 55 60
Asp Lys Leu Arg Phe Asn Gly Lys Pro Ser Tyr Arg Phe Glu Leu Lys
65 70 75 80
Ala Glu Asp Asn Ser Leu Glu Gly Tyr Ala Ala Gly Glu Thr Lys Gly
85 90 95
Arg Thr Glu Leu Ser Tyr Ser Tyr Ala Thr Thr Asn Asp Phe Lys Lys
100 105 110
Phe Pro Pro Ser Val Tyr Gln Asn Ala Gln Lys Leu Lys Thr Val Tyr
115 120 125
His Tyr Gly Lys Gly Ile Cys Glu Gln Gly Ser Ser Arg Ser Tyr Thr
130 135 140
Phe Ser Val Tyr Ile Pro Ser Ser Phe Pro Asp Asn Ala Thr Thr Ile
145 150 155 160
Phe Ala Gln Trp His Gly Ala Pro Ser Arg Thr Leu Val Ala Thr Pro
165 170 175
Glu Gly Glu Ile Lys Thr Leu Ser Ile Glu Glu Phe Leu Ala Leu Tyr
180 185 190
Asp Arg Met Ile Phe Lys Lys Asn Ile Ala His Asp Lys Val Glu Lys
195 200 205
Lys Asp Lys Asp Gly Lys Ile Thr Tyr Val Ala Gly Lys Pro Asn Gly
210 215 220
Trp Lys Val Glu Gln Gly Gly Tyr Pro Thr Leu Ala Phe Gly Phe Ser
225 230 235 240
Lys Gly Tyr Phe Tyr Ile Lys Ala Asn Ser Asp Arg Gln Trp Leu Thr
245 250 255
Asp Lys Ala Asp Arg Asn Asn Ala Asn Pro Glu Asn Ser Glu Val Met
260 265 270
Lys Pro Tyr Ser Ser Glu Tyr Lys Thr Ser Thr Ile Ala Tyr Lys Met
275 280 285
Pro Phe Ala Gln Phe Pro Lys Asp Cys Trp Ile Thr Phe Asp Val Ala
290 295 300
Ile Asp Trp Thr Lys Tyr Gly Lys Glu Ala Asn Thr Ile Leu Lys Pro
305 310 315 320
Gly Lys Leu Asp Val Met Met Thr Tyr Thr Lys Asn Lys Lys Pro Gln
325 330 335
Lys Ala His Ile Val Asn Gln Gln Glu Ile Leu Ile Gly Arg Asn Asp
340 345 350
Asp Asp Gly Tyr Tyr Phe Lys Phe Gly Ile Tyr Arg Val Gly Asn Ser
355 360 365
Thr Val Pro Val Thr Tyr Asn Leu Ser Gly Tyr Ser Glu Thr Ala Arg
370 375 380
<210> 2
<211> 1092
<212> DNA
<213> 人工序列()
<400> 2
caacaaaaaa aaagcggaaa cataccatac agagtaaacg tacaagcaga cagcgcaaaa 60
caaaaagcaa taatagacaa caaatgggta gcagtaggaa taaacaaacc atacgcacta 120
caatacgacg acaaactaag attcaacgga aaaccaagct acagattcga actaaaagca 180
gaagacaaca gcctagaagg atacgcagca ggagaaacaa aaggaagaac agaactaagc 240
tacagctacg caacaacaaa cgacttcaaa aaattcccac caagcgtata ccaaaacgca 300
caaaaactaa aaacagtata ccactacgga aaaggaatat gcgaacaagg aagcagcaga 360
agctacacat tcagcgtata cataccaagc agcttcccag acaacgcaac aacaatattc 420
gcacaatggc acggagcacc aagcagaaca ctagtagcaa caccagaagg agaaataaaa 480
acactaagca tagaagaatt cctagcacta tacgacagaa tgatattcaa aaaaaacata 540
gcacacgaca aagtagaaaa aaaagacaaa gacggaaaaa taacatacgt agcaggaaaa 600
ccaaacggat ggaaagtaga acaaggagga tacccaacac tagcattcgg attcagcaaa 660
ggatacttct acataaaagc aaacagcgac agacaatggc taacagacaa agcagacaga 720
aacaacgcaa acccagaaaa cagcgaagta atgaaaccat acagcagcga atacaaaaca 780
agcacaatag catacaaaat gccattcgca caattcccaa aagactgctg gataacattc 840
gacgtagcaa tagactggac aaaatacgga aaagaagcaa acacaatact aaaaccagga 900
aaactagacg taatgatgac atacacaaaa aacaaaaaac cacaaaaagc acacatagta 960
aaccaacaag aaatactaat aggaagaaac gacgacgacg gatactactt caaattcgga 1020
atatacagag taggaaacag cacagtacca gtaacataca acctaagcgg atacagcgaa 1080
acagcaagat ag 1092
<210> 3
<211> 744
<212> PRT
<213> 人工序列()
<400> 3
Met Gly His His His His His His Met Ser Asp Ser Glu Val Asn Gln
1 5 10 15
Glu Ala Lys Pro Glu Val Lys Pro Glu Val Lys Pro Glu Thr His Ile
20 25 30
Asn Leu Lys Val Ser Asp Gly Ser Ser Glu Ile Phe Phe Lys Ile Lys
35 40 45
Lys Thr Thr Pro Leu Arg Arg Leu Met Glu Ala Phe Ala Lys Arg Gln
50 55 60
Gly Lys Glu Met Asp Ser Leu Arg Phe Leu Tyr Asp Gly Ile Arg Ile
65 70 75 80
Gln Ala Asp Gln Thr Pro Glu Asp Leu Asp Met Glu Asp Asn Asp Ile
85 90 95
Ile Glu Ala His Arg Glu Gln Ile Gly Gly Gln Gly Ser Gln Ser Ser
100 105 110
Ser Ile Thr Arg Lys Asp Phe Asp His Ile Asn Leu Glu Tyr Ser Gly
115 120 125
Leu Glu Lys Val Asn Lys Ala Val Ala Ala Gly Asn Tyr Asp Asp Ala
130 135 140
Ala Lys Ala Leu Leu Ala Tyr Tyr Arg Glu Lys Ser Lys Ala Arg Glu
145 150 155 160
Pro Asp Phe Ser Asn Ala Glu Lys Pro Ala Asp Ile Arg Gln Pro Ile
165 170 175
Asp Lys Val Thr Arg Glu Met Ala Asp Lys Ala Leu Val His Gln Phe
180 185 190
Gln Pro His Lys Gly Tyr Gly Tyr Phe Asp Tyr Gly Lys Asp Ile Asn
195 200 205
Trp Gln Met Trp Pro Val Lys Asp Asn Glu Val Arg Trp Gln Leu His
210 215 220
Arg Val Lys Trp Trp Gln Ala Met Ala Leu Val Tyr His Ala Thr Gly
225 230 235 240
Asp Glu Lys Tyr Ala Arg Glu Trp Val Tyr Gln Tyr Ser Asp Trp Ala
245 250 255
Arg Lys Asn Pro Leu Gly Leu Ser Gln Asp Asn Asp Lys Phe Val Trp
260 265 270
Arg Pro Leu Glu Val Ser Asp Arg Val Gln Ser Leu Pro Pro Thr Phe
275 280 285
Ser Leu Phe Val Asn Ser Pro Ala Phe Thr Pro Ala Phe Leu Met Glu
290 295 300
Phe Leu Asn Ser Tyr His Gln Gln Ala Asp Tyr Leu Ser Thr His Tyr
305 310 315 320
Ala Glu Gln Gly Asn His Arg Leu Phe Glu Ala Gln Arg Asn Leu Phe
325 330 335
Ala Gly Val Ser Phe Pro Glu Phe Lys Asp Ser Pro Arg Trp Arg Gln
340 345 350
Thr Gly Ile Ser Val Leu Asn Thr Glu Ile Lys Lys Gln Val Tyr Ala
355 360 365
Asp Gly Met Gln Phe Glu Leu Ser Pro Ile Tyr His Val Ala Ala Ile
370 375 380
Asp Ile Phe Leu Lys Ala Tyr Gly Ser Ala Lys Arg Val Asn Leu Glu
385 390 395 400
Lys Glu Phe Pro Gln Ser Tyr Val Gln Thr Val Glu Asn Met Ile Met
405 410 415
Ala Leu Ile Ser Ile Ser Leu Pro Asp Tyr Asn Thr Pro Met Phe Gly
420 425 430
Asp Ser Trp Ile Thr Asp Lys Asn Phe Arg Met Ala Gln Phe Ala Ser
435 440 445
Trp Ala Arg Val Phe Pro Ala Asn Gln Ala Ile Lys Tyr Phe Ala Thr
450 455 460
Asp Gly Lys Gln Gly Lys Ala Pro Asn Phe Leu Ser Lys Ala Leu Ser
465 470 475 480
Asn Ala Gly Phe Tyr Thr Phe Arg Ser Gly Trp Asp Lys Asn Ala Thr
485 490 495
Val Met Val Leu Lys Ala Ser Pro Pro Gly Glu Phe His Ala Gln Pro
500 505 510
Asp Asn Gly Thr Phe Glu Leu Phe Ile Lys Gly Arg Asn Phe Thr Pro
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Asp Ala Gly Val Phe Val Tyr Ser Gly Asp Glu Ala Ile Met Lys Leu
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Arg Asn Trp Tyr Arg Gln Thr Arg Ile His Ser Thr Leu Thr Leu Asp
545 550 555 560
Asn Gln Asn Met Val Ile Thr Lys Ala Arg Gln Asn Lys Trp Glu Thr
565 570 575
Gly Asn Asn Leu Asp Val Leu Thr Tyr Thr Asn Pro Ser Tyr Pro Asn
580 585 590
Leu Asp His Gln Arg Ser Val Leu Phe Ile Asn Lys Lys Tyr Phe Leu
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Val Ile Asp Arg Ala Ile Gly Glu Ala Thr Gly Asn Leu Gly Val His
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Trp Gln Leu Lys Glu Asp Ser Asn Pro Val Phe Asp Lys Thr Lys Asn
625 630 635 640
Arg Val Tyr Thr Thr Tyr Arg Asp Gly Asn Asn Leu Met Ile Gln Ser
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Leu Asn Ala Asp Arg Thr Ser Leu Asn Glu Glu Glu Gly Lys Val Ser
660 665 670
Tyr Val Tyr Asn Lys Glu Leu Lys Arg Pro Ala Phe Val Phe Glu Lys
675 680 685
Pro Lys Lys Asn Ala Gly Thr Gln Asn Phe Val Ser Ile Val Tyr Pro
690 695 700
Tyr Asp Gly Gln Lys Ala Pro Glu Ile Ser Ile Arg Glu Asn Lys Gly
705 710 715 720
Asn Asp Phe Glu Lys Gly Lys Leu Asn Leu Thr Leu Thr Ile Asn Gly
725 730 735
Lys Gln Gln Leu Val Leu Val Pro
740
Claims (8)
1.一种利用SUMO融合表达系统制备重组肝素酶I的方法,其特征在于,包括下列步骤:
S01:选择来自肝素黄杆菌(Pedobacter heparinus)的肝素酶I序列,其氨基酸序列如SEQIDNo.1所示,共384aa;
S02:去除信号肽序列,获得肝素酶I的DNA序列,如SEQIDNo.2;
S03:将所述肝素酶I的DNA序列插入带有N端SUMO蛋白标签的pSMART载体质粒;
S04:将正确的质粒转化至BL21(DE3)大肠杆菌感受态细胞中,挑取单克隆,经发酵和纯化获得SUMO_肝素酶I融合蛋白;
S05:用SUMO蛋白酶将SUMO标签蛋白从步骤S04所述的SUMO_肝素酶I融合蛋白上切割下来,即获得肝素酶I。
2.根据权利要求1所述的方法,其特征在于,还包括融合蛋白表达条件的优化步骤。
3.根据权利要求2所述的方法,其特征在于,所述融合蛋白的优化条件是融合蛋白在15℃以0.2mmol/l异丙基硫代半乳糖苷(IPTG)诱导表达。
4.根据权利要求1-3所述的方法,其特征在于,还包括融合蛋白的纯化步骤。
5.根据权利要求4所述的方法,其特征在于,所述融合蛋白的纯化步骤采用Ni柱亲和层析方法进行分离纯化。
6.根据权利要求1所述的方法,其特征在于,所述的SUMO标签蛋白从步骤S04所述的SUMO_肝素酶I融合蛋白上切割下来是包括下列步骤:将所述融合蛋白透析更换缓冲液,加入适量的SUMO蛋白酶,混匀后置于4℃反应过夜,水解后的融合蛋白样本用Ni柱亲和层析方法将带有6个组氨酸片段的SUMO蛋白标签(能结合到Ni柱上)与肝素酶I(不能结合到Ni柱上)分离。
7.权利要求1-5任一项所述的方法制备的SUMO_肝素酶I融合蛋白,其特征在于,所述融合蛋白的氨基酸序列如SEQIDNo.3。
8.权利要求1-5任一项所述的方法制备的肝素酶I。
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102234640A (zh) * | 2010-04-22 | 2011-11-09 | 哈尔滨市哈科隆生物制药研究所 | 重组小分子泛素样修饰物蛋白酶及其制备方法和应用 |
CN102634555A (zh) * | 2005-11-03 | 2012-08-15 | 莫曼塔医药品有限公司 | 硫酸乙酰肝素粘多糖裂解酶及其用途 |
CN103160487A (zh) * | 2011-12-15 | 2013-06-19 | 曹林 | 肝素酶i融合蛋白 |
CN103992995A (zh) * | 2014-06-05 | 2014-08-20 | 山东大学 | 一种高表达水溶性肝素酶i融合蛋白及其编码基因 |
CN106497897A (zh) * | 2016-10-26 | 2017-03-15 | 天津科技大学 | 一种提高肝素酶i活性的工程菌株构建方法 |
CN109321549A (zh) * | 2018-09-18 | 2019-02-12 | 天津科技大学 | 一种比酶活提高的肝素酶i的定向改造酶及分子改造方法和表达工程菌 |
CN109385412A (zh) * | 2018-09-18 | 2019-02-26 | 天津科技大学 | 一种高表达高活性多形拟杆菌肝素酶i融合蛋白及其编码基因和应用 |
CN109706137A (zh) * | 2019-01-21 | 2019-05-03 | 天津科技大学 | 一种通过增加二硫键提高肝素酶i热稳定性的突变体及制备方法 |
CN111705032A (zh) * | 2020-07-09 | 2020-09-25 | 科赫生物科技(北京)有限公司 | 一种原核表达细胞及其制备方法和应用 |
-
2021
- 2021-01-25 CN CN202110097126.5A patent/CN112980820A/zh active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102634555A (zh) * | 2005-11-03 | 2012-08-15 | 莫曼塔医药品有限公司 | 硫酸乙酰肝素粘多糖裂解酶及其用途 |
CN102234640A (zh) * | 2010-04-22 | 2011-11-09 | 哈尔滨市哈科隆生物制药研究所 | 重组小分子泛素样修饰物蛋白酶及其制备方法和应用 |
CN103160487A (zh) * | 2011-12-15 | 2013-06-19 | 曹林 | 肝素酶i融合蛋白 |
CN103992995A (zh) * | 2014-06-05 | 2014-08-20 | 山东大学 | 一种高表达水溶性肝素酶i融合蛋白及其编码基因 |
CN106497897A (zh) * | 2016-10-26 | 2017-03-15 | 天津科技大学 | 一种提高肝素酶i活性的工程菌株构建方法 |
CN109321549A (zh) * | 2018-09-18 | 2019-02-12 | 天津科技大学 | 一种比酶活提高的肝素酶i的定向改造酶及分子改造方法和表达工程菌 |
CN109385412A (zh) * | 2018-09-18 | 2019-02-26 | 天津科技大学 | 一种高表达高活性多形拟杆菌肝素酶i融合蛋白及其编码基因和应用 |
CN109706137A (zh) * | 2019-01-21 | 2019-05-03 | 天津科技大学 | 一种通过增加二硫键提高肝素酶i热稳定性的突变体及制备方法 |
CN111705032A (zh) * | 2020-07-09 | 2020-09-25 | 科赫生物科技(北京)有限公司 | 一种原核表达细胞及其制备方法和应用 |
Non-Patent Citations (1)
Title |
---|
赵善成;王振;程咏梅;陈敬华;: "一种SUMO-Heparinase Ⅰ融合酶的可溶性表达与纯化", 食品与生物技术学报, no. 03 * |
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