CN1151762A - 非毒性、非产毒性、非致病性镰孢属表达系统及所用启动子和终止子 - Google Patents

非毒性、非产毒性、非致病性镰孢属表达系统及所用启动子和终止子 Download PDF

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CN1151762A
CN1151762A CN95193875A CN95193875A CN1151762A CN 1151762 A CN1151762 A CN 1151762A CN 95193875 A CN95193875 A CN 95193875A CN 95193875 A CN95193875 A CN 95193875A CN 1151762 A CN1151762 A CN 1151762A
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J·C·洛耶
D·L·墨耶
W·约德
J·R·舒斯特
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Abstract

本发明涉及一种非毒性、非产毒性、非致病性重组镰孢(Fusarium)，如禾本科镰孢(Fusarium)如禾本科镰孢(Fusarium graminearum)宿主细胞，它包括一个与一个启动子可操纵连接的编码一种异源蛋白质的核酸序列。本发明还涉及一种利用这种镰孢宿主细胞生产重组蛋白的方法，本发明还涉及可用于这种细胞的一个启动子和终止子序列。

Description

非毒性、非产毒性、非致病性镰孢属表达 系统及所用启动子和终止子
本发明涉及用于重组蛋白生产的宿主细胞.具体地讲，本发明涉及非毒性、非产毒性、非致病性镰孢属(Fusarium)真菌宿主细胞，可将其用于重组蛋白，尤其是酶的高水平表达。本发明还涉及可用于该系统的启动子序列和终止子序列。
近年来，由于将重组宿主细胞用于表达异源蛋白，已极大地简化了大量有商业价值的蛋白质的生产，这种蛋白质原来只能从其天然来源中纯化.目前，已有多种可选择的表达系统，可从中选择生产任何特定蛋白质所需的表达系统，包括原核宿主和真核宿主。适当表达系统的选择通常不仅取决于宿主细胞产生适量产率所述蛋白质的能力，而且在很大程度上取决于预想的该蛋白质的最终用途。
尽管哺乳动物细胞和酵母细胞一直是最常用的真核宿主，但现在已开始认识到丝状真菌是可用于重组蛋白质生产的很有用的宿主细胞.现在被利用或被推荐用于上述方法的丝状真菌的例子有：粗糙脉孢霉(Neurospora crassa)、Acremonium chrysogenum、Tolypocladium geodes、卷枝毛霉(Mucor circinelloides)和Trichoderma reesei，构巢曲霉(Aspergillus nidulans)、黑曲霉(A.niger)和米曲霉(A.oryzae)。
镰孢属的某些种已被用作植物致病性研究和基因调控研究的模式系统，如尖镰孢(Fusarium oxysporum)(Dioletz等，1993，Gene131：61-67；Langin等，1990，Curr Genet.17：313-319；Malardier等，1989，Gene 78：147-156和Kistler及Benny，1988，Curr，Genet.13：145-149)、腐皮镰孢(F.solani)(Crowhurst等，1992，Curr，Gene.21：463-469)和大刀镰孢(Fusarium culmorum)(Curragh等，1992，Mycol.Res.97：313-317)。这些镰孢菌不适用于异源蛋白的商品化生产，因为它们具有一些不理想的特征，例如，是植物病原体，或是会产生超过安全水平的真菌毒素。Dickman和Leslie(1992，Mol.Gen.Genet.235：458-462)披露了用一种带有粗糙脉孢霉的nit-2的质粒转化玉蜀黍赤霉(Gibberella.zeae)的方法。由Dickman和Leslie披露的玉蜀黍赤霉菌株是一种植物病原体，并能产生玉米赤霉烯酮-一种雌激素类真菌毒素。Sanchez-Fernandez等(191，Mol.Gen.Genet.225：231-233)披露了用一种带有黑曲霉niaD基团的质粒转化具有niaD突变的藤仓赤霉(Gibberellafujikoroi)的方法。
理想的表达系统应当是这样的：它基本上不产生蛋白酶和真菌毒素，而且基本上没有大量其它内源产生的分泌性蛋白，它能以比现有宿主细胞更高的水平表达。本发明现在就提供满足上述要求的新型镰孢属表达系统。
本发明提供了一种重组的非毒性、非产毒性和非致病性镰孢属宿主细胞，它包括一个与一个启动子可操纵连接的编码一种异源蛋白的核酸序列.这里所说的“非毒性”是指该宿主细胞不是植物或动物的毒物。例如，如果以大约20ml(1∶1稀释)培养3天的镰孢属培养基/kg体重/小鼠的剂量给大约5只小鼠注射镰孢属培养基约14天之后，这些小鼠中无一只因镰孢处理而死亡的话，就认为这种镰孢宿主细胞是非毒性的。这里所说的“非产毒性”是指经标准分析方法，如HPLC分析测定基本没有真菌毒素的宿主细胞。例如，可用有机溶剂提取一定量的生长在盛有固体营养基的2×9cm培养皿上的镰孢菌，并将该提取物的0.5％加注到HPLC中进行分析。通过没有在真菌毒素标准的已知位置上出现可检测到的HPLC峰这一现象，可以推断没有已知的真菌毒素。这里所说的“非致病性”是指该宿主细胞不会导致健康植株或健康动物明显发病。例如，一种能使植物致病的镰孢菌，会出现对植物木质部组织的真菌性侵入，并导致以典型的枯萎症状为特征的病态。这里所说的“异源蛋白”是指一种对该宿主细胞来说不是天然的蛋白质，或是一种已通过修饰使其天然序列发生改变的天然蛋白质，或是一种对其表达做过定量改变的天然蛋白质，这种表达的定量改变可以是对表达该天然蛋白质所需的天然调节序列，如启动子、核糖体结合位点等进行操作的结果，或是用重组DNA技术对宿主细胞进行其它操作的结果。所述核酸序列可操纵连接在一个合适的启动子序列上，该启动子序列可指导所述核酸序列在所述选择的宿主细胞中转录。
本发明还涉及一种生产重组蛋白质的方法，该方法包括在有利于蛋白质表达的条件下培养上述菌种之一的宿主细胞，该宿主细胞带有一个编码一种异源蛋白质的核酸序列；以及从培养物中回收所述蛋白质。在一个优选实施方案中，所述蛋白质是一种真菌蛋白，最好是一种真菌酶。采用本发明的方法，至少能产生0.5g异源蛋白质/1宿主细胞。
出人意料的是，本发明的宿主细胞仅分泌少量蛋白酶，在下文的实施例1部分所公开的酪蛋白澄清试验证实了这一点；具体地讲，仅能检测到小的水解区或检测不到。本发明的宿主细胞和方法在某些真菌酶的生产方面出人意料地比其它已知真菌菌种，如黑曲霉、米曲霉或尖镰孢更为有效。
本发明还涉及一个由编码一种尖镰孢类胰蛋白酶蛋白酶的基因或其片断衍生的启动子序列，所述片断具有基本上与该序列相同的启动子活性。该启动子的序列如SEQ ID NO：5所示。
此外，本发明还涉及一个由编码一种尖镰孢类胰蛋白酶蛋白酶的基因或其片断衍生的终止子序列，所述片断具有基本上与该序列相同的终止子活性。该终止子的序列如SEQ ID NO：6所示。
图1表示由禾本科镰孢(Fusarium graminearum)(泳道1)、黑曲霉(泳道2)和米曲霉(泳道3)分泌的蛋白质的SDS凝胶电泳结果。泳道4表示分子量标记。
图2表示对下列样品进行的蛋白酶试验结果：米曲霉(孔1)；黑曲霉(孔2)；禾本科镰孢(孔3)；空白孔对照(孔4-6)。
图3表示质粒pJRoy6的构建。
图4表示对禾本科镰孢20334的转化体中所分泌的类胰蛋白酶蛋白酶进行SDS-PAGE分析的结果。泳道1：分子量标记：泳道2：空白；泳道3：纯化的类胰蛋白酶蛋白酶标准；泳道4：空白；泳道5：未转化的禾本科镰孢20334；泳道6：空白：泳道7：用质粒pJRoy6转化的禾本科镰孢菌株20334；泳道8：空白；泳道9：分子量标记。
图5表示pJRoy20的限制图。
图6表示pDM151的限制图。
图7表示pDM155的限制图。
图8A和8B表示当DSM151-4在禾本科镰孢中发酵20-160小时后Carezyme在禾本科镰孢中的表达水平。图8A表示Carezyme的分析结果。图8B表示对在所述禾本科镰孢中Carezyme产生的SDS-PAGE分析结果。泳道1：分子量标记；泳道2：20小时；泳道3：50小时；泳道4：70小时；泳道5：90小时；泳道6：120小时；泳道7：140小时；泳道8：160小时。
图9A和9B表示当DSM 155-10在禾本科镰孢中发酵20-160小时后Liploase的表达水平。图9A表示Lipolase分析结果。图9B表示对在所述禾本科镰孢中Liploase产生的SDS-PAGE分析结果。泳道1：分子量标记；泳道2：20小时；泳道3：50小时；泳道4：60小时；泳道5：90小时；泳道6：120小时；泳道7：140小时；泳道8：160小时。
图10表示pCaHj418的限制图。
图11表示pDM148的限制图。
图12表示pDM149的限制图。
图13表示pMHan37的限制图。
图14表示pDM154的限制图。
镰孢属的特征是：菌丝体伸展在培养中呈絮状，在固体培养基上的菌丝体常带有一些粉紫或黄色。分生孢子梗细长、长度不同而且是单的，或粗、短、不规则地分枝，或具有一个瓶梗螺环，单的或组合成分生孢子座。分生孢子主要有两类，通常藏在湿的小头中：几个细胞的大分生孢子，其尖尾略有卷曲或弯曲，一般为舟状；一个细胞的小分生孢子，卵圆形或长椭圆形，单生或呈链状。某些分生孢子为中等大小，2或3个细胞，长椭圆形或略有卷曲。
在一个具体实施方案中，本发明的宿主细胞是禾本科镰孢的种，它具有以下特征。分生孢子：无小分生孢子。大分生孢子明显有隔膜，厚壁，直至中等镰状，不均等弯曲，其腹面近于垂直而背面呈光滑的弧形。基细胞为特异足状。顶端细胞呈锥形或收缩成进口锥状。分生孢子梗：不分枝或分枝的单瓶梗。厚壁孢子：在培养物中通常极缓慢地生成：当确实发生时，它们最常见的是生成于大分生孢子上，但也可生成于菌丝体上。菌落形态学：在PDA培养基上生长迅速，具有稠密的气生菌丝体，这些菌丝体几乎充满试管，通常为黄色至黄褐色，其边缘呈白色至洋红色。假如有的话，红棕至橙色分生孢子座也是稀疏的，只有当培养物在30天以上龄时才会出现。其下表面通常为洋红色。这种真菌能产生任何类型褪色部分的直筒状(背面与腹面平行)的大分生孢子。
在一个最具体的实施方案中，所述禾本科镰孢是Fusariumgraminearum Schwabe IMI145425，由美国典型培养物保藏所保藏，编号为ATCC 20334(US专利号4,041,189)，以及它的衍生物和突变体，它们同样是非毒性、非产毒性和非致病性的，例如在U.S.专利号4,041,189中所披露的。
应当理解，在本说明书及权利要求中，所用的“禾本科镰孢(Fusarium graminearum)”不但指包括在该种内的有机体，而且包括那些原先是该种的有机体的种或目前在另一种分类体系中被称为其它的种，但是仍具有与上文中所述的形态特征和培养特征相同的特征的种，而且可能与禾本科镰孢同义。这些种包括(但不限于)Fusarium roseum，F.roseum var.graminearum，玉蜀黍赤霉或Gibberella roseum，Gibberella roseum f.sp.cerealis。
本领域技术人员还知道，对这里所述宿主菌种的成功转化并不局限于采用本文具体列举的载体、启动子和选择标记。一般而言，用于转化尖镰孢、腐皮镰孢和大刀镰孢的技术也可用于转化本发明的宿主细胞。例如，尽管amdS选择标记是优选的，其它可用的选择标记包括arg B(构巢曲霉或黑曲霉)、trp C(黑曲霉或构巢曲霉)、pyrG(黑曲霉、米曲霉或构巢曲霉)、niaD(构巢曲霉、黑曲霉或尖镰孢)、及hyg B(大肠杆菌)标记。所述启动子可以是在这些种中具有强转录活性的任何DNA序列，并可以由编码胞外和胞内蛋白质，如淀粉酶、葡糖淀粉酶、蛋白酶、脂肪酶、纤维素酶和糖酵解酶的基因衍生而来。所述启动子的例子包括(但不限于)构巢曲霉amdS启动子或来自用于糖酵解酶和基因的启动子，如TPI、ADH、GAPDH和PGK。所述启动子还可以是同源启动子，即某一基因的启动子是所用宿主菌株先天固有的。启动子序列还可以带有接头，以便引入特异限制性位点，有利于该启动子序列与所选择的基因连接，或与所选择的信号肽或前导区(preregion)连接。
所述启动子序列可以由一个编码尖镰孢类胰蛋白酶蛋白酶的基因或其片断衍生而来，该片断具有与该序列基本相同的启动子活性。所述启动子的序列如SEQ ID No：5所示。本发明还包括能在下列条件下与所述启动子序列杂交的核酸序列：在5×SSC中预浸泡，并在40℃下在由20％甲酰胺、5×Denhardt’s溶液、50mM磷酸钠、pH6.8和50μg变性的超声处理的小牛胸腺DNA组成的溶液中预杂交1小时，随后在大约40℃下在补充了100μM ATP的相同溶液中杂交18小时，接着在温度大约为45℃的0.4×SSC中洗涤；或者该核酸序列与SEQ ID No：5的同源性至少约为90％，最好约为95％，但它具有基本上与所述序列相同的启动子活性。在另一个实施方案中，所述启动子可以是包括大量AreA结合位点的一段序列，AreA是在氯限制期间表达的基因的正调节物；在粗糙脉孢霉中这些位点被称为nit-2(Fu和Marzlus，1990，Pro.Natl.Acad.Sci.U.S.A.87：5331-5335)。可通过增加或取代该AreA位点对上述启动子序列进行修饰。
终止子和聚腺苷酸化序列也可来自与所述启动子相同的序列。在一个特定实施方案中，终止子序列可以由一个编码尖镰孢类胰蛋白酶蛋白酶的基因或其片断衍生而来，所述片断具有基本上与该序列相同的终止子活性。该终止子的序列如SEQ ID No：6所示。本发明还包括能在下列条件下与所述终止子序列杂交的核酸序列：在5×SSC中预浸泡，并在大约40℃，在由20％甲酰胺、5×Denhandt’s溶液、50mM磷酸钠(pH6.8)和50μg变性的超声处理的小牛胸腺DNA组成的溶液中预杂交1小时，随后在40左右、在补充了100μM ATP的相同溶液中杂交18小时，接着在45℃左右的0.4×SSC中洗涤；或者该核酸序列与SEQ ID No：5的同源性至少约为90％，最好约为95％，但它具有基本上与所述序列相同的终止子活性。
还可以把增强子序列插入该构建体中。
为了避免破坏细胞以获取表达产物，并减少表达产物在细胞内可能发生的降解，该产物最好能被分泌到细胞外面。为此，在一个优选实施方案中，将目的基因同一个前导区，如信号肽或前导肽连接，该前导区可引导表达产物进入细胞的分泌途径。所述前导区可由任何生物的用于任何分泌性蛋白的基因衍生而来，或者是天然前导区。该前导区的可选来源有：曲霉菌的葡糖淀粉酶或淀粉酶基因、芽孢杆菌的淀粉酶基因、Rhizomucor miehei的脂肪酶或蛋白酶基因、来自酿酒酵母(Saccharomyces cerevisiae)的α-因子编码基因或小牛前凝乳酶(prochymosin)基因。所述前导区可来自用于米曲酶TAKA淀粉酶、黑曲霉中性α-淀粉酶、黑曲霉酸稳定性α-淀粉酶、地衣型芽孢杆菌(B.licheniformis)α-淀粉酶、来自芽孢杆菌NCIB11837的生麦淀粉酶、嗜热脂肪芽孢杆菌(B.stearothermophilus)α-淀粉酶或地衣型芽孢杆菌枯草蛋白酶的基因。有效的信号序列是米曲霉TAKA淀粉酶信号、Rhizomucor miehei天冬氨酸蛋白酶信号和Rhizomucor miehei脂肪酶信号。另外，还可以采用被表达基因的天然前导区，例如SEQID No：4中氨基酸-24至-5之间的片段。
同启动子和终止子序列功能性地连接着的用于目的产物的基因可以插入带有选择标记的一种载体中，或是携带在能够整合到宿主菌株的基因组里的一个单独的载体或质粒上。另外，所用的载体可以作为线状或环状染色体外因子在宿主细胞中复制。举例来说，这类载体包括质粒和微型染色体。所述载体系统可以是单个的载体或质粒，或者是共同携带有待整合到基因组中去的全部DNA的两个或两个以上的载体或质粒.载体或质粒可以是线状或闭环分子。
可采用本领域已知的方法，如转化法和电穿孔法(例如，参见Fincham，1989，Microbial Rev.53：148-170)，用编码所述异源蛋白的核酸转化宿主细胞。
可采用本领域已知的方法培养本发明的重组宿主细胞。简单地说，是在标准的生长培养基上培养宿主细胞，例如，那些含有无机盐、维生素、适当的有机碳源(如葡萄糖或淀粉)、各种复合营养源中的任一种(酵母提取物、水解酪蛋白、大豆粉等)的生长培养基。例子之一是FP-1培养基(5％大豆粉、5％葡萄糖、2％K2HPO4、0.2％CaCl2、0.2％MgSO4·7H2O和0.1％Pluronicacid(BASF))。在pH约为4.5-8.0和温度大约为20-37℃的条件下发酵大约2-7天。
本发明的宿主细胞可用于表达任何感兴趣的原核或真核异源蛋白，但最好用于表达真核蛋白质。这种宿主细胞的特别有用的用途是用于表达异源蛋白，特别是真菌酶。这种新型表达系统可用于表达各种酶，例如：过氧化氢酶、漆酶、酚氧化酶、氧化酶、氧化还原酶、纤维素酶、木聚糖酶、过氧化物酶、脂肪酶、水解酶、酯酶、角质酶、蛋白酶及其它蛋白酶、氨肽酶、羧肽酶、肌醇六磷酸酶、裂合酶、果胶酶及其它溶果胶酶、淀粉酶、葡糖淀粉酶、α-半乳糖苷酶、β-半乳糖苷酶、α-葡糖苷酶、β-葡糖苷酶、甘露糖苷酶、异构酶、转化酶、转移酶、核糖核酸酶、壳多糖酶、变位酶(mutanose)及脱氧核糖核酸酶。
在一个特定实施方案中，所述酶是一种碱性蛋白酶，例如尖镰孢前原胰蛋白酶(pre-pro-trypsin)基因。在一个最为具体的实施方案中，基因组序列如SEQ ID No：3所示，而蛋白质序列如SEQID No：4所示。
在另一个具体实施方案中，所述酶是一种碱性内切葡聚糖酶，它可与一种抗体发生免疫反应，这种抗体针对来自Humicolainsolens，DSM 1800的高度纯化的-43kD内切葡聚糖酶；或是具有纤维素酶活性的-43kD内切葡聚糖酶的衍生物(参见WO91/17243)。下文中称之为“Carezyme”的内切葡聚糖酶可以由SEQ ID NO：7所示的基因编码，并可以具有SEQ ID NO：8所示的蛋白质序列.这种酶还可以是Carezyme的变体。
在又一个具体实施方案中，所述酶是一种1，3-特异性脂肪酶，下文中称之为Lipolase的变体。这种酶可以由SEQ ID NO：9所述的DNA序列编码，并可以具有SEQ ID NO：10所示的氨基酸序列。这种酶还可以是Lipolase的变体，例如D96L，E210K、E210L(参见WO92/05249)。
本领域技术人员可以理解，“真菌酶”一词不仅包括天然真菌酶，而且还包括通过氨基酸取代、缺失、添加修饰过的真菌酶，或是对其进行其它修饰以增强其活性、热稳定性、pH耐受性等的真菌酶。本发明的宿主细胞还可用于表达有药用价值的异源蛋白，如激素、生长因子、受体等。
下面将通过非限定性实施例对本发明做进一步说明。
实施例
1.禾本科镰孢20334仅分泌少量的蛋白质
将禾本科镰孢菌株20334、米曲霉和黑曲霉的分生孢子悬浮液接种到盛在体积为125ml的摇瓶里的25ml YPD培养基(1％酵提取物(Difco)、2％细菌培养用胨(Difco)、2％葡萄糖)中，并在30℃、以300rpm的速度摇动的条件下培养5天。通过离心收集该培养物中的上清液。将每种样品共10μl与10μl 0.1M二硫苏糖醇(Sigma)和10μl加样缓冲液(40mM Tris碱、6％十二烷基硫酸钠、2.5mM EDTA、15％甘油、2mg/ml溴甲酚紫)混合。将上述样品煮沸5分钟，并在4-12％聚丙烯酰胺凝胶(Navex)上电泳5分钟。通过考马斯兰染色显现上述蛋白质。结果(图1)表明，禾本科镰孢菌株20334仅能产生极少的分泌性蛋白质。
2.禾本科镰孢20334仅分泌少量的蛋白酶
将来自禾本科镰孢菌株20334、米曲霉和黑曲霉的培养基(参见1.)共40μl各用移液管分别加注到在酪蛋白琼脂平皿(2％无脂奶粉(Lucerne)、50mM Tris-HCl pH＝7.5、1％惰性琼脂(Difco))上切出的孔中。将上述平皿在37℃培养5小时，并观察蛋白质水解范围。结果(图2)表明，禾本科菌株20334培养物只有极小的蛋白酶解活性。
3.尖镰孢基因组前原胰蛋白酶基因的克隆
由尖镰孢基因组DNA制备在λ噬菌体中的基因组文库，所采用的方法如Sambrook等在Molecular Cloning(A laboratoryManual，Cold Spring harber)N.Y.1989)一书中所述。将总计50μg基因组DNA放在含有10mM Tris(pH＝7.5)、50mM NaCl、7mMMgCl2、7mM2-巯基乙醇和4个单位的Sau3A限制酶的体积为200μl的溶液中，在37℃温度下消化1分钟。通过琼脂糖凝胶电泳分离分子大小为10-20kb的部分消化的DNA，接着电洗脱到透析膜上，并用一个Elutip-D柱(Schleicher和Schuell)进行浓缩。将1μg用限制酶BamHI切过、并用磷酸酶(Clonetech)处理过的EMBL4噬菌体的λ臂与300-400μg用Sau 3A切过的基因组DNA在25μl的体积中、在标准条件下连接(参见Sambrook等，1989，Molecular Cloning，A Laboratory Manual，cold Springharbor，NY)。采用一种商品化试剂盒(Gigapack Gold II，Stratagene)，按照生产商的说明由上述连接混合物制备λ噬菌体。
采用标准方法，铺平板培养大约15,000个重组λ噬菌体，并生产滤膜吸取物(吸至Hybond N+滤膜上，Amersham)(Sambrook，等，1989，Molecular Cloning，A LaboratoryManual，Cold Spring Harbar，NY)。按照标准方法(Sambrook等，1989，Molecular Cloning，A Laboratory Manual，ColdSpring Harbor，NY)处理该滤膜，与Genius试剂盒杂交，进行非放射性核酸检测.用作探针的DNA是用地高辛配基(DIG)标记的、存在于质粒pSX233上的尖镰孢类胰蛋白酶蛋白酶(以下称SP387)基因的完整编码区的0.75kb的PCR片段，该探针已由NRRL保藏，入藏号为NRRLB-21241。该PCR反应的引物是5′-tgcggatcc ATGGTCAAGTTCGCTTCCGTC(正向引物，SEQ ID NO：1)和5′-gacctcgag TTAAGCATAGGT GTCAATGAA(反向引物；SEQ ID NO：2)。在以上两个引物中，小写字母表示接头序列，而大写字母表示上述SP387基因的编码区。为了进行PCR，将25ng带有来自质粒pSx233的SP387基因的长度为907bp的BamH1/XbaI DNA片段，分别与68pmol的正向引物和反向引物混合。
将上述DNA片段与引物的混合物用1×Taq缓冲液/1×DIG标记Mix/5单位Taq(Boehringer Mannheim)调至80μl体积。反应条件为：95℃3分钟，然后进行这样的35个循环(95℃30秒，50℃1分钟，72℃1分钟)。通过PCR由尖镰孢类胰蛋白酶蛋白酶基因得到的DNA序列如SEQ ID NO：3所示。采用一种改进的(Engler和Blum，1993，Anal.Biochem.210：235-244)Genius试剂盒(Boehringer M-annheim)，用由DIG标记的探针筛选噬菌斑。分离阳性克隆并通过又一轮铺平皿培养和杂交进行纯化。制备带有尖镰孢类胰蛋白酶蛋白酶基因的重组λ噬菌体，并用Quiagenλmidi制备试剂盒(Quiagen)从该噬菌体中分离DNA。
4.表达质粒pJRoy6的构建
将限制作图、Southern印迹和杂交技术(Sambrook等，1989，Molecular Cloning，A Laboratory Manual，Cold SpringHarbor，NY)用于鉴定来自所述重组噬菌体之一的一个5.5kb的Pst1限制酶片段，它带有尖镰孢类胰蛋白酶蛋白酶编码基因及侧翼DNA序列。将这个5.5kb的Pst1片段亚克隆到Pst1消化的pUC118上，并将质粒命名为pJRoy4(见图3)。用限制酶EcoR1消化质粒pJRoy4，分离带有SP387基因和pUC118多接头的43bpEcoR1/Pst1区的3.5kb的EcoRI片段，并将其亚克隆到载体pToC90上，制成质粒pJRoy6(图3)。
5. SP387表达盒的构建
构建一种带有SP387启动子和终止子的表达盒(pJRoy20)，该表达盒是通过把所述启动子和终止子连接在pUC118上的BamH1位点而构成的。已将带有pJRoy20的大肠杆菌菌株保藏在NRRL。上述启动子片段是通过用EcoR1(切点为-1200)和Nco1(切点为翻译起始位点，见图5)消化SP387载体pJRoy6而产生的。上述终止子序列(图5中的碱基从2056-3107)是通过PCR扩增而产生的，扩增反应使用以下寡核苷酸：
正向
5′  gcacaccatggtcgctggatccATACCTTGTTGGAAGCGTCG3′(SEQ ID N：11)
反向
5′  atcggagcatgcggtaccgtttaaacgaatta AGGTAAACAAGATATAATTTTCTG3′(SEQ ID NO：12)
大写字母与SP387终止子DNA互补，而小写字母是带有工程限制位点的尾部。
在用Nco1和Sph1消化之后，分离所产生的带有终止子的扩增产物，在该终止子靠近5′末端的一侧有Nc01和BamH1位点，而在靠近其3′末端的一侧有EcoR1、Pme1、Kpn 1和Sph1位点。连接上述启动子片段、终止子片段和用Kpn1/Sph1切过的pUC118三者，以制成pJRoy20(见图5)。
6. Carezyme构建体
将位于SP387启动子的-15位置上的EcoRV位点和位于Carezyme编码区的+243位置上的Nco1位点用于在SP387启动子与Carezyme基因之间产生正确融合。采用以下引物由Carezyme载体pCaHj418(见图10)产生PCR片段，该片段带有SP387上-18至-1的片段，紧接着是Carezyme基因上-1至+294的片段。
正向
EcoRV
5′  ctcttggatatctatctcttcaccATGCGTTCCTCCCCCCTCCT3′  (SEQ ID NO：13)
反向
5′  CAATAGAGGTGGCAGCAAAA3′  (SEQ ID NO：14)
正向引物里的小写字母是SP387启动子上从-24至-1处的bp，而大写字母是Carezyme上从1至20处的bp。
所采用的PCR条件为：95℃5分钟，接着进行30个循环(95℃30秒，50℃1分钟，72℃1分钟).用Invitrogen’s TA克隆试剂盒把所得到的0.32kb片段克隆到载体pCRII上，制成pDM148(见图11)。从pDM148中分离0.26kb的EcoRV/Nco1片段，并用来自pCaHj418的0.69kb Ncol/Bg III片段连接，再将其克隆到用EcoRV/BamH1消化过的pJRoy20上，制成pDM149(见图12)。将3.2kb EcoR1 Carezyme表达盒(SP387启动子/Carezyme/SP387终止子)从pDM149上分离下来，并将其克隆到pToC90的EcoR1位点上，以制成pDM151(见图6)。表达构建体pDM151带有上述表达盒和amd S选择标记。已把带有pDM151的大肠杆菌菌株保藏在NRRL。
7. Lipolase构建体
将位于SP387启动子的-15位置上的Ec0RV位点和位于Lipolase编码区的+6位置上的Sacl位点用于在SP387启动子和Lipolase基因之间产生正确融合。构建一个带有SP387启动子的最后15个bp、后接Lipolase编码区的前6个bp的衔接头，该接头如下所示。
EcoRV            SacI
atctatctcttcaccATGAGGAGCT       (SEQ ID NO：15)
tagatagagaagtggTACTCC           (SEQ ID NO：16)
LipolasecDNA基因的一个0.9kb SacI/BamHI片段是从米曲霉表达构建体pMHan37(见图13)上分离的。连接所述EcoRV/SacI衔接头和SacI/BamHI Lipolase片段，并将其克隆到用EcoRV/BamHI消化的pJRoy20上，制成质粒pDM154(见图14)。从pDM154上分离3.2kb的KpnI Lipolase表达盒(SP387启动子/Lipolase/SP387终止子)，并将其克隆到pToC90的KpnI位点上，制成质粒pDM155(见图7)。表达构建体pDM155带有Lipolase表达盒和amdS选择标记。已将携带pDM151的大肠杆菌菌株保藏在NRRL。
8.禾本科镰孢的转化
在25℃下，将禾本科镰孢菌株ATCC20334培养物在加有1.5％葡萄糖和1.5％琼脂的Vogels培养基(Vogel，1964，Am.Nature98：435-446)的培养皿(100×15mm)上生长3周。用移菌环把分生孢子(每皿约108个)移至10ml无菌水中，并通过4层干酪包布、最后通过一层米拉布(miracloth)过滤而进行纯化。离心浓缩分生孢子。用108个分生孢子接种50mlYPG(1％酵母提取物(Difco)、2％细胞培养用胨(Difco)、2％葡萄糖)，并在20℃和150rpm的条件下培养14小时。把所得菌丝截留在无菌的0.4m滤膜上，并用消毒蒸馏水和1.0M MgSO4连续洗涤。将上述菌丝重新悬浮在10ml Novozym234(Novo Nordisk)溶液(2-10mg/ml，溶于1.0MMgSO4中)里，并在34℃下以80rpm速度振荡的条件下消化15-30分钟。通过用4层干酪包布和米拉布进行连续过滤，将未消化的菌丝材料从所得原生质体中除去。让20ml1M山梨醇通过上述干酪包布和米拉布，并与原生质体溶液合并。混合以后，通过离心使原生质体(约5×108个)沉淀，并通过在20ml 1M山梨醇中和在20ml STC(0.8m山梨醇，50mM Tris-HClpH-8.0，50mM CaCl2)中进行再悬浮和离心连续洗涤原生质体。将洗涤过的原生质体再悬浮于4份STC和1份SPTC(0.8M山梨醇，4％聚乙二醇4000(BDH)，50mM Tris-HCl pH＝8.0，50mMCaCl2)中，浓度为1-2×108/ml。将100μl原生质体悬浮液加进盛于聚丙烯试管(17×100mm)中的5μg pJRoy6和5μl肝素(以5mg/ml的浓度溶于STC中)里，并在冰上培养30分钟。将1ml SPTC轻轻混入上述原生质体悬浮液中，并在室温下继续培养20分钟。将原生质体铺在一种选择培养基上，该培养基由加有10mM乙酰胺的Cove盐(Cove，D.J.1966，Biochem.Biophys.Acta113：51-56)、15mMCsCl2/2.5％惰性琼脂(Difco)和1.0M蔗糖组成，并在该培养基上叠放一层含有0.6M蔗糖和1.0％低熔点琼脂糖(Sigma)的相同培养基。将培养皿在25℃温度下培养，转化子在第6-21天出现。
9.类胰蛋白酶蛋白酶在禾本科镰孢中的表达
将转化体转移到COVE2培养基(与上述COVE培养基相同，但没有氯化铯，并把1.0M的蔗糖的浓度改为30g/l)，并在25℃下生长3天或3天以上。用由COVE2平皿培养物切成的约为1cm的琼脂块接种盛在150ml烧瓶里的25ml FP1培养基(5％大豆粉、5％葡萄糖、2％ K2HPO4、0.2％ CaCl2、0.2％MgSO4·7H2O和0.1％Pluronic acid(BASF))等分试样，并在30℃、振荡(150rpm)下培养6天。离心后回收上清液样品，并进行以下SDS-PAGE分析。将每种上清液20μl与10μlSDS-PAGE样品缓冲液(1ml 0.5M Tris pH＝6.8、0.8ml甘油、1.6ml 10％ SDS、0.4ml 0.8M二硫苏糖醇、0.2ml 1％溴酚蓝)、2μl溶于异丙醇中的2％PMSF(Sigma)和2μl甘油混合。上述样品在沸水浴中放4分钟，并取每种样品40μl在10-27％聚丙烯酰胺凝胶(Novex)上电泳。按照标准方法，用考马斯染料对上述凝胶进行染色和脱色.经测定，类胰蛋白酶蛋白酶的表达水平≥0.5g/l。
10.酶分析
10.1 Carezyme
缓冲剂：磷酸钠(50mM，pH7.0)
底物：AZCL-HE纤维素(Megazyme)，2mg/ml缓冲液。
酶标准：将100mg Carezyme标准(10,070 ECu/g)溶于1ml缓冲液中，并在-20℃下保存。在用于酶分析之前，用缓冲液稀释上述储液(1∶100)。试验的范围为0.5-5.0ECU/ml。采用650，000ECU/g Carezyme转换因子。
将底物溶液(990μl)加至24孔微量滴定板的样品孔中。将10μl Carezyme样品(在缓冲液中稀释，以产生0.5-10E CU/ml的活性)加进上述底物中。在45℃下培养30分钟以进行反应，把上清液转移到96孔微量滴定板上，并测量在650nm处的光吸收。
10.2 Lipolase分析
缓冲液：0.1M MOPS，pH7.5，含有4mM CaCl2。
底物：将10ml丁酸对硝基苯酯(pNB)溶于1ml DMSO中；将4ml缓冲液加进溶解在DMSO中的底物里
*储液浓度＝11.5mM，溶于20％DMSO中
酶标准：以1000LU/ml的浓度把Lipolase(23,100LU/g)溶于50％甘油中，并在-20℃下保存。在试验之前以1∶100的比例将该储液稀释于缓冲液中。试验范围为0.125-3.0LU/ml。
将100μl pNB储液加进100μl经适当稀释的酶样品中。在25℃下用5分钟时间测405nm处的活性(mOD/分钟)。
10.3 SP387分析
在使用之前，通过把溶于二甲亚砜中的0.2M L-BAPNA(Sigma B3133)储液(冰冻保存)在缓冲液(0.01M谷氨酸二甲酯(Sigma)、0.2M硼酸和0.002M CaCl2，用NaOH把pH调至6.5)稀释为0.004M而制备L-BAPNA底物。对1μl培养物进行离心(14500×g，10分钟)。将100μl稀释过的培养物上清液等分试样加至96孔微量滴定板中的100μl底物中。采用一台ELISA计数器，在25℃温度下用5分钟时间以30秒的间隔测定405nm处的光吸收变化。结果是参比纯化的SP387标准计算出来的。
11. Carezyme的表达
纯化23个pDM151转化体，在摇瓶里的大豆/葡萄糖培养基上培养，并于9天之后检验Carezyme活性(见下面的表1)。4个转化体以大约50-100mg/L的水平表达Carezyme。将转化体pDM151-4在小型发酵罐中培养，采用生产SP387时所使用的条件(见9)。7天后，出现大约6.0g/L的Carezyme。以7天计，Carezyme中含有高于90％的分泌性蛋白(图8A)。根据SDS凝胶电泳测得Carezyme含有高于90％的分泌性蛋白(图8B)。
表I
转化体 ECU/ml mg/L
pDM151.3-4 58.2 90
pDM151.3-5 0 0
pDM151.3-6 0 0
pDM151.3-10 0 0
pDM151.3-11 2.46 4
pDM151.3-12 0 0
pDM151.3-13 12.2 19
pDM151.3-14 47.3 73
pDM151.3-15 22.7 35
pDM151.3-16 0 0
pDM151.3-17 0 0
pDM151.3-18 0 0
pDM151.3-19 0 0
pDM151.3-21 0 0
pDM151.3-22 43.7 67
pDM151.3-23 1.25 2
pDM151.3-24 17.8 27
pDM151.3-25 38 58
pDM151.3-26 0 0
pDM151.3-27 10.5 16
pDM151.3-28 49.3 76
pDM151.3-29 19.8 30
pDM151.3-30 22.7 35
12. Lipolase的表达
纯化15个pDM155转化体，在盛于摇瓶里的大豆/葡萄糖培养基中培养，并于9天之后检验Lipolase活性(表2)。
表II
转化体 LU/ml mg/ml
pDM155-1 669 167
pDM155-2 45.2 11
pDM155-3 180 45
pDM155-4 0 0
pDM155-5 55.4 14
pDM155-6 116 29
pDM155-7 704 176
pDM155-8 214 54
pDM155-9 17.1 4
pDM155-10 712 178
pDM155-11 511 128
pDM155-12 0 0
pDM155-13 0 0
pDM155-14 0 0
pDM155-15 153 38
pDM155-16 0 0
pDM155-17 0 0
pDM155-18 0 0
pDM155-19 129 32
pDM155-20 378 95
pDM155-21 216 54
4个转化体以大约100-200mg/l的水平(基于pNB分析)表达Lipolase。在小型发酵罐中培养pDM155-10，采用生产SP387时所使用的条件(见9)。7天后，出现大约2.0g/l的Lipolase(图8A)。根据SDS凝胶电泳测得Lipolase含有90％以上的分泌性蛋白(图8B)。
7.微生物的保藏
已将下列生物材料保存在NRRL(Agricultural ResearchService Patent Culture Collection)，Northern Regional ResearchCenter，1815，University Street，Peoria，Illinois，61604，USA.
菌株 入藏号 保藏日期
带有pJRoy6的大肠杆菌 NRRL B-21285 6/20/94
带有的大肠杆菌 NRRL B-21418 3/10/95
带有pDM151的大肠杆菌 NRRL B-21419 3/10/95
带有pDM155的大肠杆菌 NRRL B-21420 3/10/95
上述菌株在这样的条件下保藏：确保在该专利申请期间，由专利商标局长指定的人可以获得其培养物，是按照37C.R.R§1.14和35U.S.C.§122和布达佩斯条约的条件确定的。该保藏物代表每种保藏菌株的生物学纯培养物。可按照向其提交了该申请的副本或后续申请的外国国家的专利法要求，向其提供保藏物。不过，应当明白，可以得到保藏物并不意味着可以实施本发明而使由政府授予的专利权丧失效力。
在这里所披露和要求保护的本发明，并不局限于具体实施方案所限定的范围，因为这些实施方案只是用于说明本发明的几个方面的。任何类似实施方案都包括在本发明范围之内.实际上，通过以上说明，除本文所披露的内容外，对本发明所做的各种改进对本领域技术人员来说都是显而易见的。这样的改进同样落在所附权利要求的范围内。
这里所引用的各对比文件所披露的内容的整体，被作为本申请的参考。
序列表
(1)一般资料：
(I)申请人：
(A)名称：Novo Nordisk Biotech，Inc.
(B)街道：1445 Drew Avenue，Ste.105
(C)城市：Davis
(D)州：California
(E)国家：US
(F)邮政编码：95616-4880
(G)电话：(916)757-8100
(H)传真：(916)758-0317
(ii)发明名称：非毒性、非产毒性、非致病性镰孢属表达系统及所用启动子和终止子
(iii)序列数：16
(iv)有关地址：
(A)地址：Novo Nordisk of North America，Inc.
(B)衔道：405 Lexington Avenue，64th Floor
(C)城市：New York
(D)州：New York
(E)国家：USA
(F)邮编：10174-6401
(v)计算机可读形式：
(A)介质类型：软盘
(B)计算机：IBM PC兼容机
(C)操作系统：PC-DOS/MS-DOS
(D)软件：Patent IN Release#1.0，Version#1.30
(vi)本申请数据：
(A)申请号：待定
(B)申请日：1995年6月15日
(C)分类号：(vii)优先权申请资料(A)申请号：US08/269,449(B)申请日：1994年6月30日(vii)优先权申请资料(A)申请号：US 08/404,678(B)申请日：1995年3月15日(viii)律师/代理人信息(A)姓名：Agris Dr.，Cheryl H.(B)登记号：34,086(C)参考/案卷号：4216.204-WO(ix)通讯信息：(A)电话：212-867-0123(B)传真：212-878-9655(2)SEQ ID NO：1的资料(i)序列特征：(A)长度：30bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：1TGCGGATCCA TGGTCAAGTT CGCTTCCGTC                      30(2)SEQ ID NO：2的资料(i)序列特征：(A)长度：30bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：2GACCTCGAGT TAAGCATAGG TGTCAATGAA                      30(2)SEQ ID NO：3的资料(i)序列特征：(A)长度：998bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：3：ATCATCAACC   ACTCTTCACT   CTTCAACTCT   CCTCTCTTGG   ATATCTATCT   CTTCACCATG     60GTCAAGTTCG   CTTCCGTCGT   TGCACTTGTT   GCTCCCCTGG   CTGCTGCCGC   TCCTCAGGAG    120ATCCCCAACA   TTGTTGGTGG   CACTTCTGCC   AGCGCTGGCG   ACTTTCCCTT   CATCGTGAGC    180ATTAGCCGCA   ACGGTGGCCC   CTGGTGTGGA   GGTTCTCTCC   TCAACGCCAA   CACCGTCTTG    240ACTGCTGCCC   ACTGCGTTTC   CGGATACGCT   CAGAGCGGTT   TCCAGATTCG   TGCTGGCAGT    300CTGTCTCGCA   CTTCTGGTGG   TATTACCTCC   TCGCTTTCCT   CCGTCAGAGT   TCACCCTAGC    360TACAGCGGAA   ACAACAACGA   TCTTGCTATT   CTGAAGCTCT   CTACTTCCAT   CCCCTCCGGC    420GGAAACATCG   GCTATGCTCG   CCTGGCTGCT   TCCGGCTCTG   ACCCTGTCGC   TGGATCTTCT    480GCCACTGTTG   CTGGCTGGGG   CGCTACCTCT   GAGGGCGGCA   GCTCTACTCC   CGTCAACCTT    540CTGAAGGTTA   CTGTCCCTAT   CGTCTCTCGT   GCTACCTGCC   GAGCTCAGTA   CGGCACCTCC    600GCCATCACCA   ACCAGATGTT   CTGTGCTGGT   GTTTCTTCCG   GTGGCAAGGA   CTCTTGCCAG    660GGTGACAGCG   GCGGCCCCAT   CGTCGACAGC   TCCAACACTC   TTATCGGTGC   TGTCTCTTGG    720GGTAACGGAT   GTGCCCGACC   CAACTACTCT   GGTGTCTATG   CCAGCGTTGG   TGCTCTCCGC    780TCTTTCATTG   ACACCTATGC   TTAAATACCT   TGTTGGAAGC   GTCGAGATGT   TCCTTGAATA    840TTCTCTAGCT   TGAGTCTTGG   ATACGAAACC   TGTTTGAGAA   ATAGGTTTCA   ACGAGTTAAG    900AAGATATGAG   TTGATTTCAG   TTGGATCTTA   GTCCTGGTTG   CTCGTAATAG   AGCAATCTAG    960ATAGCCCAAA   TPGAATATGA   AATTTGATGA   AAATATTC                                998(2)SEQ ID NO：4的资料：(i)序列特征(A)长度：248个氨基酸(B)类型：氨基酸(C)链型：单链(D)拓扑学：线性(ix)特征：(A)名称/关键词：蛋白质(B)位置：1..224(ix)特征：(A)名称/关键词：肽(B)位置：-24..0(D)其它资料：/product＝ “OTHER”/note＝“Label＝pre-propeptide”(xi)序列表述：SEQ ID NO：4：Met Val Lys Phe Ala Ser Val Val Ala Leu Val Ala Pro Leu Ala Ala
            -20                 -15                 -10Ala Ala Pro Gln Glu Ile Pro Asn Ile Val Gly Gly Thr Ser Ala Ser
        -5                  1                5Ala Gly Asp Phe Pro Phe Ile Val Ser Ile Ser Arg Asn Gly Gly Pro
10                  15                  20Trp Cys Gly Gly Ser Leu Leu Asn Ala Asn Thr Val Leu Thr Ala Ala25                  30                  35                  40His Cys Val Ser Gly Tyr Ala Gln Ser Gly Phe Gln Ile Arg Ala Gly
            45                  50                  55Ser Leu Ser Arg Thr Ser Gly Gly Ile Thr Ser Ser Leu Ser Ser Val
        60                  65                  70Arg Val His Pro Ser Tyr Ser Gly Asn Asn Asn Asp Leu Ala Ile Leu
    75                  80                  85Lys Leu Ser Thr Ser Ile Pro Ser Gly Gly Asn Ile Gly Tyr Ala Arg
90                  95                  100Leu Ala Ala Ser Gly Ser Asp Pro Val Ala Gly Ser Ser Ala Thr Val105                 110                 115                 120Ala Gly Trp Gly Ala Thr Ser Glu Gly Gly Ser Ser Thr Pro Val Asn
            125                 130                 135Leu Leu Lys Val Thr Val Pro Ile Val Ser Arg Ala Thr Cys Arg Ala
        140                 145                 150Gln Tyr Gly Thr Ser Ala Ile Thr Asn Gln Met Phe Cys Ala Gly Val
    155                 160                 165Ser Ser Gly Gly Lys Asp Ser Cys Gln Gly Asp Ser Gly Gly Pro Ile
170                 175                 180Val Asp Ser Ser Asn Thr Leu Ile Gly Ala Val Ser Trp Gly Asn Gly185                 190                 195                 200Cys Ala Arg Pro Asn Tyr Ser Gly Val Tyr Ala Ser Val Gly Ala Leu
            205                 210                 215Arg Ser Phe Ile Asp Thr Tyr Ala
        220(2)SEQ ID NO：5的资料(i)序列特征：(A)长度：1206bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：5GAATTCTTAC   AAACCTTCAA   CAGTGGAGAC   TTCCGACACG   ACATATCGAT   CCTTTGAAGA        60TACGGTGAGC   GTCAGATCAT   GAATTTCATA   CATCCTCACG   TCCTTCCTCT   TTCAAACTAT       120GCAAAGTCCT   TCTAGTACCT   CCCAAAACTT   GATTTACGCG   CTCTCCAATC   AAAAGTACCT       180TCCAAAAGTG   ATCTACCTCA   GCTCTAGATC   AGGGCACCTA   TTCGCAAAGA   TCTACAAGCT       240GAACTAGTAA   GCATAGCGGG   AGAATATCCC   ACATCATTCG   AGAAGGCCTT   CGTATTAGAC       300CTAGTGGGAT   CGACAGAAAA   GATAAGACGG   AGATAGATGC   TATGTTTGGA   AGGTAGGGGA       360TGGAATAGGA   TGCAACAGGT   ATTGGCATAA   GCGATGCAAT   AGGTGCATCT   AGAAACTAGG       420TGACAGACTG   GCCACAGAGG   TGTATCCTAT   GCAGGTCGAT   GCGTGCGTTA   TCGCAGGGCT       480GCTATTGCGT   GGTGGTGGCT   ACAAAAGTTC   TATGTGGTTT   CCAGTTTCAG   AATATTGGGC       540CATTGTGATT   GATGGCGCAT   GACCGAATTA   TAGCAGTGAA   CCCCGCCCAG   AGTAGTAGTG       600CAGATGCGCT   TTGATGCTTG   GCGATTCCTC   GGGCTAAATA   ACTCCGGTTG   GTCTGTAGAA       660TGCTGACGCG   ATGATCCTTC   GGCATTAATC   GTAGATCTTG   GGGGGGGATA   AGCCGATCAA       720AGACACACTG   TAGATCAGCT   CTTCGATGAC   TCTTACCAGC   TTTATAATAA   CATTCATCTT       780GAACGTCTTT   TTCGTCCAGT   GTTTACCTTT   CGTCCTATTT   ATCCGTCATA   TCCACAGTGT       840TATTGGCGAT   AGAGTTATCG   ACTTTCCTCA   TCGGGATACT   GGCCCCTGCT   GCCAAGGGCC       900TTATATGCCG   ATCACTTTCA   CGGGAGCATG   ATAAGGTTAA   TGCTTCTTCT   GAATGCCGAA       960CTAGACTACG   GAACAACGGA   GCTTAGTACC   AGAAAGGCAG   GTACGCCTAT   TCGCAAACTC      1020CGAAGATACA   ACCAAGCAAG   CTTATCGCGG   GATAGTAACC   AGAGAGGCAG   GTAAGAAGAC      1080ACAACAACAT   CCATAGCTAT   GTAGATTCTC   GAATATAAAA   GGACCAAGAT   GGACTATTCG      1140AAGTAGTCTA   TCATCAACCA   CTCTTCACTC   TTCAACTCTC   CTCTCTTGGA   TATCTATCTC      1200TTCACC                                                                           1206(2)SEQ ID NO：6的资料：(i)序列特征(A)长度：1188bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：6：TAAATACCTT GTTGGAAGCG TCGAGATGTT CCTTGAATAT TCTCTAGCTT GAGTCTTGGA        60TACGAAACCT GTTTGAGAAA TAGGTTTCAA CGAGTTAAGA AGATATGAGT TGATTTCAGT       120TGGATCTTAG TCCTGGTTGC TCGTAATAGA GCAATCTAGA TAGCCCAAAT TGAATATGAA       180ATTTGATGGA AATATTCATT TCGATAGAAG CAACGTGAAA TGTCTAGCAG GACGAAAAGT       240AGATCAAGGC TGTTATGTTC CCCGACCAAC CTACCTTGAT GTCAGTCTGC GAGTCGTGTG       300CAGTGACCCA GAATGATGGA TTGACTTGGA CATTTTCTGT CTATGAAGTA TTATGAACAT       360GAATATCGTT TCCTCATTAT CTATGTTGGC AGCCTAAAGT TTTACCATAT AGCTAGCAAT       420CAGTCAAGTA TCTGCGTATG AAGGGTTGTT AAGCCAGGAC GGTATCAGCG TTGAATATTT       480AAAGAATGAT ATGAGATAAT CAACATTGAC ATGATAAAAG AAAAGGGGAA ACAAATTGTG       540CATATAGTAA AGACTTCAGG TCGACCCCTC AATAGACATA TGCGAACCGA AAACCAACAG       600GATACAATTT ATAGATAAGT ATAACTACAG TTATCTGTCT GCCGAACAAA TACTCTTTTG       660TGAAACAAAT GAAGAGTACA TAAGCTACAG TTCCTCAGTA GGAACATCCT TTACAATAAC       720TCCCTTGACT TCCTTCAGCT TCTCAATAGC CTCCAAAGTC ATCGGTCTGC CATCAAGGCA       780CGTCAGCTCT GGTGTAGCAT ACAGCAGTGC CATACTTACG GAGGATAGGA AGTGGGAGGA       840ATCGTTCGTG TCTGCCTCCA AAAATCGACA CCAGTGTCCT TTTTGACGAT ACTGATATGG       900TGGTAAGCTT GGGAGTCTAT TGTTGACGTT GCATCACTTA CTTAAGCACG GTTTCATTCC       960TCTGCTGATA GTCCTCCAAC TTCTCGAAGT CGTAAACGAT GGCCTATAGT ATCTTATTGA      1020GAAATATGTC TTCTCAGAAA ATTATATCTT GTTTACCTTT CGGTCCGCCA TGGGTGCTAA      1080AACTGCTGGG AAATTCAAAA GCGCAGCACA AGCAGCAAGA GTGATGGGCA CAACGTGATA      1140TGTTGATAAA AGCATCAGTA TCGATAAGTT CCACTCAGAA ACCTGCAG                   1188(2)SEQ ID NO：7的资料(i)序列特征：(A)长度：1060bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(ix)特征：(A)名称/关键词：CDS(B)位置：10..924(ix)特征：(A)名称/关键词：：mat-peptide(B)位置：73..924(ix)特征：(A)名称/关键词：sig-peptide(B)位置：10..72(xi)序列表述：SEQ ID NO：7：GGATCCAAG ATG CGT TCC TCC CCC CTC CTC CCG TCC GCC GTT GTG GCC      48
      Met Arg Ser Ser Pro Leu Leu Pro Ser Ala Val Val Ala
      -21 -20                  -15                -10GCC CTG CCG GTG TTG GCC CTT GCC GCT GAT GGC AGG TCC ACC CGC TAC    96Ala Leu Pro Val Leu Ala Leu Ala Ala Asp Gly Arg Ser Thr Arg Tyr
        -5                    1               5TGG GAC TGC TGC AAG CCT TCG TGC GGC TGG GCC AAG AAG GCT CCC GTG   144Trp Asp Cys Cys Lys Pro Ser Cys Gly Trp Ala Lys Lys Ala Pro Val
 10                  15                  20AAC CAG CCT GTC TTT TCC TGC AAC GCC AAC TTC CAG CGT ATC ACG GAC   192Asn Gln Pro Val Phe Ser Cys Asn Ala Asn Phe Gln Arg Ile Thr Asp25                  30                  35                  40TTC GAC GCC AAG TCC GGC TGC GAG CCG GGC GGT GTC GCC TAC TCG TGC   240Phe Asp Ala Lys Ser Gly Cys Glu Pro Gly Gly Val Ala Tyr Ser Cys
             45                  50                  55GCC GAC CAG ACC CCA TGG GCT GTG AAC GAC GAC TTC GCG CTC GGT TTT   288Ala Asp Gln Thr Pro Trp Ala Val Asn Asp Asp Phe Ala Leu Gly Phe
         60                  65                  70GCT GCC ACC TCT ATT GCC GGC AGC AAT GAG GCG GGC TGG TGC TGC GCC   336Ala Ala Thr Ser Ile Ala Gly Ser Asn Glu Ala Gly Trp Cys Cys Ala
     75                  80                  85TGC TAC GAG CTC ACC TTC ACA TCC GGT CCT GTT GCT GGC AAG AAG ATG   384Cys Tyr Glu Leu Thr Phe Thr Ser Gly Pro Val Ala Gly Lys Lys Met
 90                  95                 100GTC GTC CAG TCC ACC AGC ACT GGC GGT GAT CTT GGC AGC AAC CAC TTC   432Va1 Val Gln Ser Thr Ser Thr Gly Gly Asp Leu Gly Ser Asn His Phe105                 110                 115                 120GAT CTC AAC ATC CCC GGC GGC GGC GTC GGC ATC TTC GAC GGA TGC ACT   480Asp Leu Asn Ile Pro Gly Gly Gly Val Gly Ile Phe Asp Gly Cys Thr
            125                 130                 135CCC CAG TTC GGC GGT CTG CCC GGC CAG CGC TAC GGC GGC ATC TCG TCC      528Pro Gln Phe Gly Gly Leu Pro Gly Gln Arg Tyr Gly Gly Ile Ser Ser
        140                 145                 150CGC AAC GAG TGC GAT CGG TTC CCC GAC GCC CTC AAG CCC GGC TGC TAC      576Arg Asn Glu Cys Asp Arg Phe Pro Asp Ala Leu Lys Pro Gly Cys Tyr
    155                 160                 165TGG CGC TTC GAC TGG TTC AAG AAC GCC GAC AAT CCG AGC TTC AGC TTC      624Trp Arg Phe Asp Trp Phe Lys Asn Ala Asp Asn Pro Ser Phe Ser Phe
170                 175                 180CGT CAG GTC CAG TGC CCA GCC GAG CTC GTC GCT CGC ACC GGA TGC CGC      672Arg Gln Val Gln Cys Pro Ala Glu Leu Val Ala Arg Thr Gly Cys Arg185                 190                 195                 200CGC AAC GAC GAC GGC AAC TTC CCT GCC GTC CAG ATC CCC TCC AGC AGC      720Arg Asn Asp Asp Gly Asn Phe Pro Ala Val Gln Ile Pro Ser Ser Ser
            205                 210                 215ACC AGC TCT CCG GTC AAC CAG CCT ACC AGC ACC AGC ACC ACG TCC ACC      768Thr Ser Ser Pro Val Asn Gln Pro Thr Ser Thr Ser Thr Thr Ser Thr
        220                 225                  230TCC ACC ACC TCG AGC CCG CCA GTC CAG CCT ACG ACT CCC AGC GGC TGC      816Ser Thr Thr Ser Ser Pro Pro Val Gln Pro Thr Thr Pro Ser Gly Cys
    235                 240                 245ACT GCT GAG AGG TGG GCT CAG TGC GGC GGC AAT GGC TGG AGC GGC TGC      864Thr Ala Glu Arg Trp Ala Gln Cys Gly Gly Asn Gly Trp Ser Gly Cys
250                 255                 260ACC ACC TGC GTC GCT GGC AGC ACT TGC ACG AAG ATT AAT GAC TGG TAC      912Thr Thr Cys Val Ala Gly Ser Thr Cys Thr Lys Ile Asn Asp Trp Tyr265                 270                 275                 280CAT CAG TGC CTG TAGACGCAGG GCAGCTTGAG GGCCTTACTG GTGGCCGCAA          964His Gln Cys LeuCGAAATGACA CTCCCAATCA CTGTATTAGT TCTTGTACAT AATTTCGTCA TCCCTCCAGG   1024GATTGTCACA TAAATGCAAT GAGGAACAAT GAGTAC                             1060(2)SEQ ID NO：8的资料(i)序列特征：(A)长度：305个氨基酸(B)类型：氨基酸(D)拓扑学：线性(ii)分子类型：蛋白质(xi)序列表述：SEQ ID NO：8：Met Arg Ser Ser Pro Leu Leu Pro Ser Ala Val Val Ala Ala Leu Pro-21 -20                 -15                 -10Val Leu Ala Leu Ala Ala Asp Gly Arg Ser Thr Arg Tyr Trp Asp Cys-5                    1               5                  10Cys Lys Pro Ser Cyg Gly Trp Ala Lys Lys Ala Pro Val Asn Gln Pro
         15                  20                  25Val Phe Ser Cys Asn Ala Asn Phe Gln Arg Ile Thr Asp Phe Asp Ala
     30                  35                  40Lys Ser Gly Cys Glu Pro Gly Gly Val Ala Tyr Ser Cys Ala Asp Gln
 45                  50                  55Thr Pro Trp Ala Val Asn Asp Asp Phe Ala Leu Gly Phe Ala Ala Thr60                  65                  70                  75Ser Ile Ala Gly Ser Asn Glu Ala Gly Trp Cys Cys Ala Cys Tyr Glu
            80                   85                  90Leu Thr Phe Thr Ser Gly Pro Val Ala Gly Lys Lys Met Val Val Gln
         95                 100                 105Ser Thr Ser Thr Gly Gly Asp Leu Gly Ser Asn His Phe Asp Leu Asn
    110                 115                 120Ile Pro Gly Gly Gly Val Gly Ile Phe Asp G1y Cys Thr Pro Gln Phe
125                 130                 135Gly Gly Leu Pro Gly Gln Arg Tyr Gly Gly Ile Ser Ser Arg Asn Glu140                 145                 150                 155Cys Asp Arg Phe Pro Asp Ala Leu Lys Pro Gly Cys Tyr Trp Arg Phe
            160                 165                 170Asp Trp Phe Lys Asn Ala Asp Asn Pro Ser Phe Ser Phe Arg Gln Val
        175                 180                 185Gln Cys Pro Ala Glu Leu Val Ala Arg Thr Gly Cys Arg Arg Asn Asp
    190                 195                 200Asp Gly Asn Phe Pro Ala Val Gln Ile Pro Ser Ser Ser Thr Ser Ser
205                 210                 215Pro Val Asn Gln Pro Thr Ser Thr Ser Thr Thr Ser Thr Ser Thr Thr220                 225                 230                 235Ser Ser Pro Pro Val Gln Pro Thr Thr Pro Ser Gly Cys Thr Ala Glu
            240                 245                 250Arg Trp Ala Gln Cys Gly Gly Asn Gly Trp Ser Gly Cys Thr Thr Cys
        255                 260                 265Val Ala Gly Ser Thr Cys Thr Lys Ile Asn Asp Trp Tyr His Gln Cys
    270                 275                 280Leu(2)SEQ ID NO：9的资料：(i)序列特征：(A)长度：876bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：9：ATGAGGAGCT   CCCTTGTGCT   GTTCTTTGTC   TCTGCGTGGA   CGGCCTTGGC   CAGTCCTATT        60CGTCGAGAGG   TCTCGCAGGA   TCTGTTTAAC   CAGTTCAATC   TCTTTGCACA   GTATTCTGCA       120GCCGCATACT   GCGGAAAAAA   CAATGATGCC   CCAGCTGGTA   CAAACATTAC   GTGCACGGGA       180AATGCCTGCC   CCGAGGTAGA   GAAGGCGGAT   GCAACGTTTC   TCTACTCGTT   TGAAGACTCT       240GGAGTGGGCG   ATGTCACCGG   CTTCCTTGCT   CTCGACAACA   CGAACAAATT   GATCGTCCTC       300TCTTTCCGTG   GCTCTCGTTC   CATAGAGAAC   TGGATCGGGA   ATCTTAACTT   CGACTTGAAA       360GAAATAAATG   ACATTTGCTC   CGGCTGCAGG   GGACATGACG   GCTTCACTTC   GTCCTGGAGG       420TCTGTAGCCG   ATACGTTAAG   GCAGAAGGTG   GAGGATGCTG   TGAGGGAGCA   TCCCGACTAT       480CGCGTGGTGT   TTACCGGACA   TAGCTTGGGT   GGTGCATTGG   CAACTGTTGC   CGGAGCAGAC       540CTGCGTGGAA   ATGGGTATGA   TATCGACGTG   TTTTCATATG   GCGCCCCCCG   AGTCGGAAAC       600AGGGCTTTTG   CAGAATTCCT   GACCGTACAG   ACCGGCGGAA   CACTCTACCG   CATTACCCAC       660ACCAATGATA   TTGTCCCTAG   ACTCCCGCCG   CGCGAATTCG   GTTACAGCCA   TTCTAGCCCA       720GAGTACTGGA   TCAAATCTGG   AACCCTTGTC   CCCGTCACCC   GAAACGATAT   CGTGAAGATA       780GAAGGCATCG   ATGCCACCGG   CGGCAATAAC   CAGCCTAACA   TTCCGGATAT   CCCTGCGCAC       840CTATGGTACT   TCGGGTTAAT   TGGGACATGT   CTTTAG                                     876(2)SEQ ID NO：10的资料(i)序列特征：(A)长度：291个氨基酸(B)类型：氨基酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：10：Met Arg Ser Ser Leu Val Leu Phe Phe Val Ser Ala Trp Thr Ala Leu1               5                   10                  15Ala Ser Pro Ile Arg Arg Glu Val Ser Gln Asp Leu Phe Asn Gln Phe
        20                  25                  30Asn Leu Phe Ala Gln Tyr Ser Ala Ala Ala Tyr Cys Gly Lys Asn Asn
    35                  40                  45Asp Ala Pro Ala Gly Thr Asn Ile Thr Cys Thr Gly Asn Ala Cys Pro
50                  55                  60Glu Val Glu Lys Ala Asp Ala Thr Phe Leu Tyr Ser Phe Glu Asp Ser65                  70                  75                  80Gly Val Gly Asp Val Thr Gly Phe Leu Ala Leu Asp Asn Thr Asn Lys
            85                  90                  95Leu Ile Val Leu Ser Phe Arg Gly Ser Arg Ser Ile Glu Asn Trp Ile
        100                 105                 110Gly Asn Leu Asn Phe Asp Leu Lys Glu Ile Asn Asp Ile Cys Ser Gly
    115                 120                 125Cys Arg Gly His Asp Gly Phe Thr Ser Ser Trp Arg Ser Val Ala Asp
130                 135                 140Thr Leu Arg Gln Lys Val Glu Asp Ala Val Arg Glu His Pro Asp Tyr145                 150                 155                 160Arg Val Val Phe Thr Gly His Ser Leu Gly Gly Ala Leu Ala Thr Val
            165                 170                 175Ala Gly Ala Asp Leu Arg Gly Asn Gly Tyr Asp Ile Asp Val Phe Ser
        180                 185                 190Tyr Gly Ala Pro Arg Val Gly Asn Arg Ala Phe Ala Glu Phe Leu Thr
    195                 200                 205Val Gln Thr Gly Gly Thr Leu Tyr Arg Ile Thr His Thr Asn Asp Ile
210                 215                 220Val Pro Arg Leu Pro Pro Arg Glu Phe Gly Tyr Ser His Ser Ser Pro225                 230                 235                 240Glu Tyr Trp Ile Lys Ser Gly Thr Leu Val Pro Val Thr Arg Asn Asp
            245                 250                 255Ile Val Lys Ile Glu Gly Ile Asp Ala Thr Gly Gly Asn Asn Gln Pro
        260                 265                 270Asn Ile Pro Asp Ile Pro Ala His Leu Trp Tyr Phe Gly Leu Ile Gly
    275                 280                 285Thr Cys Leu
290(2)SEQ ID NO：11的资料(i)序列特征：(A)长度：42bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：11：GCACACCATG GTCGCTGGAT CCATACCTTG TTGGAAGCGT CG                  42(2)SEQ ID NO：12的资料(i)序列特征(A)长度：56bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：12：ATCGGAGCAT GCGGTACCGT TTAAACGAAT TCAGGTAAAC AAGATATAAT TTTCTG   56(2)SEQ ID NO：13的资料(i)序列特征(A)长度：44bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：13：CTCTTGGATA TCTATCTCTT CACCATGCGT TCCTCCCCCC TCCT                44(2)SEQ ID NO：14的资料(i)序列特征(A)长度：20bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：14：CAATAGAGGT GGCAGCAAAA                                         20(2)SEQ ID NO：15的资料(i)序列特征：(A)长度：25bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：15：ATCTATCTCT TCACCATGAG GAGCT                                   25(2)SEQ ID NO：16的资料(i)序列特征(A)长度：21bp(B)类型：核酸(C)链型：单链(D)拓扑学：线性(xi)序列表述：SEQ ID NO：16：TAGATAGAGA AGTGGTACTC C                                       21

Claims (28)

1.一种非毒性、非产毒性、非致病性重组镰孢属(Fusarium)宿主细胞，它包括一个与一个启动子可操纵连接的编码一种异源蛋白的核酸序列。
2.如权利要求1的宿主细胞，其中，所述镰孢菌是禾本科镰孢(Fusarium graminearum)。
3.如权利要求1的宿主细胞，其中，所述禾本科镰孢具有ATCC20334的鉴定特征。
4.如权利要求1的宿主细胞，其中，所述异源蛋白是一种真菌蛋白。
5.如权利要求1的宿主细胞，其中，所述异源蛋白是一种分泌性蛋白。
6.如权利要求1的宿主细胞，其中，所述异源蛋白是一种真菌酶。
7.如权利要求6的宿主细胞，其中，所述真菌酶选自过氧化氢酶、漆酶、酚氧化酶、氧化酶、氧化还原酶、纤维素酶、木聚糖酶、过氧化物酶、脂肪酶、水解酶、酯酶、角质酶、一种蛋白酶、氨肽酶、羧肽酶、肌醇六磷酸酶、裂合酶、溶果胶酶、淀粉酶、葡糖淀粉酶、α-半乳糖苷酶、β-半乳糖苷酶、α-葡糖苷酶、β-葡糖苷酶、甘露糖苷酶、异构酶、转化酶、转移酶、核糖核酸酶、壳多糖酶和脱氧核糖核酸酶。
8.如权利要求6的宿主细胞，其中，所述真菌酶是一种蛋白酶。
9.如权利要求6的宿主细胞，其中，所述真菌酶是一种碱性蛋白酶。
10.如权利要求9的宿主细胞，其中，所述碱性蛋白酶是尖镰孢(Fusarium oxysporum)类胰蛋白酶蛋白酶。
11.如权利要求10的宿主细胞，其中，所述尖镰孢类胰蛋白酶蛋白酶的氨基酸序列如SEQ ID NO：4所示。
12.如权利要求6的宿主细胞，其中，所述真菌酶是一种内切葡聚糖酶或其变体。
13.如权利要求14的宿主细胞，其中，所述内切葡聚糖酶的氨基酸序列如SEQ ID NO：8所示。
14.如权利要求6的宿主细胞，其中，所述真菌酶是1，3脂肪酶或其变体。
15.如权利要求12的宿主细胞，其中，所述1，3脂肪酶的氨基酸序列如SEQ ID NO：10所示。
16.如权利要求1的宿主细胞，其中，所述异源蛋白选自激素，生长因子和受体。
17.如权利要求1的宿主细胞，其中，所述启动子是一种真菌启动子。
18.如权利要求17的宿主细胞，其中，所述启动子选自来自构巢曲霉(A.nidulans)amdS的启动子。
19.如权利要求17的宿主细胞，其中，所述真菌启动子来自一个编码尖镰孢类胰蛋白酶蛋白酶的基因或其片段，该片段具有基本上与所述序列相同的启动子活性。
20.如权利要求19的宿主细胞，其中，所述启动子序列如SEQ IDNO：5所示。
21.如权利要求1的宿主细胞，它还包括一个选择标记。
22.如权利要求13的宿主细胞，其中，所述标记选自arg B、trpC、pyrG、amdS、niaD和hygB。
23.如权利要求1的宿主细胞，它还包括一个终止子。
24.如权利要求23的宿主细胞，其中，所述终止子来自一个编码尖镰孢类胰蛋白酶蛋白酶的基因或其片段，该片段具有基本上与所述序列相同的终止子活性。
25.如权利要求24的宿主细胞，其中，所述终止子序列如SEQ IDNO：6所示。
26.一种生产目的蛋白质的方法，它包括培养一种非毒性、非产毒性、非致病性重组镰孢属宿主细胞，该宿主细胞包括一个与一个启动子可操纵连接的编码所述蛋白质的核酸序列，以及分离所述蛋白质。
27.一种来自一个编码尖镰孢类胰蛋白酶蛋白酶的基因或其片段的启动子序列，所述片段具有基本上与所述序列相同的启动子活性，其中，该启动子的序列如SEQ ID NO：5所示。
28.一种来自一个编码尖镰孢类胰蛋白酶蛋白酶的基因或其片段的终止子序列，所述片段具有基本上与所述序列相同的终止子活性，其中，该终止子的序列如SEQ ID NO：6所示。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1318595C (zh) * 1999-01-13 2007-05-30 诺沃奇梅兹有限公司 在缺乏环己缩酚肽的细胞中制备多肽的方法

Families Citing this family (683)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69736606T2 (de) * 1996-07-24 2007-09-20 Meiji Seika K.K. Cellulase und Cellulase-Präperation, die dieselbe enthält
US7883872B2 (en) * 1996-10-10 2011-02-08 Dyadic International (Usa), Inc. Construction of highly efficient cellulase compositions for enzymatic hydrolysis of cellulose
US5811381A (en) * 1996-10-10 1998-09-22 Mark A. Emalfarb Cellulase compositions and methods of use
DE69840230D1 (de) 1997-05-16 2009-01-02 Novozymes Inc Polypeptide mit prolyldipeptidylaminopeptidase-aktivität und dafür kodierende nukleinsäuren
EP1078081B1 (en) * 1998-05-20 2008-05-14 Novozymes, Inc. Methods for producing heterologous polypeptides in trichothecene-deficient filamentous fungal mutant cells
DK1117808T3 (da) * 1998-10-06 2005-04-25 Mark Aaron Emalfarb Transformaationssystem inden jfjor området filamentöse svampeværter: I chrysosporium
DE69932345T2 (de) 1998-10-26 2007-07-19 Novozymes A/S Erstellung und durchmusterung von interessierenden dna-banken in zellen von filamentösen pilzen
US6361973B1 (en) 1999-03-22 2002-03-26 Novozymes Biotech, Inc. Promoters for expressing genes in a fungal cell
CN100482801C (zh) * 1999-03-22 2009-04-29 诺沃奇梅兹有限公司 用于在真菌细胞中表达基因的启动子
EP2206786A1 (en) 1999-08-31 2010-07-14 Novozymes A/S Novel proteases and variants thereof
ES2327606T3 (es) 2000-01-10 2009-11-02 Maxygen Holdings Ltd Conjugados de g-csf.
DE60138364D1 (de) 2000-02-11 2009-05-28 Bayer Healthcare Llc Gerinnungsfaktor vii oder viia konjugate
CN1425068B (zh) 2000-03-14 2011-05-18 诺维信公司 在制备多肽的方法中有效的真菌转录激活因子
EP2281878A1 (en) 2000-06-26 2011-02-09 Novozymes A/S Lipolytic enzyme
WO2002016547A2 (en) 2000-08-21 2002-02-28 Novozymes A/S Subtilase enzymes
JP5230889B2 (ja) 2000-09-05 2013-07-10 ノボザイムス アクティーゼルスカブ リポキシゲナーゼ
YU48703A (sh) 2001-02-27 2006-05-25 Maxygen Aps Novi interferonu beta-slični molekuli
DE60234822D1 (de) 2001-04-20 2010-02-04 Novozymes As Lipoxygenase-varianten und ihre verwendung
WO2003000941A2 (en) 2001-06-26 2003-01-03 Novozymes A/S Polypeptides having cellobiohydrolase i activity and polynucleotides encoding same
DE10207702C1 (de) * 2002-02-22 2003-08-28 Albrecht Gmbh Einstellbare Gelenkorthese
US8148155B2 (en) 2002-04-22 2012-04-03 Novozymes, Inc. Methods for increasing homologous recombination of a nucleic acid sequence
DK1499733T3 (da) 2002-04-22 2010-07-12 Novozymes Inc Fremgangsmåder til fremstilling af varianter af en DNA-sekvens i trådformige svampe
WO2004020612A1 (en) 2002-08-30 2004-03-11 Novozymes Biotech, Inc. Methods for producing mammalian trypsins
JP4629439B2 (ja) * 2002-09-24 2011-02-09 ノボザイムス，インコーポレイティド キモトリプシン活性を有する微生物トリプシン変異体及びそれをコードする核酸
DE60335640D1 (de) 2002-10-01 2011-02-17 Novozymes As Polypeptide der gh-61-familie
CN101497908B (zh) 2002-11-18 2014-05-21 诺维信股份有限公司 用于在真菌细胞中表达基因的启动子变体
EP1578964B2 (en) 2002-12-20 2013-09-04 Novozymes A/S Polypeptides having cellobiohydrolase ii activity and polynucleotides encoding same
ATE441664T1 (de) 2003-03-31 2009-09-15 Novozymes Inc Verfahren zur produktion biologischer substanzen in enzymmangelmutanten von aspergillus niger
NZ542924A (en) 2003-04-28 2008-01-31 Novozymes As Method of producing a phospholipase which comprises processing an expressed fungal peptide so as to cleave off a peptide from the C- terminal end and/or a peptide from the N-terminal end to obtain a core peptide
EP1622921B1 (en) 2003-05-02 2010-06-16 Novozymes Inc. Variants of beta-glucosidases
EP1639107B1 (en) 2003-06-19 2013-08-14 Novozymes A/S Improved proteases and methods for producing them
ATE469214T1 (de) 2003-06-19 2010-06-15 Novozymes As Proteasen
AU2004252572B2 (en) 2003-06-25 2011-09-08 Novozymes A/S Polypeptides having alpha-amylase activity and polypeptides encoding same
EP2377931B1 (en) 2003-08-25 2013-05-08 Novozymes Inc. Variants of glycoside hydrolases
CN102994486A (zh) 2003-10-23 2013-03-27 诺维信公司 在洗涤剂中具有改善稳定性的蛋白酶
ES2437198T3 (es) 2003-10-28 2014-01-09 Novozymes Inc. Polipéptidos con actividad de beta-glucosidasa y polinucleótidos aislados que codifican los polipéptidos
ES2340390T3 (es) 2003-10-28 2010-06-02 Novozymes North America, Inc. Enzimas hibridas.
WO2005066339A2 (en) 2004-01-06 2005-07-21 Novozymes A/S Polypeptides of alicyclobacillus sp.
CN1980953B (zh) 2004-01-30 2014-12-24 诺维信股份有限公司 具有分解纤维增强活性的多肽及其编码多核苷酸
DK2322630T3 (en) 2004-02-12 2017-02-13 Novozymes Inc Polypeptides with xylanase activity and polynucleotides encoding them
NZ549198A (en) 2004-02-25 2009-05-31 Novozymes As Fungal cell wall degrading lysozyme for use as an inhibitor of dental biofilms
DK3219806T3 (da) 2004-03-25 2020-07-13 Novozymes Inc Fremgangsmåder til nedbrydning eller omdannelse af plantecellevægspolysaccharider
CN102286483B (zh) 2004-04-16 2014-06-04 中化帝斯曼制药有限公司荷兰公司 用于在真菌细胞中表达基因的真菌启动子
US7148404B2 (en) 2004-05-04 2006-12-12 Novozymes A/S Antimicrobial polypeptides
DK1766040T3 (da) 2004-05-27 2017-11-13 Novozymes Inc Fremgangsmåder til transformering og ekspressions-screening af filamentøse svampeceller med et DNA-bibliotek
US7413887B2 (en) 2004-05-27 2008-08-19 Genecor International, Inc. Trichoderma reesei glucoamylase and homologs thereof
EP1749092A2 (en) 2004-05-27 2007-02-07 Genencor International, Inc. Acid-stable alpha amylases having granular starch hydrolyzing activity and enzyme compositions
WO2005121333A1 (en) 2004-06-14 2005-12-22 Novozymes A/S Signal peptide for producing a polypeptide
WO2005123915A1 (en) 2004-06-21 2005-12-29 Novozymes A/S Stably maintained multiple copies of at least two orf in the same orientation
JP5623691B2 (ja) 2004-06-21 2014-11-12 ノボザイムスアクティーゼルスカブ プロテアーゼ
EP1769070A4 (en) 2004-06-29 2007-12-12 Novozymes Inc POLYPEPTIDES WITH ALPHA-GLUCOSIDASE ACTIVITY AND POLYNUCLEOTIDES THAT CODE
EP2302042A3 (en) 2004-09-30 2011-08-10 Novozymes A/S Polypeptides having lipase activity and polynucleotides encoding same
EP1809747B1 (en) 2004-10-04 2016-12-14 Novozymes A/S Polypeptides having phytase activity and polynucleotides encoding same
AR050895A1 (es) 2004-10-04 2006-11-29 Novozymes As Polipeptidos que tienen actividad de fitasa y polinucleotidos que los codifican
EP1814996A2 (en) 2004-11-19 2007-08-08 Novozymes A/S Polypeptides having antimicrobial activity and polynucleotides encoding same
EP2365068B1 (en) 2004-12-22 2017-03-01 Novozymes A/S Enzymes for starch processing
CA2595056A1 (en) 2005-01-24 2006-07-27 Dsm Ip Assets B.V. Method for producing a compound of interest in a filamentous fungal cell
WO2006097464A1 (en) 2005-03-16 2006-09-21 Novozymes A/S Recombinant expression of defensins in filamentous fungi
ATE473999T1 (de) 2005-03-22 2010-07-15 Novozymes As Polypeptide und nukleinsäuren, die diese codieren
AR053066A1 (es) 2005-04-26 2007-04-18 Novozymes As Arabinofuranosidasas
BRPI0610031A2 (pt) 2005-04-27 2010-05-18 Novozymes Inc polipeptìdeo isolado, polinucleotìdeo isolado, construção de ácido nucleico, célula hospedeira recombinante, métodos para produzir o polipeptìdeo e para produzir um mutante de uma célula precursora, célula mutante, métodos para produzir uma proteìna, e para produzir um polinucleotìdeo, polinucleotìdeo, mutante, composição detergente, e, método para degradar biomassa contendo celulose e hemi-celulose
US8119387B2 (en) 2005-08-16 2012-02-21 Novozymes A/S Polypeptides of strain Bacillus sp. P203
EP1922333B1 (en) 2005-08-26 2010-03-31 Novozymes Adenium Biotech A/S Polypeptides having antimicrobial activity and polynucleotides encoding same
EP1941023B1 (en) 2005-09-30 2017-04-05 Novozymes Inc. Methods for enhancing the degradation or conversion of cellulosic material
ATE514770T1 (de) 2005-10-17 2011-07-15 Novozymes As Verwendung von pilzmutanten zur expression von antikörpern
US20090176219A1 (en) 2005-11-29 2009-07-09 Lucie Parenicova Dna binding site of a transcriptional activator useful in gene expression
CN103740674A (zh) 2006-03-20 2014-04-23 诺维信股份有限公司 具有内切葡聚糖酶活性的多肽和编码该多肽的多核苷酸
EP2004817A2 (en) 2006-03-30 2008-12-24 Novozymes, Inc. Polypeptides having endoglucanase activity and polynucleotides encoding same
WO2007112739A1 (en) 2006-04-04 2007-10-11 Novozymes A/S Phytase variants
US8198046B2 (en) 2006-07-11 2012-06-12 Danisco Us Inc. KEX2 cleavage regions of recombinant fusion proteins
US20080026376A1 (en) 2006-07-11 2008-01-31 Huaming Wang KEX2 cleavage regions of recombinant fusion proteins
EP2044203B1 (en) 2006-07-14 2013-10-09 Novozymes, Inc. Methods for increasing expression of genes in a fungal cell
CN103451164A (zh) 2006-07-14 2013-12-18 诺维信股份有限公司 用于产生具有生物学活性的分泌型多肽的方法
ES2538360T3 (es) 2006-07-21 2015-06-19 Novozymes, Inc. Métodos para aumentar la secreción de polipéptidos que tienen actividad biológica
US8138321B2 (en) 2006-09-22 2012-03-20 Danisco Us Inc. Acetolactate synthase (ALS) selectable marker from Trichoderma reesei
MX2009003472A (es) 2006-10-10 2009-06-02 Danisco Us Inc Genencor Div Variantes de glucoamilasa con propiedades alteradas.
EP2431470B1 (en) 2006-11-30 2017-11-29 Novozymes A/S Dnase expression in recombinant host cells
US8680252B2 (en) 2006-12-10 2014-03-25 Dyadic International (Usa), Inc. Expression and high-throughput screening of complex expressed DNA libraries in filamentous fungi
US9862956B2 (en) 2006-12-10 2018-01-09 Danisco Us Inc. Expression and high-throughput screening of complex expressed DNA libraries in filamentous fungi
US8105812B2 (en) 2006-12-18 2012-01-31 Danisco Us Inc. Laccases, compositions and methods of use
US8143046B2 (en) 2007-02-07 2012-03-27 Danisco Us Inc., Genencor Division Variant Buttiauxella sp. phytases having altered properties
US20080220498A1 (en) 2007-03-06 2008-09-11 Cervin Marguerite A Variant Buttiauxella sp. phytases having altered properties
AU2008214663B2 (en) 2007-02-15 2013-10-03 Dsm Ip Assets B.V. A recombinant host cell for the production of a compound of interest
JP5643083B2 (ja) 2007-03-26 2014-12-17 ノボザイムス アクティーゼルスカブ ハフニア・フィターゼ
DE102007016139A1 (de) 2007-03-30 2008-10-02 Jenabios Gmbh Verfahren zur regioselektiven Oxygenierung von N-Heterozyklen
US20100221783A1 (en) 2007-05-09 2010-09-02 Novozymes A/S Expression Cloning Method Suitable for Selecting Library Clones Producing a Polypeptide of Interest
WO2008150376A1 (en) 2007-05-21 2008-12-11 Danisco Us, Inc., Genencor Division Use of an aspartic protease (nsp24) signal sequence for heterologous protein expression
CN101784669B (zh) 2007-08-24 2015-02-18 科德克希思公司 用于(r)-3-羟基四氢噻吩的立体选择性制备的改善的酮还原酶多肽
WO2009033071A2 (en) * 2007-09-07 2009-03-12 Dyadic International, Inc. Novel fungal enzymes
WO2009035500A1 (en) 2007-09-12 2009-03-19 Danisco Us Inc., Genencor Division Trichoderma promoter
WO2009037253A2 (en) 2007-09-18 2009-03-26 Novozymes A/S Polypeptides having tyrosinase activity and polynucleotides encoding same
US8592194B2 (en) 2007-10-09 2013-11-26 Danisco Us Inc. Glucoamylase variants with altered properties
BRPI0817853B1 (pt) 2007-10-09 2022-05-10 Danisco Us Inc Variantes de glucoamilase com propriedades alteradas, método de produção das mesmas, composição de enzima e microorganismo transgênico
EP2222842B1 (en) 2007-11-20 2014-10-15 Danisco US Inc. Glucoamylase variants with altered properties
BRPI0820552A2 (pt) 2007-11-27 2014-10-14 Novozymes As Polipetídeo isolado, polinucleotídeo isolado, construção de ácido nucléico, vetor de expressão recombinante, célula hospedeira recombinante, métodos para produzir o polipeptídeo, para produzir uma proteína, e para degradar ou converter um material de biomassa, planta, parte vegetal ou célula vegetal transgêncica, método, composição, e. uso do polipeptídio.
ES2490608T3 (es) 2007-12-06 2014-09-04 Novozymes A/S Polipéptidos con actividad de esterasa de acetilxilano y polinucleótidos que codifican los mismos
CA2709490A1 (en) 2007-12-19 2009-07-09 Novozymes A/S Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
DK2283124T3 (en) 2008-04-18 2016-09-05 Danisco Us Inc BUTTIAUXELLA SP. PHYTASE VARIANTS
US8709777B2 (en) 2008-06-06 2014-04-29 Novozymes A/S Variants of a family 44 xyloglucanase
WO2010008828A2 (en) 2008-06-24 2010-01-21 Codexis, Inc. Biocatalytic processes for the preparation of substantially stereomerically pure fused bicyclic proline compounds
EP2329013B1 (en) 2008-08-27 2015-10-28 Codexis, Inc. Ketoreductase polypeptides for the production of a 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine
US8206962B2 (en) 2008-09-26 2012-06-26 Novozymes A/S Hafnia phytase variants
ES2526867T3 (es) 2008-11-20 2015-01-16 Novozymes Inc. Polipéptido que tiene actividad potenciadora amilolítica y polinucleótidos que codifican el mismo
CA2745760A1 (en) 2008-12-04 2010-06-10 Novozymes A/S Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
US9493759B2 (en) 2008-12-12 2016-11-15 Novozymes, Inc. Polypeptides having aspartic endopeptidase activity and polynucleotides encoding same
US20110296557A1 (en) 2008-12-12 2011-12-01 Novozymes, Inc. Polypeptides Having Lipase Activity And Polynucleotides Encoding Same
US20110269206A1 (en) 2008-12-15 2011-11-03 Novozymes, Inc Polypeptides Having Catalase Activity And Polynucleotides Encoding Same
EP2379716A1 (en) 2008-12-16 2011-10-26 Novozymes Inc. Polypeptides having alpha-mannosidase activity and polynucleotides encoding same
US8633030B2 (en) 2008-12-16 2014-01-21 Novozymes, Inc. Polypeptides having carboxypeptidase activity and polynucleotides encoding same
WO2010080527A1 (en) 2008-12-19 2010-07-15 Novozymes, Inc. Methods for determining cellulolytic enhancing activity of a polypeptide
DK2379712T3 (en) 2008-12-19 2017-05-08 Novozymes Inc Methods for Increasing Hydrolysis of Cellulosic Material in the Presence of Cellobiose Dehydrogenase
WO2010080407A2 (en) 2008-12-19 2010-07-15 Novozymes, Inc. Methods for increasing hydrolysis of cellulosic material
CN102325893A (zh) 2008-12-19 2012-01-18 诺维信股份有限公司 在过氧化物酶存在下增加纤维素材料酶法水解的方法
EP2382309B1 (en) 2008-12-23 2015-12-23 DuPont Nutrition Biosciences ApS Polypeptides with xylanase activity
US8349325B2 (en) 2008-12-23 2013-01-08 Abbott Laboratories Soluble FMS-like tyrosine kinase-1 (sFLT-1) antibody and related composition, kit, methods of using, and materials and method for making
CN102341494B (zh) 2009-01-08 2014-10-15 科德克希思公司 转氨酶多肽
EP2389437B1 (en) 2009-01-21 2015-10-21 Novozymes A/S Polypeptides having esterase activity and nucleic acids encoding the same
US8604277B2 (en) 2009-01-28 2013-12-10 Novozymes, Inc. Polypeptides having beta-glucosidase activity and polynucleotides encoding same
WO2010088463A2 (en) 2009-01-30 2010-08-05 Novozymes, Inc. Polypeptides having expansin activity and polynucleotides encoding same
WO2010088447A1 (en) 2009-01-30 2010-08-05 Novozymes A/S Polypeptides having alpha-amylase activity and polynucleotides encoding same
WO2010091221A1 (en) 2009-02-06 2010-08-12 Novozymes A/S Polypeptides having alpha-amylase activity and polynucleotides encoding same
US8563268B2 (en) 2009-03-17 2013-10-22 Novozymes A/S Polypeptide having tyrosinase activity
US8658409B2 (en) 2009-03-24 2014-02-25 Novozymes A/S Polypeptides having acetyl xylan esterase activity and polynucleotides encoding same
WO2010120557A1 (en) 2009-03-31 2010-10-21 Codexis, Inc. Improved endoglucanases
CA2758404A1 (en) 2009-04-22 2010-10-28 Dsm Ip Assets B.V. Process for the production of a recombinant polypeptide of interest
EP2248893A1 (en) 2009-05-06 2010-11-10 Novozymes A/S DFPase Enzymes from Octopus Vulgaris
EP2432890B1 (en) 2009-05-22 2015-09-02 Codexis, Inc. Engineered biosynthesis of fatty alcohols
AU2010253848C1 (en) 2009-05-29 2015-02-19 Novozymes, Inc. Methods for enhancing the degradation or conversion of cellulosic material
ES2534078T3 (es) 2009-06-02 2015-04-17 Novozymes Inc. Polipéptidos con actividad de celobiohidrolasa y polinucleótidos que codifican los mismos
WO2011005527A2 (en) 2009-06-22 2011-01-13 Codexis, Inc. Ketoreductase-mediated stereoselective route to alpha chloroalcohols
WO2010151787A1 (en) 2009-06-26 2010-12-29 Novozymes North America, Inc. Heat-stable carbonic anhydrases and their use
WO2011008535A1 (en) 2009-06-30 2011-01-20 Codexis, Inc. Production of fatty alcohols with fatty alcohol forming acyl-coa reductases (far)
CA2767169A1 (en) 2009-07-07 2011-01-13 Novozymes, Inc. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
WO2011009700A1 (en) 2009-07-22 2011-01-27 Dsm Ip Assets B.V. Improved host cell for the production of a compound of interest
WO2011009747A1 (en) 2009-07-24 2011-01-27 Novozymes A/S Carbohydrate oxidases
WO2011014458A1 (en) 2009-07-28 2011-02-03 Novozymes, Inc. Polypeptides having phytase activity and polynucleotides encoding same
EP2462156A1 (en) 2009-08-07 2012-06-13 Novozymes A/S Method of producing a sweet protein
EP2467475A1 (en) 2009-08-19 2012-06-27 Danisco US Inc. Combinatorial variants of glucoamylase with improved specific activity and/or thermostability
EP2467474A1 (en) 2009-08-19 2012-06-27 Danisco A/S Variants of glucoamylase
WO2011020910A1 (en) 2009-08-21 2011-02-24 Novozymes A/S Polypeptides having isoamylase activity and polynucleotides encoding same
WO2011028643A1 (en) 2009-09-01 2011-03-10 Novozymes, Inc. Methods for improving malic acid production in filamentous fungi
WO2011035027A2 (en) 2009-09-17 2011-03-24 Novozymes, Inc. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
CN102712916B (zh) 2009-09-18 2015-11-25 诺维信股份有限公司 具有β-葡糖苷酶活性的多肽和编码该多肽的多核苷酸
JP5947213B2 (ja) 2009-09-25 2016-07-06 ノボザイムス アクティーゼルスカブ プロテアーゼ変異体の使用
RU2639534C2 (ru) 2009-09-25 2017-12-21 Новозимс А/С Применение вариантов протеазы
CN102648276A (zh) 2009-09-29 2012-08-22 诺维信股份有限公司 具有木聚糖酶活性的多肽和编码该多肽的多核苷酸
ES2560805T3 (es) 2009-09-29 2016-02-22 Novozymes Inc. Polipéptidos con actividad mejoradora celulolítica y polinucleótidos que los codifican
EP2977382A3 (en) 2009-09-30 2016-05-11 Novozymes Inc. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
CN102666846A (zh) 2009-09-30 2012-09-12 诺维信公司 具有纤维素分解增强活性的多肽和编码该多肽的多核苷酸
ES2538396T3 (es) 2009-09-30 2015-06-19 Codexis, Inc. C1 ß-glucosidasa recombinante para la producción de azúcares a partir de biomasa celulósica
WO2011050037A1 (en) 2009-10-23 2011-04-28 Novozymes, Inc. Cellobiohydrolase variants and polynucleotides encoding same
US20120260371A1 (en) 2009-10-29 2012-10-11 Novozymes A/S Polypeptides Having Cellobiohydrolase Activity and Polynucleotides Encoding Same
CN102639697B (zh) 2009-11-06 2015-03-25 诺维信股份有限公司 具有木聚糖酶活性的多肽和编码该多肽的多核苷酸
EP2496693B1 (en) 2009-11-06 2017-10-25 Novozymes, Inc. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same
DK2496694T3 (en) 2009-11-06 2017-06-06 Novozymes Inc COMPOSITIONS FOR SACCHARIFYING CELLULOS MATERIAL
CN102666848B (zh) 2009-11-25 2014-09-24 科德克希思公司 用于从纤维素生物质产生可发酵的糖的重组嗜热子囊菌β-葡糖苷酶变体
EP2504017B1 (en) 2009-11-25 2014-01-08 Codexis, Inc. Recombinant beta-glucosidase variants for production of soluble sugars from cellulosic biomass
CA2782154C (en) 2009-11-30 2018-10-16 Novozymes A/S Polypeptides having glucoamylase activity and polynucleotides encoding same
ES2534066T3 (es) 2009-11-30 2015-04-17 Novozymes A/S Polipéptidos que tienen actividad de glucoamilasa y polinucleótidos que codifican los mismos
CA2782036C (en) 2009-12-01 2019-01-15 Novozymes A/S Polypeptides having glucoamylase activity and polynucleotides encoding same
EP2507369A1 (en) 2009-12-03 2012-10-10 Novozymes A/S Variants of a polypeptide with lipolytic activity and improved stability
EP2509427B1 (en) 2009-12-09 2017-08-02 Novozymes A/S Methods of producing gh8 xylanase variants
DK2510093T3 (en) 2009-12-11 2018-06-06 Novozymes North America Inc protease Variants
BR112012013205B1 (pt) 2009-12-18 2020-11-03 Novozymes, Inc. mutante de uma cepa parental de trichoderma reesei, e, métodos para produzir um polipeptídeo de interesse e para obter um mutante de uma cepa parental de trichoderma
EP2501792A2 (en) 2009-12-29 2012-09-26 Novozymes A/S Gh61 polypeptides having detergency enhancing effect
CN102884183B (zh) 2010-01-04 2015-09-16 诺维信公司 趋于钙耗竭和酸性pH的α-淀粉酶的稳定化
US8617856B2 (en) 2010-01-07 2013-12-31 Wisconsin Alumni Research Foundation Fatty acid-producing hosts
EA201201125A1 (ru) 2010-02-11 2013-03-29 ДСМ АйПи АССЕТС Б.В. Клетка-хозяин, способная продуцировать ферменты, пригодные для деградации лигноцеллюлозного материала
US8865637B2 (en) 2010-02-25 2014-10-21 Novozymes Als Variants of a lysozyme and polynucleotides encoding same
WO2011104284A1 (en) 2010-02-25 2011-09-01 Novozymes A/S Polypeptides having antimicrobial activity
CA2791353A1 (en) 2010-03-03 2011-09-09 Novozymes, Inc. Xylanase variants and polynucleotides encoding same
US20110229921A1 (en) 2010-03-18 2011-09-22 Abbott Laboratories METHODS OF ASSAYING URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (uNGAL) IN THE PROGNOSIS OF CADAVERIC KIDNEY TRANSPLANT FUNCTION IN A PATIENT, INCLUDING A PATIENT DIAGNOSED WITH DELAYED GRAFT FUNCTION (DGF), A METHOD OF ASSAYING uNGAL IN THE ASSESSMENT OF RISK OF DGF IN A PATIENT DIAGNOSED WITH EARLY GRAFT FUNCTION (EGF), AND RELATED KITS
CN102917600B (zh) 2010-03-26 2015-07-08 诺维信公司 热稳定性肌醇六磷酸酶变体
US8828701B2 (en) 2010-03-31 2014-09-09 Novozymes, Inc. Cellobiohydrolase variants and polynucleotides encoding same
MX338068B (es) 2010-04-14 2016-04-01 Novozymes As Polipeptidos que tienen actividad de glucoamilasa y polinucleotidos que codifican los mismos.
CA2798937A1 (en) 2010-05-28 2011-12-01 Codexis, Inc. Pentose fermentation by a recombinant microorganism
DK2576606T3 (en) 2010-06-04 2015-02-23 Novozymes Inc Preparation of C4 dicarboxylic acid in filamentous fungi
US8835604B2 (en) 2010-06-12 2014-09-16 Adenium Biotech Aos Antimicrobial peptide variants and polynucleotides encoding same
DK2769985T3 (da) 2010-06-21 2018-01-29 Novozymes Inc Polypeptider fra Aspergillus aculeatus med C4-dicarboxylsyre-transportøraktivitet samt polynukleotider, som koder for samme
IN2013CN00459A (zh) 2010-06-21 2015-07-03 Novozymes Inc
US8802412B2 (en) 2010-06-25 2014-08-12 Novozymes A/S Polynucleotides having promoter activity
US9551714B2 (en) 2010-06-25 2017-01-24 Abbott Laboratories Materials and methods for assay of anti-hepatitis C virus (HCV) antibodies
CN103068978B (zh) 2010-06-25 2017-01-18 诺维信公司 具有前导序列功能的多核苷酸
CN103068988A (zh) 2010-06-25 2013-04-24 诺维信公司 具有启动子活性的多核苷酸
EP2585587B1 (en) 2010-06-28 2017-08-09 Codexis, Inc. Fatty alcohol forming acyl reductases (fars) and methods of use thereof
DK2588604T3 (en) 2010-06-30 2016-09-26 Novozymes Inc Polypeptides having beta-glucosidase activity and polynucleotides encoding them
CA2803222A1 (en) 2010-07-01 2012-01-05 Dsm Ip Assets B.V. A method for the production of a compound of interest
US8865448B2 (en) 2010-07-30 2014-10-21 Cleanvantage Llc Aspergillus containing beta-glucosidase, beta-glucosidases and nucleic acids encoding the same
US9057086B2 (en) 2010-08-12 2015-06-16 Novozymes, Inc. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicycle compound and uses thereof
CN103298921A (zh) 2010-08-17 2013-09-11 诺维信公司 酿造方法
CN103080306B (zh) 2010-08-20 2015-02-18 科德克希思公司 糖苷水解酶61家族蛋白在纤维素加工中的用途
WO2012025577A1 (en) 2010-08-24 2012-03-01 Novozymes A/S Heat-stable persephonella carbonic anhydrases and their use
WO2012030811A1 (en) 2010-08-30 2012-03-08 Novozymes A/S Polypeptides having cellobiohydrolase activity and polynucleotides encoding same
EP2611914A1 (en) 2010-08-30 2013-07-10 Novozymes A/S Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
US20130212746A1 (en) 2010-08-30 2013-08-15 Novoyzmes A/S Polypeptides Having Hemicellulolytic Activity And Polynucleotides Encoding Same
EP2611901B1 (en) 2010-08-30 2016-05-11 Novozymes A/S Polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same
WO2012030849A1 (en) 2010-08-30 2012-03-08 Novozymes A/S Polypeptides having xylanase activity and polynucleotides encoding same
US9267126B2 (en) 2010-08-30 2016-02-23 Novozymes, Inc. Polypeptides having endoglucanase activity and polynucleotides encoding same
US20130266554A1 (en) 2010-09-16 2013-10-10 Novozymes A/S Lysozymes
ES2599613T3 (es) 2010-09-30 2017-02-02 Novozymes, Inc. Variantes de polipéptidos que tienen actividad de mejora celulolítica y polinucleótidos que codifican los mismos
CN103282489B (zh) 2010-09-30 2016-12-14 诺维信股份有限公司 具有纤维素分解增强活性的多肽变体及其编码多核苷酸
CA2809916A1 (en) 2010-10-01 2012-04-05 Novozymes A/S Polypeptides having endopeptidase activity and polynucleotides encoding same
MX2013002586A (es) 2010-10-01 2013-03-21 Novozymes Inc Variantes de beta-glucosidasa y polinucleotidos que codifican las mismas.
BR112013009817B1 (pt) 2010-10-26 2020-02-04 Novozymes As métodos de degradar ou converter refugo de cana de açúcar, de produzir um produto de fermentação, e, de fermentar refugo de cana de açúcar
US8728804B2 (en) 2010-10-29 2014-05-20 Novozymes A/S Polypeptides having succinyl-CoA: acetoacetate transferase activity and polynucleotides encoding same
US20130280775A1 (en) 2010-10-29 2013-10-24 Novozymes, Inc. Recombinant N-propanol and Isopropanol Production
BR112013010008B1 (pt) 2010-11-02 2020-09-08 Novozymes, Inc. Métodos para degradar e para fermentar um material celulósico, e para produzir um produto de fermentação
US9212354B2 (en) 2010-11-04 2015-12-15 Novozymes Inc. Polypeptides having cellobiohydrolase activitiy and polynucleotides encoding same
US9309505B2 (en) 2010-11-08 2016-04-12 Novozymes North America, Inc. Polypeptides having glucoamylase activity and polynucleotides encoding same
EP2638154B1 (en) 2010-11-08 2016-09-14 Novozymes A/S Polypeptides having glucoamylase activity and polynucleotides encoding same
US20120115244A1 (en) 2010-11-09 2012-05-10 Abbott Laboratories Materials and methods for immunoassay of pterins
US9139823B2 (en) 2010-11-12 2015-09-22 Novozymes, Inc. Polypeptides having endoglucanase activity and polynucleotides encoding same
MX356647B (es) 2010-11-12 2018-06-07 Novozymes As Polipeptidos que tienen actividad de fosfolipasa c y polinucleotidos que codifican los mismos.
WO2012068509A1 (en) 2010-11-18 2012-05-24 Novozymes, Inc. Chimeric polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
EP2646558B1 (en) 2010-11-30 2016-07-20 Novozymes, Inc. Promoters for expressing genes in a fungal cell
EP2649188A1 (en) 2010-12-06 2013-10-16 Novozymes North America, Inc. Methods of hydrolyzing oligomers in hemicellulosic liquor
WO2012078712A2 (en) 2010-12-07 2012-06-14 Vnomics Corp. System and method for measuring and reducing vehicle fuel waste
US9284588B2 (en) 2010-12-16 2016-03-15 Novozymes, Inc. Promoters for expressing genes in a fungal cell
CN103443268A (zh) 2011-01-20 2013-12-11 诺维信公司 植物过氧化物酶在丝状真菌中的表达
WO2012103293A1 (en) 2011-01-26 2012-08-02 Novozymes A/S Polypeptides having cellobiohydrolase activity and polynucleotides encoding same
MX337942B (es) 2011-01-26 2016-03-29 Novozymes As Polipeptidos que tienen actividad de endoglucanasa y polinucleotidos que codifican los mismos.
MX2013007720A (es) 2011-01-26 2013-08-09 Novozymes As Polipeptidos que tienen actividad celobiohidrolasa y polinucleotidos que codifican para los mismos.
WO2012103288A1 (en) 2011-01-26 2012-08-02 Novozymes A/S Polypeptides having cellobiohydrolase activity and polynucleotides encoding same
US9506048B2 (en) 2011-01-26 2016-11-29 Novozymes, Inc. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same
DK2670853T3 (en) 2011-01-31 2017-08-28 Novozymes North America Inc Process for enzymatic refining of pretreated cellulosic material for sugars
EP2678427A2 (en) 2011-02-23 2014-01-01 DuPont Nutrition Biosciences ApS Method for producing recombinant enzymes capable of hydrolysing chlorophyll or a chlorophyll derivative
EP2678352B1 (en) 2011-02-23 2017-12-06 Novozymes, Inc. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
BR112013019036A2 (pt) 2011-02-28 2017-04-04 Novozymes Inc célula hospedeira recombinante, e, método para produzir um ácido dicarboxílico.
CN103608461B (zh) 2011-03-09 2016-08-03 诺维信公司 增加多肽的纤维素分解增强活性的方法
US9409958B2 (en) 2011-03-10 2016-08-09 Novozymes, Inc. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
CN103596970A (zh) 2011-03-11 2014-02-19 帝斯曼知识产权资产管理有限公司 载体-宿主系统
DK2689011T3 (en) 2011-03-25 2018-01-22 Novozymes As PROCEDURE FOR DEGRADATION OR CONVERSION OF CELLULOSE-SUBSTANCING MATERIAL
WO2012135110A1 (en) 2011-03-30 2012-10-04 Codexis, Inc. Pentose fermentation by a recombinant microorganism
WO2012135659A2 (en) 2011-03-31 2012-10-04 Novozymes A/S Methods for enhancing the degradation or conversion of cellulosic material
WO2012135719A1 (en) 2011-03-31 2012-10-04 Novozymes, Inc. Cellulose binding domain variants and polynucleotides encoding same
US9926547B2 (en) 2011-04-28 2018-03-27 Novozymes, Inc. Polypeptides having endoglucanase activity and polynucleotides encoding same
BR112013027463A2 (pt) 2011-04-29 2017-09-26 Novozymes Inc métodos para degradar ou converter, e para fermentar um material celulóliso, para produzir um produto de fermentação, e para limpar ou lavar uma superfície dura ou roupa suja, e, composição de detergente
US20140141471A1 (en) 2011-05-19 2014-05-22 Novozymes, Inc. Methods for Enhancing the Degradation of Cellulosic Material with Chitin Binding Proteins
WO2012159009A1 (en) 2011-05-19 2012-11-22 Novozymes, Inc. Methods for enhancing the degradation of cellulosic material with chitin binding proteins
EP2527448A1 (en) 2011-05-23 2012-11-28 Novozymes A/S Simultaneous site-specific integrations of multiple gene-copies in filamentous fungi
EP2527432A1 (en) 2011-05-23 2012-11-28 Novozymes A/S Bi-directional cytosine deaminase-encoding selection marker
CN103620029B (zh) 2011-06-24 2017-06-09 诺维信公司 具有蛋白酶活性的多肽和编码它们的多核苷酸
EP2726651B1 (en) 2011-06-28 2018-11-07 Codexis, Inc. Protein variant generation by region shuffling
US20140206026A1 (en) 2011-06-30 2014-07-24 Novozymes A/S Method for Screening Alpha-Amylases
JP6204352B2 (ja) 2011-06-30 2017-09-27 ノボザイムス アクティーゼルスカブ α−アミラーゼ変異体
US8778652B2 (en) 2011-06-30 2014-07-15 Codexis, Inc. Pentose fermentation by a recombinant microorganism
EA201490216A1 (ru) 2011-07-06 2014-07-30 Новозимс А/С Варианты альфа-амилазы и кодирующие их полинуклеотиды
EP2732033A1 (en) 2011-07-15 2014-05-21 Novozymes A/S Lipase variants and polynucleotides encoding same
US20140147895A1 (en) 2011-07-22 2014-05-29 Novozymes A/S Processes for Pretreating Cellulosic Material and Improving Hydrolysis Thereof
BR112014002401B1 (pt) 2011-08-04 2021-08-03 Novozymes A/S Célula hospedeira transgênica de fungo filamentoso, métodos para produzir um polipeptídeo e uma proteína, e, construto de ácido nucleico ou um vetor de expressão
BR112014002405A2 (pt) 2011-08-04 2017-04-04 Novozymes As polopeptídeo e polinucleotídeo isolados, composição, construto de ácido nucleico ou vetor de expressão, célula hospedeira recombinante, planta transgênica, parte da planta ou célula de planta, métodos para produzir um polipeptídeo e uma proteína, e, processos para degradar um material celulóssico, para produzir um produto de fermentação, e para fermentar um material celulósico
US9506044B2 (en) 2011-08-10 2016-11-29 Novozymes A/S Polypeptides having peroxygenase activity and polynucleotides encoding same
WO2013021062A1 (en) 2011-08-10 2013-02-14 Novozymes A/S Polypeptides having peroxygenase activity and polynucleotides encoding same
CN103732740B (zh) 2011-08-10 2018-07-31 诺维信公司 具有过氧化酶活性的多肽及编码该多肽的多核苷酸
WO2013021065A1 (en) 2011-08-10 2013-02-14 Novozymes A/S Polypeptides having peroxygenase activity and polynucleotides encoding same
CN103827297B (zh) 2011-08-10 2018-06-22 诺维信公司 具有过氧化酶活性的多肽及编码该多肽的多核苷酸
WO2013021059A1 (en) 2011-08-10 2013-02-14 Novozymes A/S Polypeptides having peroxygenase activity and polynucleotides encoding same
WO2013021064A1 (en) 2011-08-10 2013-02-14 Novozymes A/S Polypeptides having peroxygenase activity and polynucleotides encoding same
WO2013024021A1 (en) 2011-08-15 2013-02-21 Novozymes A/S Polypeptides having cellulase activity and polynucleotides encoding same
US20140295027A1 (en) 2011-08-19 2014-10-02 Novozymes A/S Polypeptides Having Protease Activity
CN103917649A (zh) 2011-08-19 2014-07-09 诺维信股份有限公司 用于生产c4-二羧酸的重组微生物
EP2748317B1 (en) 2011-08-22 2017-04-19 Codexis, Inc. Gh61 glycoside hydrolase protein variants and cofactors that enhance gh61 activity
CN103890165A (zh) 2011-08-24 2014-06-25 诺维信股份有限公司 纤维素分解酶组合物及其用途
AU2012298713B2 (en) 2011-08-24 2017-11-23 Novozymes, Inc. Methods for obtaining positive transformants of a filamentous fungal host cell
EP2748314B1 (en) 2011-08-24 2016-12-28 Novozymes, Inc. Aspergillus fumigatus cellulolytic enzyme compositions and uses thereof
BR112014004190A2 (pt) 2011-08-24 2017-03-01 Novozymes Inc método para construir uma cepa fúngida filamentosa, cepa fúngida filamentosa, método para produzir múltiplos polipeptídeos recombinantes, e, construto em tandem
CA2846690A1 (en) 2011-08-26 2013-03-07 Novozymes A/S Polypeptides having glucoamylase activity and polynucleotides encoding same
IN2014CN02469A (zh) 2011-09-06 2015-06-19 Novozymes As
US9109209B2 (en) 2011-09-08 2015-08-18 Codexis, Inc. Biocatalysts and methods for the synthesis of substituted lactams
US9994834B2 (en) 2011-09-09 2018-06-12 Novozymes A/S Polynucleotides encoding polypeptides having alpha-amylase activity and methods of making the same
CN103930555A (zh) 2011-09-13 2014-07-16 诺维信北美公司 水解和发酵纤维素材料的方法
WO2013043910A1 (en) 2011-09-20 2013-03-28 Novozymes A/S Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
ES2628190T3 (es) 2011-09-22 2017-08-02 Novozymes A/S Polipéptidos con actividad de proteasa y polinucleótidos que codifican los mismos
US8728788B1 (en) 2011-09-30 2014-05-20 Novozymes A/S Dehydrogenase variants and polynucleotides encoding same
WO2013044867A1 (en) 2011-09-30 2013-04-04 Novozymes A/S Polypeptides having alpha-amylase activity and polynucleotides encoding same
CN103930438A (zh) 2011-09-30 2014-07-16 诺维信股份有限公司 具有β-葡糖苷酶活性的嵌合多肽和对其进行编码的多核苷酸
WO2013052604A1 (en) 2011-10-04 2013-04-11 University Of Florida Research Foundation, Inc. Variants of glycerol dehydrogenase having d-lactate dehydrogenase activity and uses thereof
MX351762B (es) 2011-10-11 2017-10-26 Novozymes As Variantes de glucoamilasas y polinucleotidos que las codifican.
CN103857794B (zh) 2011-10-17 2018-03-20 诺维信公司 α‑淀粉酶变体以及编码它们的多核苷酸
MX354704B (es) 2011-10-17 2018-03-16 Novozymes As Variantes de alfa-amilasa y polinucleotidos que codifican las mismas.
CA2851308A1 (en) 2011-10-31 2013-05-10 Bp Corporation North America Inc. Use of mammalian promoters in filamentous fungi
EP2773656B1 (en) 2011-10-31 2019-06-19 Novozymes, Inc. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
CA2851855A1 (en) 2011-10-31 2013-05-10 Bp Corporation North America Inc. Use of plant promoters in filamentous fungi
BR112014011902A2 (pt) 2011-11-18 2017-05-16 Novozymes As polipeptídeo e polinucleotídeo isolados, célula hospedeira recombinante, métodos para produzir um polipeptídeo, e para produzir um mutante de uma célula parental, processos para produzir uma proteína, para degradar ou converter um material celulósico ou material contendo xilano, para produzir um produto de fermentação, e para fermentar um material celulósico ou material contendo xilano, e, formulação de caldo integral ou composição de cultura de células
EP2802651B1 (en) 2011-11-21 2017-03-08 Novozymes, Inc. Gh61 polypeptide variants and polynucleotides encoding same
DK2782998T3 (en) 2011-11-22 2018-04-16 Novozymes Inc POLYPEPTIDES WITH BETA-XYLOSIDASE ACTIVITY AND POLYNUCLEOTIDES CODING THEM
CN107090445A (zh) 2011-11-25 2017-08-25 诺维信公司 具有溶菌酶活性的多肽和编码所述多肽的多核苷酸
EP2785732B1 (en) 2011-12-01 2017-04-12 Novozymes, Inc. Polypeptides having beta-xylosidase activity and polynucleotides encoding same
WO2013079533A1 (en) 2011-12-02 2013-06-06 Novozymes A/S Polypeptides having peroxygenase activity and polynucleotides encoding same
US9169469B2 (en) 2011-12-02 2015-10-27 Novozymes A/S Polypeptides having peroxygenase activity and polynucleotides encoding same
JP6378089B2 (ja) 2011-12-09 2018-08-22 ダニスコ・ユーエス・インク 微生物におけるタンパク質産生のための、Ｂ．ズブチリス（Ｂ．ｓｕｂｔｉｌｉｓ）からのリボソームプロモーター
EP3272862A1 (en) 2011-12-16 2018-01-24 Novozymes, Inc. Polypeptides having laccase activity and polynucleotides encoding same
EP2794870A4 (en) 2011-12-19 2015-06-17 Novozymes Inc POLYPEPTIDES WITH XYLANASE ACTIVITY AND POLYNUCLEOTIDES THAT CODE
WO2013096244A1 (en) 2011-12-20 2013-06-27 Codexis, Inc. Endoglucanase 1b (eg1b) variants
CA2878019A1 (en) 2011-12-20 2013-06-27 Novozymes, Inc. Cellobiohydrolase variants and polynucleotides encoding same
CN104024408B (zh) 2011-12-28 2019-04-19 诺维信公司 具有蛋白酶活性的多肽
US8993248B2 (en) 2011-12-31 2015-03-31 Abbott Laboratories Truncated human vitamin D binding protein and mutation and fusion thereof and related materials and methods of use
EP2807254B1 (en) 2012-01-26 2017-08-02 Novozymes A/S Use of polypeptides having protease activity in animal feed and detergents
MX353896B (es) 2012-02-03 2018-02-01 Procter & Gamble Composiciones y metodos para el tratamiento de superficies con lipasas.
ES2794644T3 (es) 2012-02-03 2020-11-18 Novozymes As Variantes de lipasa y polinucleótidos que las codifican
WO2013123871A1 (en) 2012-02-20 2013-08-29 Novozymes A/S Polypeptides having endoglucanase activity and polynucleotides encoding same
WO2013142770A1 (en) 2012-03-23 2013-09-26 Codexis, Inc. Biocatalysts and methods for synthesizing derivatives of tryptamine and tryptamine analogs
WO2013149858A1 (en) 2012-04-02 2013-10-10 Novozymes A/S Lipase variants and polynucleotides encoding same
CN104245929A (zh) 2012-04-23 2014-12-24 诺维信公司 具有α-葡糖醛酸糖苷酶活性的多肽以及编码其的多核苷酸
US9394556B2 (en) 2012-04-23 2016-07-19 Novozymes A/S Polypeptides having glucuronyl esterase activity and polynucleotides encoding same
CN113234695A (zh) 2012-04-27 2021-08-10 诺维信股份有限公司 Gh61多肽变体以及编码其的多核苷酸
AR090971A1 (es) 2012-05-07 2014-12-17 Novozymes As Polipeptidos que tienen actividad de degradacion de xantano y polinucleotidos que los codifican
SG11201407295YA (en) 2012-05-08 2014-12-30 Codexis Inc Biocatalysts and methods for hydroxylation of chemical compounds
WO2013170050A1 (en) 2012-05-11 2013-11-14 Codexis, Inc. Engineered imine reductases and methods for the reductive amination of ketone and amine compounds
WO2013178674A1 (en) 2012-05-31 2013-12-05 Novozymes A/S Improved selection in fungi
WO2013178808A2 (en) 2012-05-31 2013-12-05 Novozymes A/S Polypeptides having organophosphorous hydrolase activity
WO2013188305A2 (en) 2012-06-11 2013-12-19 Codexis, Inc. Fungal beta-xylosidase variants
WO2013189878A1 (en) 2012-06-19 2013-12-27 Dsm Ip Assets B.V. Promoters for expressing a gene in a cell
MX364390B (es) 2012-06-20 2019-04-25 Novozymes As Uso de polipeptidos que tienen actividad proteasa en alimentos para animales y detergentes.
CN104471048B (zh) 2012-07-12 2018-11-16 诺维信公司 具有脂肪酶活性的多肽及编码它的多核苷酸
DK2875119T3 (en) 2012-07-19 2018-04-03 Dsm Ip Assets Bv AGSE-DEFICIENT TRIALS
DK2885407T3 (en) 2012-08-16 2018-07-16 Bangladesh Jute Res Institute DESTROYING ENZYMES FROM MACROPHOMINA PHASEOLINA AND ITS APPLICATIONS
JP6616687B2 (ja) 2012-08-16 2019-12-04 バングラデシュ ジュート リサーチ インスティテュート Ｍａｃｒｏｐｈｏｍｉｎａｐｈａｓｅｏｌｉｎａ由来のセルロースおよび／またはヘミセルロース分解酵素およびその使用
CN104540394A (zh) 2012-08-17 2015-04-22 诺维信公司 热稳定天冬酰胺酶变体以及对其进行编码的多核苷酸
EP2885409A1 (en) 2012-08-17 2015-06-24 Novozymes A/S Methods for co-silencing expression of genes in filamentous fungal strains and uses thereof
MX2015002211A (es) 2012-08-22 2015-05-08 Novozymes As Metaloproteasa de exiguobacterium.
MX2015002099A (es) 2012-08-22 2015-05-11 Dupont Nutrition Biosci Aps Variantes que tienen actividad glucoamilasa.
EP2888360B1 (en) 2012-08-22 2017-10-25 Novozymes A/S Metalloproteases from alicyclobacillus sp.
CN104884615B (zh) 2012-09-05 2019-07-12 诺维信公司 具有蛋白酶活性的多肽
US20140073022A1 (en) 2012-09-10 2014-03-13 Wisconsin Alumni Research Foundation Production of polyhydroxyalkanoates with a defined composition from an unrelated carbon source
EP2898076B1 (en) 2012-09-19 2018-03-07 DSM IP Assets B.V. Cell modification method using essential genes as markers and optionally recycling these
BR112015005884A2 (pt) 2012-09-19 2017-08-08 Novozymes Inc E Novozymes As processos para degradação de um material celulósico, para produção de um produto da fermentação, e de fermentação de um material celulósico, composição, e, formulação de caldo inteiro ou composição de cultura de células
EP2903412B1 (en) 2012-10-08 2019-09-11 Novozymes A/S Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
WO2014056917A2 (en) 2012-10-12 2014-04-17 Novozymes A/S Polypeptides having peroxygenase activity
EP2906688B1 (en) 2012-10-12 2018-08-29 Novozymes A/S Polypeptides having peroxygenase activity
WO2014056916A2 (en) 2012-10-12 2014-04-17 Novozymes A/S Polypeptides having peroxygenase activity
WO2014056920A2 (en) 2012-10-12 2014-04-17 Novozymes A/S Polypeptides having peroxygenase activity
US9499801B2 (en) 2012-10-12 2016-11-22 Novozymes A/S Polypeptides having peroxygenase activity
CN104718286B (zh) 2012-10-12 2018-10-30 诺维信公司 具有过氧合酶活性的多肽
WO2014056919A2 (en) 2012-10-12 2014-04-17 Novozymes A/S Polypeptides having peroxygenase activity
US20150275194A1 (en) 2012-10-24 2015-10-01 Novozymes A/S Polypeptides Having Cellulolytic Enhancing Activity And Polynucleotides Encoding Same
WO2014076232A2 (en) 2012-11-19 2014-05-22 Novozymes A/S Isopropanol production by recombinant hosts using an hmg-coa intermediate
US9611515B2 (en) 2012-11-20 2017-04-04 Codexis, Inc. Pentose fermentation by a recombinant microorganism
EP2925774B8 (en) 2012-11-29 2018-03-07 The Texas A&M University System Engineering the production of a conformational variant of occidiofungin that has enhanced inhibitory activity against fungal species
WO2014086706A1 (en) 2012-12-07 2014-06-12 Novozymes A/S Method for generating site-specific mutations in filamentous fungi
EP2931744B1 (en) 2012-12-11 2021-08-18 Novozymes A/S Polypeptides having phospholipase c activity and polynucleotides encoding same
WO2014093835A1 (en) 2012-12-14 2014-06-19 Novozymes A/S Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same
US9765317B2 (en) 2012-12-17 2017-09-19 Novozymes A/S Alpha-amylases and polynucleotides encoding same
WO2014099798A1 (en) 2012-12-19 2014-06-26 Novozymes A/S Polypeptides having cellulolytic enhancinc activity and polynucleotides encoding same
ES2655032T3 (es) 2012-12-21 2018-02-16 Novozymes A/S Polipéptidos que poseen actividad proteasa y polinucleótidos que los codifican
DK2935572T3 (da) 2012-12-21 2020-11-16 Codexis Inc Modificerede biokatalysatorer og fremgangsmåder til syntetisering af chirale aminer
WO2014100612A1 (en) 2012-12-21 2014-06-26 Novozymes, Inc. Methods for producing heterologous polypeptides in mutants of trichoderma
EP2938628A4 (en) 2012-12-24 2016-10-19 Novozymes As POLYPEPTIDES WITH ENDOGLUCANASE ACTIVITY AND POLYNUCLEOTIDES FOR CODING THEREOF
EP3321360A3 (en) 2013-01-03 2018-06-06 Novozymes A/S Alpha-amylase variants and polynucleotides encoding same
CN105051180B (zh) 2013-01-18 2020-06-12 科德克希思公司 用于碳青霉烯类合成的工程化的生物催化剂
DK3202900T3 (en) 2013-02-04 2019-04-08 Dsm Ip Assets Bv CARBOHYDRATE DEGRADING POLYPEPTIDE AND APPLICATIONS THEREOF
WO2014122161A2 (en) 2013-02-06 2014-08-14 Novozymes A/S Polypeptides having protease activity
SI2961844T1 (sl) 2013-02-28 2018-11-30 Codexis, Inc. Spremenjeni polipeptidi transaminaze za industrijsko biokatalizo
CN105164254B (zh) 2013-03-08 2019-06-28 诺维信公司 纤维二糖水解酶变体和编码它们的多核苷酸
CN105164247A (zh) 2013-03-15 2015-12-16 帝斯曼知识产权资产管理有限公司 嗜热性核酸酶用于降解核酸的用途
WO2014145768A2 (en) 2013-03-15 2014-09-18 Bp Corporation North America Inc. Use of non-fungal 5' utrs in filamentous fungi
MX360759B (es) 2013-03-21 2018-11-15 Novozymes As Polipeptidos con actividades lipasa y polinucleotidos que los codifican.
DK2976423T3 (en) 2013-03-21 2019-03-18 Novozymes As Polypeptides with phospholipase A activity and polynucleotides encoding them
US20160060660A1 (en) 2013-04-05 2016-03-03 Université Du Luxembourg Biotechnological production of itaconic acid
WO2014170218A1 (en) 2013-04-18 2014-10-23 Novozymes A/S Polypeptides having protease activity and polynucleotides encoding same
KR102218930B1 (ko) 2013-04-18 2021-02-23 코덱시스, 인코포레이티드 조작된 페닐알라닌 암모니아 리아제 폴리펩티드
DK3372680T3 (da) 2013-04-30 2021-01-11 Novozymes As Glucoamylasevarianter og polynukleotider, som koder for dem
WO2014177541A2 (en) 2013-04-30 2014-11-06 Novozymes A/S Glucoamylase variants and polynucleotides encoding same
CN105283546A (zh) 2013-05-10 2016-01-27 诺维信公司 具有木聚糖酶活性的多肽以及对其进行编码的多核苷酸
CN105209612A (zh) 2013-05-14 2015-12-30 诺维信公司 洗涤剂组合物
EP2997143A1 (en) 2013-05-17 2016-03-23 Novozymes A/S Polypeptides having alpha amylase activity
EP3786269A1 (en) 2013-06-06 2021-03-03 Novozymes A/S Alpha-amylase variants and polynucleotides encoding same
WO2014202622A2 (en) 2013-06-19 2014-12-24 Dsm Ip Assets B.V. Rasamsonia gene and use thereof
WO2014202620A2 (en) 2013-06-19 2014-12-24 Dsm Ip Assets B.V. Rasamsonia gene and use thereof
WO2014202624A2 (en) 2013-06-19 2014-12-24 Dsm Ip Assets B.V. Rasamsonia gene and use thereof
WO2014202621A1 (en) 2013-06-20 2014-12-24 Dsm Ip Assets B.V. Carbohydrate degrading polypeptide and uses thereof
US20160152925A1 (en) 2013-07-04 2016-06-02 Novozymes A/S Polypeptides Having Anti-Redeposition Effect and Polynucleotides Encoding Same
EP3019603A1 (en) 2013-07-09 2016-05-18 Novozymes A/S Polypeptides with lipase activity and polynucleotides encoding same
CA2916905A1 (en) 2013-07-10 2015-01-15 Novartis Ag Multiple proteases deficient filamentous fungal cells and methods of use thereof
DK3022300T3 (en) 2013-07-17 2018-10-22 Novozymes As : Pullulan chimeras and polynucleotides encoding them
BR112016001704A2 (pt) 2013-07-26 2017-09-19 Biomethodes Variante de endoglucanase i, ácido nucleico, vetor ou cassete de expressão, célula hospedeira, método de produção de uma variante de endoglucanase i, método de conversão de biomassa celulósica a açúcares monoméricos, e, método de produção de um produto de fermentação a partir da biomassa celulósica
WO2015022429A1 (en) 2013-08-15 2015-02-19 Novozymes A/S Polypeptides having beta-1,3-galactanase activity and polynucleotides encoding same
US9708630B1 (en) 2013-10-08 2017-07-18 Wisconsin Alumni Research Foundation Cells and methods for producing fatty alcohols
WO2015059133A1 (en) 2013-10-22 2015-04-30 Novozymes A/S Cellobiose dehydrogenase variants and polynucleotides encoding same
CN111851077A (zh) 2013-10-25 2020-10-30 诺维信公司 具有内切葡聚糖酶活性的多肽以及对其进行编码的多核苷酸
CN106232619B (zh) 2013-11-13 2022-09-09 科德克希思公司 工程化的亚胺还原酶和用于酮和胺化合物的还原胺化的方法
EP3074513A1 (en) 2013-11-26 2016-10-05 Novozymes A/S Enzyme compositions and uses thereof
EP2876156A1 (en) 2013-11-26 2015-05-27 Commissariat A L'energie Atomique Et Aux Energies Alternatives New enzymes and method for preparing hydroxylated L-lysine or L-ornithine and analogs thereof
EP3074509B1 (en) 2013-11-29 2019-03-06 Novozymes A/S Peroxygenase variants
EP3077517B1 (en) 2013-12-02 2018-10-17 DSM IP Assets B.V. Ice structuring protein
WO2015085920A1 (en) 2013-12-11 2015-06-18 Novozymes A/S Cutinase variants and polynucleotides encoding same
EP2886656A1 (en) 2013-12-18 2015-06-24 Commissariat A L'energie Atomique Et Aux Energies Alternatives New enzyme and method for preparing 4-hydroxyl benzyl alcohol and derivatives thereof
EP3453757B1 (en) 2013-12-20 2020-06-17 Novozymes A/S Polypeptides having protease activity and polynucleotides encoding same
WO2015109972A1 (en) 2014-01-22 2015-07-30 Novozymes A/S Polypeptides with lipase activity and polynucleotides encoding same
DK3097192T3 (en) 2014-01-22 2018-11-19 Novozymes As PULLULANASE VARIATIONS AND POLYNUCLEOTIDES CODING THEM
EP3114272A1 (en) 2014-03-05 2017-01-11 Novozymes A/S Compositions and methods for improving properties of cellulosic textile materials with xyloglucan endotransglycosylase
US20170027167A1 (en) 2014-03-05 2017-02-02 Novozymes Bioag A/S Formulations comprising polymeric xyloglucan as a carrier for agriculturally beneficial agents
US10123535B2 (en) 2014-03-05 2018-11-13 Novozymes A/S Compositions and methods for improving post-harvest properties of agricultural crops
US20170073890A1 (en) 2014-03-05 2017-03-16 Novozymes A/S Compositions and Methods for Functionalizing and Linking Materials
WO2015134729A1 (en) 2014-03-05 2015-09-11 Novozymes A/S Compositions and methods for improving properties of non-cellulosic textile materials with xyloglucan endotransglycosylase
US10155935B2 (en) 2014-03-12 2018-12-18 Novozymes A/S Polypeptides with lipase activity and polynucleotides encoding same
US20170015950A1 (en) 2014-04-01 2017-01-19 Novozymes A/S Polypeptides having alpha amylase activity
EP3129478B1 (en) 2014-04-10 2019-03-27 Novozymes A/S Alpha-amylase variants and polynucleotides encoding same
US10131863B2 (en) 2014-04-11 2018-11-20 Novozymes A/S Detergent composition
EP3131921B1 (en) 2014-04-15 2020-06-10 Novozymes A/S Polypeptides with lipase activity and polynucleotides encoding same
EP3928787A1 (en) 2014-04-16 2021-12-29 Codexis, Inc. Engineered tyrosine ammonia lyase
WO2015177171A1 (en) 2014-05-19 2015-11-26 Dsm Ip Assets B.V. Proline-specific endoprotease
WO2015177152A1 (en) 2014-05-19 2015-11-26 Dsm Ip Assets B.V. Proline-specific endoprotease
WO2015177153A1 (en) 2014-05-19 2015-11-26 Dsm Ip Assets B.V. Proline-specific endoprotease
CN106459937A (zh) 2014-05-27 2017-02-22 诺维信公司 用于产生脂肪酶的方法
EP3760713A3 (en) 2014-05-27 2021-03-31 Novozymes A/S Lipase variants and polynucleotides encoding same
CA2950273C (en) 2014-05-30 2022-06-21 Novozymes A/S Variants of gh family 11 xylanase and polynucleotides encoding same
MY182924A (en) 2014-06-06 2021-02-05 Novozymes As Enzyme compositions and uses thereof
ES2712402T3 (es) 2014-06-25 2019-05-13 Novozymes As Variantes de xilanasa y polinucleótidos que las codifican
US9708587B2 (en) 2014-07-09 2017-07-18 Codexis, Inc. P450-BM3 variants with improved activity
AU2015293949B2 (en) 2014-07-21 2019-07-25 Teknologian Tutkimuskeskus Vtt Oy Production of glycoproteins with mammalian-like N-glycans in filamentous fungi
US20170267980A1 (en) 2014-08-20 2017-09-21 Novozymes A/S Xyloglucan Endotransglycosylase variants and Polynucleotides Encoding Same
US11390898B2 (en) 2014-09-05 2022-07-19 Novozymes A/S Polypeptides having cellobiohydrolase activity and polynucleotides encoding same
ES2743515T3 (es) 2014-10-23 2020-02-19 Novozymes As Variantes de glucoamilasa y polinucleótidos que codifican las mismas
US10287562B2 (en) 2014-11-20 2019-05-14 Novoszymes A/S Alicyclobacillus variants and polynucleotides encoding same
SG11201703258PA (en) 2014-11-25 2017-05-30 Codexis Inc Engineered imine reductases and methods for the reductive amination of ketone and amine compounds
WO2016090059A1 (en) 2014-12-02 2016-06-09 Novozymes A/S Laccase variants and polynucleotides encoding same
MX2017007103A (es) 2014-12-05 2017-08-24 Novozymes As Variantes de lipasa y polinucleotidos que las codifican.
US20180000076A1 (en) 2014-12-16 2018-01-04 Novozymes A/S Polypeptides Having N-Acetyl Glucosamine Oxidase Activity
WO2016100910A1 (en) 2014-12-19 2016-06-23 Novozymes A/S Recombinant host cells for the production of 3-hydroxypropionic acid
CN114717217A (zh) 2014-12-19 2022-07-08 诺维信公司 包括具有木聚糖酶活性的多肽和具有阿拉伯呋喃糖苷酶活性的多肽的组合物
LT3237621T (lt) 2014-12-22 2023-09-25 Codexis, Inc. Žmogaus alfa-galaktozidazės variantai
DK3242950T3 (da) 2015-01-06 2021-12-20 Dsm Ip Assets Bv Crispr-cas-system til en trådformet svampeværtscelle
EP3256577B1 (en) 2015-02-10 2020-08-26 Codexis, Inc. Ketoreductase polypeptides for the synthesis of chiral compounds
WO2016138167A2 (en) 2015-02-24 2016-09-01 Novozymes A/S Cellobiohydrolase variants and polynucleotides encoding same
DK3262161T3 (da) 2015-02-27 2021-09-13 Novozymes As Rekombinante værtsceller til fremstilling af 3-hydroxypropionsyre
DK3268482T3 (da) 2015-03-09 2020-03-09 Novozymes As Fremgangsmåder til indføring af en flerhed af ekspressionskonstruktioner i en eukaryot celle
US20180073017A1 (en) 2015-04-07 2018-03-15 Novozymes A/S Methods for selecting enzymes having enhanced activity
EP3280818A2 (en) 2015-04-07 2018-02-14 Novozymes A/S Methods for selecting enzymes having lipase activity
AR104205A1 (es) 2015-04-09 2017-07-05 Dsm Ip Assets Bv Fosfolipasa c
EP3292136B1 (en) 2015-05-07 2021-02-17 Codexis, Inc. Penicillin-g acylases
US9920102B2 (en) 2015-05-15 2018-03-20 Albert Einstein College Of Medicine, Inc. Fusion tags for protein expression
AU2016266933A1 (en) 2015-05-22 2017-10-26 Dupont Nutrition Biosciences Aps Acetolactate decarboxylase
CN116676293A (zh) 2015-05-27 2023-09-01 国投生物科技投资有限公司 具有纤维二糖水解酶活性的多肽以及对其进行编码的多核苷酸
NZ737305A (en) 2015-06-02 2021-07-30 Dsm Ip Assets Bv Use of ice structuring protein afp19 expressed in filamentous fungal strains for preparing food
WO2016202739A1 (en) 2015-06-16 2016-12-22 Novozymes A/S Polypeptides with lipase activity and polynucleotides encoding same
CA2981342A1 (en) 2015-06-18 2016-12-22 Novozymes A/S Polypeptides having trehalase activity and the use thereof in process of producing fermentation products
US10392742B2 (en) 2015-06-26 2019-08-27 Novozymes A/S Biofinishing system
WO2016207384A1 (en) 2015-06-26 2016-12-29 Novozymes A/S Method for producing a coffee extract
WO2016207373A1 (en) 2015-06-26 2016-12-29 Novozymes A/S Polypeptides having peroxygenase activity
CA2987160C (en) 2015-07-01 2022-12-13 Novozymes A/S Methods of reducing odor
AU2016286612B2 (en) 2015-07-02 2021-01-28 Novozymes A/S Animal feed compositions and uses thereof
CN107969136B (zh) 2015-07-06 2021-12-21 诺维信公司 脂肪酶变体以及编码它们的多核苷酸
EP3319987B1 (en) 2015-07-07 2021-05-05 Codexis, Inc. Novel p450-bm3 variants with improved activity
US20180216089A1 (en) 2015-07-24 2018-08-02 Novozymes, Inc. Polypeptides Having Beta-Xylosidase Activity And Polynucleotides Encoding Same
CN108138153A (zh) 2015-07-24 2018-06-08 诺维信股份有限公司 具有阿拉伯呋喃糖苷酶活性的多肽以及编码它们的多核苷酸
US20180230446A1 (en) 2015-07-29 2018-08-16 Abengoa Bioenergía Nuevas Tecnologías, S.A. Expression of recombinant beta-xylosidase enzymes
EP3341475A1 (en) 2015-08-24 2018-07-04 Novozymes A/S Beta-alanine aminotransferases for the production of 3-hydroxypropionic acid
WO2017040499A1 (en) 2015-09-02 2017-03-09 Dupont Nutrition Biosciences Aps Glycoside hydolases and their use in preventing and/or treating a pathogenic infection in an animal
EP3344761A1 (en) 2015-09-04 2018-07-11 Novozymes A/S Methods of inhibiting aa9 lytic polysaccharide monooxygenase catalyzed inactivation of enzyme compositions
CN108350443B (zh) 2015-09-17 2022-06-28 诺维信公司 具有黄原胶降解活性的多肽以及编码它们的多核苷酸
CN108350044B (zh) 2015-09-22 2022-05-24 诺维信公司 具有纤维二糖水解酶活性的多肽以及对其进行编码的多核苷酸
WO2017050652A1 (en) 2015-09-25 2017-03-30 Dsm Ip Assets B.V. Asparaginase
WO2017060493A1 (en) 2015-10-07 2017-04-13 Novozymes A/S Polypeptides
EP3362574B1 (en) 2015-10-14 2021-07-07 Novozymes A/S Glucoamylase variants and polynucleotides encoding same
CN108291215A (zh) 2015-10-14 2018-07-17 诺维信公司 具有蛋白酶活性的多肽以及编码它们的多核苷酸
EP4324919A2 (en) 2015-10-14 2024-02-21 Novozymes A/S Polypeptide variants
WO2017070219A1 (en) 2015-10-20 2017-04-27 Novozymes A/S Lytic polysaccharide monooxygenase (lpmo) variants and polynucleotides encoding same
WO2017075426A1 (en) 2015-10-30 2017-05-04 Novozymes A/S Polynucleotide constructs for in vitro and in vivo expression
EP3380608A1 (en) 2015-11-24 2018-10-03 Novozymes A/S Polypeptides having protease activity and polynucleotides encoding same
WO2017093318A1 (en) 2015-12-01 2017-06-08 Novozymes A/S Methods for producing lipases
JP2019500338A (ja) 2015-12-02 2019-01-10 アンスティテュー・ナシオナル・ドゥ・ラ・ルシェルシュ・アグロノミクＩｎｓｔｉｔｕｔ Ｎａｔｉｏｎａｌ Ｄｅ Ｌａ Ｒｅｃｈｅｒｃｈｅ Ａｇｒｏｎｏｍｉｑｕｅ 抗菌活性を有する新規ペプチド及びペプチド中におけるｌ型残基をｄ型アミノ酸に変換することができる新規酵素
CN108431204A (zh) 2015-12-22 2018-08-21 阿尔布梅迪克斯医疗有限公司 改良的表达蛋白质的菌株
WO2017114891A1 (en) 2015-12-30 2017-07-06 Novozymes A/S Enzyme variants and polynucleotides encoding the same
JP2019504625A (ja) 2016-01-29 2019-02-21 ノボザイムス アクティーゼルスカブ β−グルカナーゼ変異体およびこれをコードするポリヌクレオチド
WO2017140807A1 (en) 2016-02-16 2017-08-24 Monaghan Mushrooms Group Fungal polypeptides having lysozyme activity
EP3420104A1 (en) 2016-02-23 2019-01-02 Novozymes A/S Improved next-generation sequencing
CN109415712A (zh) 2016-03-02 2019-03-01 诺维信公司 纤维二糖水解酶变体和编码它们的多核苷酸
EP4095152A3 (en) 2016-03-04 2022-12-28 Danisco US Inc. Engineered ribosomal promoters for protein production in microorganisms
DK3433358T3 (da) 2016-03-24 2022-09-26 Novozymes As Cellobiohydrolasevarianter og polynukleotider, der koder for dem
CN109312333A (zh) 2016-04-07 2019-02-05 诺维信公司 选择具有蛋白酶活性的酶的方法
DK3445776T3 (da) 2016-04-19 2021-04-19 Novozymes As RLMA-inaktiveret filamentøs svampeværtscelle
WO2017186943A1 (en) 2016-04-29 2017-11-02 Novozymes A/S Detergent compositions and uses thereof
CN109415421B (zh) 2016-05-03 2023-02-28 诺维信公司 α-淀粉酶变体以及编码它们的多核苷酸
KR102382489B1 (ko) 2016-05-05 2022-04-01 코덱시스, 인코포레이티드 페니실린 ｇ 아실라제
CN109312319B (zh) 2016-05-09 2023-05-16 诺维信公司 具有改善的性能的变体多肽及其用途
EP3246401A1 (en) 2016-05-20 2017-11-22 Commissariat À L'Énergie Atomique Et Aux Énergies Alternatives New fatty acid decarboxylase and its uses
EP3464579A1 (en) 2016-05-24 2019-04-10 Novozymes A/S Compositions comprising polypeptides having galactanase activity and polypeptides having beta-galactosidase activity
US11058129B2 (en) 2016-05-24 2021-07-13 Novozymes A/S Animal feed additives
EP3464580A1 (en) 2016-05-24 2019-04-10 Novozymes A/S Compositions comprising polypeptides having galactanase activity and polypeptides having beta-galactosidase activity
BR112018073875A2 (pt) 2016-05-24 2019-02-26 Novozymes As polipeptídeo isolado, composição, grânulo, aditivo de ração animal, formulação líquida, ração animal, métodos para liberar galactose de material à base de planta, para melhorar um ou mais parâmetros de desempenho de um animal e o valor nutricional de uma ração animal, para preparar uma ração animal e para produzir o polipeptídeo, uso, polinucleotídeo, construto de ácido nucleico ou vetor de expressão, e, célula hospedeira recombinante.
WO2017205535A1 (en) 2016-05-27 2017-11-30 Novozymes, Inc. Polypeptides having endoglucanase activity and polynucleotides encoding same
WO2017211803A1 (en) 2016-06-07 2017-12-14 Novozymes A/S Co-expression of heterologous polypeptides to increase yield
SG11201809575TA (en) 2016-06-09 2018-11-29 Codexis Inc Biocatalysts and methods for hydroxylation of chemical compounds
DK3469076T3 (da) 2016-06-10 2020-11-16 Dsm Ip Assets Bv Mutant lipase og anvendelse deraf
WO2017218325A1 (en) 2016-06-15 2017-12-21 Codexis, Inc. Engineered beta-glucosidases and glucosylation methods
US10421951B2 (en) 2016-06-22 2019-09-24 Wisconsin Alumni Research Foundation Gene construct encoding mutant thioesterase, mutant thioesterase encoded thereby, transformed host cell containing the gene construct, and method of using them to produce medium-chain fatty acids
EP3825399A1 (en) 2016-06-30 2021-05-26 Danisco US Inc. Aspartic proteases
ES2807212T3 (es) 2016-06-30 2021-02-22 Fornia Biosolutions Inc Nuevas fitasas y usos de las mismas
WO2018002261A1 (en) 2016-07-01 2018-01-04 Novozymes A/S Detergent compositions
WO2018007435A1 (en) 2016-07-05 2018-01-11 Novozymes A/S Pectate lyase variants and polynucleotides encoding same
CN109312353A (zh) 2016-07-06 2019-02-05 诺维信公司 通过crispr-抑制来改善微生物
WO2018007573A1 (en) 2016-07-08 2018-01-11 Novozymes A/S Detergent compositions with galactanase
JP2019524081A (ja) 2016-07-08 2019-09-05 ノボザイムス アクティーゼルスカブ キシラナーゼ変異体およびそれをコードするポリヌクレオチド
BR112019000125A2 (pt) 2016-07-08 2019-07-09 Novozymes As grânulo, polipeptídeo isolado, composição, aditivo de ração animal, ração animal peletizada, métodos de aprimoramento de um ou mais parâmetros de desempenho de um animal, de preparação de uma ração animal, para aprimorar o valor nutricional de uma ração animal, de solubilização de xilana a partir do material à base de planta e de produção do polipeptídeo, polinucleotídeo, construto de ácido nucleico ou vetor de expressão, célula hospedeira recombinante, e, uso do grânulo
WO2018011276A1 (en) 2016-07-13 2018-01-18 The Procter & Gamble Company Bacillus cibi dnase variants and uses thereof
EP4357453A2 (en) 2016-07-18 2024-04-24 Novozymes A/S Lipase variants, polynucleotides encoding same and the use thereof
WO2018017792A1 (en) 2016-07-20 2018-01-25 Novozymes A/S Heat-stable metagenomic carbonic anhydrases and their use
WO2018015303A1 (en) 2016-07-21 2018-01-25 Novozymes A/S Serine protease variants and polynucleotides encoding same
CN109642225A (zh) 2016-07-21 2019-04-16 诺维信公司 丝氨酸蛋白酶变体以及对其进行编码的多核苷酸
CN109476714A (zh) 2016-07-22 2019-03-15 诺维信公司 改善的丝状真菌宿主
WO2018015444A1 (en) 2016-07-22 2018-01-25 Novozymes A/S Crispr-cas9 genome editing with multiple guide rnas in filamentous fungi
WO2018026868A1 (en) 2016-08-01 2018-02-08 Novozymes, Inc. Polypeptides having endoglucanase activity and polynucleotides encoding same
WO2018037062A1 (en) 2016-08-24 2018-03-01 Novozymes A/S Gh9 endoglucanase variants and polynucleotides encoding same
EP3504331A1 (en) 2016-08-24 2019-07-03 Henkel AG & Co. KGaA Detergent compositions comprising xanthan lyase variants i
CA3032248A1 (en) 2016-08-24 2018-03-01 Novozymes A/S Xanthan lyase variants and polynucleotides encoding same
WO2018037065A1 (en) 2016-08-24 2018-03-01 Henkel Ag & Co. Kgaa Detergent composition comprising gh9 endoglucanase variants i
IL264686B1 (en) 2016-08-26 2024-03-01 Codexis Inc Engineered imine reductases and methods for reversible amination of ketone and amine compounds
EP3512953A1 (en) 2016-09-15 2019-07-24 Novozymes A/S Genomic integration of dna fragments in fungal host cells
US11578316B2 (en) 2016-09-16 2023-02-14 Dupont Nutrition Biosciences Aps Acetolactate decarboxylase variants having improved specific activity
EP3532592A1 (en) 2016-10-25 2019-09-04 Novozymes A/S Detergent compositions
WO2018094181A1 (en) 2016-11-21 2018-05-24 Novozymes A/S Yeast cell extract assisted construction of dna molecules
AU2018205718B2 (en) 2017-01-05 2023-09-28 Codexis, Inc. Penicillin-G acylases
CA3051426C (en) 2017-02-01 2023-10-17 The Procter & Gamble Company Cleaning compositions comprising amylase variants
EP3577219B1 (en) 2017-02-01 2023-08-23 Novozymes A/S Alpha-amylase variants
WO2018144679A2 (en) 2017-02-03 2018-08-09 Codexis, Inc. Engineered glycosyltransferases and steviol glycoside glucosylation methods
JP2020505942A (ja) 2017-02-13 2020-02-27 コデクシス， インコーポレイテッド フェニルアラニンアンモニアリアーゼポリペプチド
CA3051770A1 (en) 2017-02-20 2018-08-23 Novozymes A/S Lipolytic enzyme for use in baking
US20200071685A1 (en) 2017-03-06 2020-03-05 Dupont Nutrition Biosciences Aps Novel fungal fucosidases and their use in preventing and/or treating a pathogenic infection in an animal
US20200063166A1 (en) 2017-03-13 2020-02-27 Dsm Ip Assets B.V. Zinc binuclear cluster transcriptional regulator-deficient strain
WO2018167153A1 (en) 2017-03-17 2018-09-20 Novozymes A/S Improved filamentous fungal host cell
WO2018172155A1 (en) 2017-03-23 2018-09-27 Novozymes A/S Improved filamentous fungal host cells
WO2018177938A1 (en) 2017-03-31 2018-10-04 Novozymes A/S Polypeptides having dnase activity
CN110651039A (zh) 2017-03-31 2020-01-03 诺维信公司 具有rna酶活性的多肽
WO2018177936A1 (en) 2017-03-31 2018-10-04 Novozymes A/S Polypeptides having dnase activity
BR112019020772A2 (pt) 2017-04-03 2020-04-28 Novozymes As processo de recuperação
CN110651029B (zh) 2017-04-04 2022-02-15 诺维信公司 糖基水解酶
US20200109352A1 (en) 2017-04-04 2020-04-09 Novozymes A/S Polypeptide compositions and uses thereof
WO2018185150A1 (en) 2017-04-04 2018-10-11 Novozymes A/S Polypeptides
MX2019011900A (es) 2017-04-11 2019-12-05 Novozymes As Variantes de glucoamilasa y polinucleotidos que las codifican.
EP3615058A4 (en) 2017-04-27 2021-06-02 Codexis, Inc. KETOREDUCTASE-POLYPEPTIDES AND POLYNUCLEOTIDES
WO2018202846A1 (en) 2017-05-05 2018-11-08 Novozymes A/S Compositions comprising lipase and sulfite
EP3401385A1 (en) 2017-05-08 2018-11-14 Henkel AG & Co. KGaA Detergent composition comprising polypeptide comprising carbohydrate-binding domain
CA3058092A1 (en) 2017-05-08 2018-11-15 Novozymes A/S Mannanase variants and polynucleotides encoding same
WO2018206535A1 (en) 2017-05-08 2018-11-15 Novozymes A/S Carbohydrate-binding domain and polynucleotides encoding the same
CA3058095A1 (en) 2017-05-08 2018-11-15 Novozymes A/S Mannanase variants and polynucleotides encoding same
CA3062550A1 (en) 2017-05-08 2018-11-15 Codexis, Inc. Engineered ligase variants
CN111032682B (zh) 2017-06-14 2024-04-12 科德克希思公司 用于工业生物催化的工程化转氨酶多肽
KR102638505B1 (ko) 2017-06-20 2024-02-20 알부메딕스 리미티드 개선된 단백질 발현 스트레인
EP3642339A1 (en) 2017-06-22 2020-04-29 Novozymes A/S Xylanase variants and polynucleotides encoding same
EP3645713A4 (en) 2017-06-27 2021-06-30 Codexis, Inc. PENICILLIN G ACYLASES
US11584783B2 (en) 2017-06-28 2023-02-21 Novozymes A/S Processes for producing a fermentation product
CA3066767A1 (en) 2017-06-30 2019-01-03 Codexis, Inc. T7 rna polymerase variants
WO2019005540A1 (en) 2017-06-30 2019-01-03 Codexis, Inc. T7 POLYMERASE RNA VARIANTS
JP7391827B2 (ja) 2017-07-24 2023-12-05 ノボザイムス アクティーゼルスカブ 湿式製粉におけるｇｈ５及びｇｈ３０
MX2020001058A (es) 2017-07-28 2020-08-06 Univ Princeton Marcadores de fusión para expresión de proteínas recombinantes.
US10081800B1 (en) 2017-08-03 2018-09-25 Fornia Biosolutions, Inc. Lactonase enzymes and methods of using same
US11220679B2 (en) 2017-08-08 2022-01-11 Novozymes A/S Polypeptides having trehalase activity
WO2019038059A1 (en) 2017-08-24 2019-02-28 Henkel Ag & Co. Kgaa DETERGENT COMPOSITIONS COMPRISING GH9 ENDOGLUCANASE VARIANTS II
EP3673058A1 (en) 2017-08-24 2020-07-01 Novozymes A/S Gh9 endoglucanase variants and polynucleotides encoding same
WO2019038057A1 (en) 2017-08-24 2019-02-28 Novozymes A/S VARIANTS OF XANTHANE LYASE AND POLYNUCLEOTIDES ENCODING THE SAME
WO2019038060A1 (en) 2017-08-24 2019-02-28 Henkel Ag & Co. Kgaa DETERGENT COMPOSITION COMPRISING XANTHANE LYASE II VARIANTS
EP3675646A1 (en) 2017-09-01 2020-07-08 Novozymes A/S Animal feed additives comprising polypeptide having protease activity and uses thereof
WO2019046703A1 (en) 2017-09-01 2019-03-07 Novozymes A/S METHODS OF ENHANCING GENOME EDITION IN FUNGI
CA3070193A1 (en) 2017-09-01 2019-03-07 Novozymes A/S Animal feed additives comprising a polypeptide having protease activity and uses thereof
WO2019063614A1 (en) 2017-09-26 2019-04-04 Bunge Global Innovation, Llc. ENZYMATIC REMOVAL OF CHLOROPHYLLIC SUBSTRATES FROM TRIACYLGLYCEROL OILS
CN111108195A (zh) 2017-09-27 2020-05-05 宝洁公司 包含脂肪酶的洗涤剂组合物
US11332725B2 (en) 2017-09-27 2022-05-17 Novozymes A/S Lipase variants and microcapsule compositions comprising such lipase variants
US11732221B2 (en) 2017-10-02 2023-08-22 Novozymes A/S Polypeptides having mannanase activity and polynucleotides encoding same
WO2019068713A1 (en) 2017-10-02 2019-04-11 Novozymes A/S POLYPEPTIDES HAVING MANNANASE ACTIVITY AND POLYNUCLEOTIDES ENCODING THESE POLYPEPTIDES
EP3701016A1 (en) 2017-10-27 2020-09-02 Novozymes A/S Dnase variants
HUE057471T2 (hu) 2017-10-27 2022-05-28 Procter & Gamble Polipeptid-variánsokat tartalmazó mosószerkészítmények
DE102017125559A1 (de) 2017-11-01 2019-05-02 Henkel Ag & Co. Kgaa Reinigungszusammensetzungen, die dispersine ii enthalten
DE102017125558A1 (de) 2017-11-01 2019-05-02 Henkel Ag & Co. Kgaa Reinigungszusammensetzungen, die dispersine i enthalten
DE102017125560A1 (de) 2017-11-01 2019-05-02 Henkel Ag & Co. Kgaa Reinigungszusammensetzungen, die dispersine iii enthalten
SG11202003094PA (en) 2017-11-07 2020-05-28 Codexis Inc Transglutaminase variants
WO2019092042A1 (en) 2017-11-10 2019-05-16 Novozymes A/S Temperature-sensitive cas9 protein
WO2019096903A1 (en) 2017-11-20 2019-05-23 Novozymes A/S New galactanases (ec 3.2.1.89) for use in soy processing
EP3485734A1 (en) 2017-11-21 2019-05-22 Technische Universität München Method for preparing food products comprising rye
EP3488854A1 (en) 2017-11-22 2019-05-29 Technische Universität München Method for preparing xyloglucan-oligosaccharides
US11725197B2 (en) 2017-12-04 2023-08-15 Novozymes A/S Lipase variants and polynucleotides encoding same
AU2018383752A1 (en) 2017-12-13 2020-05-21 Codexis, Inc. Carboxyesterase polypeptides for amide coupling
US11408009B2 (en) 2017-12-18 2022-08-09 Whitehead Institute For Biomedical Research Host cell expression of 4-hydroxyphenylacetaldehyde synthase for production of salidroside, icariside D2, and precursors
EP3502242A1 (en) 2017-12-20 2019-06-26 Technische Universität München New xylanase with improved thermostability and increased enzyme activity on arabinoxylan
US20210017544A1 (en) 2017-12-22 2021-01-21 Novozymes A/S Counter-Selection by Inhibition of Conditionally Essential Genes
EP3749761A1 (en) 2018-02-08 2020-12-16 Novozymes A/S Lipases, lipase variants and compositions thereof
US20210071156A1 (en) 2018-02-08 2021-03-11 Novozymes A/S Lipase Variants and Compositions Thereof
EP3755809A1 (en) 2018-02-23 2020-12-30 Novozymes A/S Long non-coding rna-expression in fungal hosts
EP3530744A1 (en) 2018-02-23 2019-08-28 University of Limerick A polypeptide having xylanase and/or cellulase activity
CN112004931A (zh) 2018-03-26 2020-11-27 诺维信公司 真菌伴侣蛋白
WO2019185726A1 (en) 2018-03-29 2019-10-03 Novozymes A/S Mannanase variants and polynucleotides encoding same
EP3775191A1 (en) 2018-04-09 2021-02-17 Novozymes A/S Polypeptides having alpha-amylase activity and polynucleotides encoding same
EP3781680A1 (en) 2018-04-19 2021-02-24 Novozymes A/S Stabilized cellulase variants
CN112272701A (zh) 2018-04-19 2021-01-26 诺维信公司 稳定化的纤维素酶变体
CN112534050A (zh) 2018-05-18 2021-03-19 帝斯曼知识产权资产管理有限公司 突变体脂肪酶及其用途
KR20210013585A (ko) 2018-05-18 2021-02-04 디에스엠 아이피 어셋츠 비.브이. 돌연변이체 리파아제 및 이의 용도
EP3807409A4 (en) 2018-06-12 2022-08-03 Codexis, Inc. MODIFIED TYROSINE AMMONIA-LYASE
WO2020002575A1 (en) 2018-06-28 2020-01-02 Novozymes A/S Polypeptides having pectin lyase activity and polynucleotides encoding same
SG11202012107RA (en) 2018-07-09 2021-01-28 Codexis Inc Engineered deoxyribose-phosphate aldolases
US11034948B2 (en) 2018-07-09 2021-06-15 Codexis, Inc. Engineered phosphopentomutase variant enzymes
CA3103718A1 (en) 2018-07-09 2020-01-16 Codexis, Inc. Engineered purine nucleoside phosphorylase variant enzymes
EP3821000A4 (en) 2018-07-09 2022-07-20 Codexis, Inc. GALACTOSE OXIDASE VARIANT ENZYMES OBTAINED BY GENETIC ENGINEERING
MX2021000323A (es) 2018-07-09 2021-03-25 Codexis Inc Enzimas de variante de pantotenato quinasa modificadas geneticamente.
CA3105916A1 (en) 2018-07-12 2020-01-16 Codexis, Inc. Engineered phenylalanine ammonia lyase polypeptides
WO2020012266A1 (en) 2018-07-12 2020-01-16 Novartis Ag Biocatalytic synthesis of olodanrigan (ema401) from 3-(2-(benzyloxy)-3-methoxyphenyl)propenoic acid with phenylalanine ammonia lyase
JP2021532757A (ja) 2018-07-30 2021-12-02 コデクシス， インコーポレイテッド 操作されたグリコシルトランスフェラーゼおよびステビオールグリコシドのグルコシル化方法
EP3830261A1 (en) 2018-08-02 2021-06-09 Novozymes A/S Preparation of combinatorial libraries of dna constructs using introns
BR112021003244A2 (pt) 2018-08-31 2021-05-18 Novozymes A/S polipeptídeo isolado ou purificado, uso, método para melhoria do valor nutricional de uma ração animal, aditivo de ração animal, ração animal, polinucleotídeo isolado ou purificado, construção de ácido nucleico ou vetor de expressão, e, célula hospedeira recombinante
WO2020070199A1 (en) 2018-10-03 2020-04-09 Novozymes A/S Polypeptides having alpha-mannan degrading activity and polynucleotides encoding same
CN113056552A (zh) 2018-10-09 2021-06-29 诺维信公司 经修饰的丝状真菌宿主细胞
KR20210084590A (ko) 2018-10-29 2021-07-07 코덱시스, 인코포레이티드 조작된 dna 중합효소 변이체
EP3874051A1 (en) 2018-10-31 2021-09-08 Novozymes A/S Genome editing by guided endonuclease and single-stranded oligonucleotide
EP3887524A1 (en) 2018-11-28 2021-10-06 Novozymes A/S Modified filamentous fungal host cells
EP3887391A1 (en) 2018-11-28 2021-10-06 Novozymes A/S Improved filamentous fungal host cells
WO2020120420A1 (en) 2018-12-10 2020-06-18 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Method for preparation of primary amine compounds
CN113302305A (zh) 2018-12-12 2021-08-24 诺维信公司 提高丝状真菌细胞在多肽的产生方面的生产力的方法
EP3894551A1 (en) 2018-12-12 2021-10-20 Novozymes A/S Polypeptides having xylanase activity and polynucleotides encoding same
US11473077B2 (en) 2018-12-14 2022-10-18 Codexis, Inc. Engineered tyrosine ammonia lyase
WO2020132252A2 (en) 2018-12-20 2020-06-25 Codexis, Inc. Human alpha-galactosidase variants
CN113366103A (zh) 2018-12-21 2021-09-07 诺维信公司 具有肽聚糖降解活性的多肽以及编码其的多核苷酸
DK3898985T3 (da) 2018-12-21 2023-04-17 Novozymes As Proteinekspression i tandem
EP3908654A1 (en) 2019-01-11 2021-11-17 River Stone Biotech ApS Recombinant host cells with improved production of l-dopa, dopamine, (s)-norcoclaurine or derivatives thereof
WO2020161354A1 (en) 2019-02-08 2020-08-13 Pili Recombinant host cells to produce anthraquinone derivatives
WO2020173817A1 (en) 2019-02-28 2020-09-03 Novozymes A/S Calcite binding proteins
US20230159937A1 (en) 2019-03-08 2023-05-25 Danisco Us Inc Fusion polypeptides
US20220154226A1 (en) 2019-03-18 2022-05-19 Novozymes A/S Polypeptides Having Pullulanase Activity Suitable For Use In Liquefaction
US10995325B2 (en) 2019-03-21 2021-05-04 Fornia Biosolutions, Inc. Additional phytase variants and methods
WO2020198212A1 (en) 2019-03-27 2020-10-01 Bunge Global Innovation, Llc Silica adsorbent treatment for removal of chlorophyll derivatives from triacylglycerol-based oils
WO2020198731A2 (en) 2019-03-28 2020-10-01 Danisco Us Inc Engineered antibodies
US20220169953A1 (en) 2019-04-03 2022-06-02 Novozymes A/S Polypeptides having beta-glucanase activity, polynucleotides encoding same and uses thereof in cleaning and detergent compositions
WO2020207944A1 (en) 2019-04-10 2020-10-15 Novozymes A/S Polypeptide variants
US20220186151A1 (en) 2019-04-12 2022-06-16 Novozymes A/S Stabilized glycoside hydrolase variants
US20220275354A1 (en) 2019-05-15 2022-09-01 Novozymes A/S TEMPERATURE-SENSITIVE RNA- Guided Endonuclease
WO2020239784A1 (en) 2019-05-27 2020-12-03 Octarine Bio Ivs Genetically modified host cells producing glycosylated cannabinoids.
EP3987022A1 (en) 2019-06-24 2022-04-27 Novozymes A/S Alpha-amylase variants
EP3986996A1 (en) 2019-06-24 2022-04-27 The Procter & Gamble Company Cleaning compositions comprising amylase variants
US20220298517A1 (en) 2019-06-25 2022-09-22 Novozymes A/S Counter-selection by inhibition of conditionally essential genes
EP3994255A1 (en) 2019-07-02 2022-05-11 Novozymes A/S Lipase variants and compositions thereof
CN114391038A (zh) 2019-07-25 2022-04-22 诺维信公司 丝状真菌表达系统
EP4004187A1 (en) 2019-07-26 2022-06-01 Novozymes A/S Modified filamentous fungal host cell
WO2021048172A2 (en) 2019-09-09 2021-03-18 River Stone Biotech Aps Delivery vehicle for in situ delivering of pharmaceutical agents
EP4031661A1 (en) 2019-09-16 2022-07-27 Novozymes A/S Polypeptides having beta-glucanase activity and polynucleotides encoding same
US20210094986A1 (en) 2019-09-27 2021-04-01 The Procter & Gamble Company Consumer product compositions comprising fatty acid photodecarboxyalases
US20220340843A1 (en) 2019-10-03 2022-10-27 Novozymes A/S Polypeptides comprising at least two carbohydrate binding domains
US20220389474A1 (en) 2019-10-28 2022-12-08 Danisco Us Inc. Microbial host cells for the production of heterologous cyanuric acid hydrolases and biuret hydrolases
US20210139879A1 (en) 2019-10-31 2021-05-13 The Procter & Gamble Company Consumer Product Compositions Comprising P450 Fatty Acid Decarboxylases
EP4077654A2 (en) 2019-12-19 2022-10-26 Novozymes A/S Xylanase variants and polynucleotides encoding same
US20220411773A1 (en) 2019-12-20 2022-12-29 Novozymes A/S Polypeptides having proteolytic activity and use thereof
US20230242960A1 (en) 2020-01-24 2023-08-03 Novozymes A/S Mutants of a filamentous fungal cell having increased productivity in the production of a polypeptide
WO2021152123A1 (en) 2020-01-31 2021-08-05 Novozymes A/S Mannanase variants and polynucleotides encoding same
EP4097226A1 (en) 2020-01-31 2022-12-07 Novozymes A/S Mannanase variants and polynucleotides encoding same
WO2021163015A1 (en) 2020-02-10 2021-08-19 Novozymes A/S Process for producing ethanol from raw starch using alpha-amylase variants
WO2021163011A2 (en) 2020-02-10 2021-08-19 Novozymes A/S Alpha-amylase variants and polynucleotides encoding same
EP4103709A2 (en) 2020-02-10 2022-12-21 Novozymes A/S Polypeptides having alpha-amylase activity and polynucleotides encoding same
US20230220366A1 (en) 2020-02-26 2023-07-13 Novozymes A/S Polypeptide Variants
WO2021183622A1 (en) 2020-03-12 2021-09-16 Novozymes A/S Crispr-aid using catalytically inactive rna-guided endonuclease
US20230203191A1 (en) 2020-03-30 2023-06-29 Danisco Us Inc Engineered antibodies
EP3892708A1 (en) 2020-04-06 2021-10-13 Henkel AG & Co. KGaA Cleaning compositions comprising dispersin variants
EP4133066A1 (en) 2020-04-08 2023-02-15 Novozymes A/S Carbohydrate binding module variants
US11788071B2 (en) 2020-04-10 2023-10-17 Codexis, Inc. Engineered transaminase polypeptides
WO2021211331A1 (en) 2020-04-13 2021-10-21 Abbott Point Of Care Inc. METHODS, COMPLEXES AND KITS FOR DETECTING OR DETERMINING AN AMOUNT OF A ß-CORONAVIRUS ANTIBODY IN A SAMPLE
US20230167384A1 (en) 2020-04-21 2023-06-01 Novozymes A/S Cleaning compositions comprising polypeptides having fructan degrading activity
EP4153765A1 (en) 2020-05-20 2023-03-29 Wisconsin Alumni Research Foundation Cells and methods for producing methyl ketones
US20220043000A1 (en) 2020-08-04 2022-02-10 Abbott Laboratories Methods and kits for detecting sars-cov-2 protein in a sample
BR112023002578A2 (pt) 2020-08-13 2023-03-14 Novozymes As Variantes de fitase e polinucleotídeos codificando as mesmas
WO2022043321A2 (en) 2020-08-25 2022-03-03 Novozymes A/S Variants of a family 44 xyloglucanase
KR20230145027A (ko) 2020-08-28 2023-10-17 코덱시스, 인코포레이티드 조작된 아밀라제 변이체
CA3191867A1 (en) 2020-08-28 2022-03-03 Codexis, Inc. Engineered protease variants
MX2023002095A (es) 2020-08-28 2023-03-15 Novozymes As Variantes de proteasa con solubilidad mejorada.
US20220112446A1 (en) 2020-10-09 2022-04-14 The Procter & Gamble Company Cleaning composition comprising an alpha-dioxygenase
US20230407273A1 (en) 2020-10-13 2023-12-21 Novozymes A/S Glycosyltransferase variants for improved protein production
BR112023008326A2 (pt) 2020-10-29 2023-12-12 Novozymes As Variantes de lipase e composições compreendendo tais variantes de lipase
WO2022090555A1 (en) 2020-11-02 2022-05-05 Novozymes A/S Leader peptides and polynucleotides encoding the same
MX2023004938A (es) 2020-11-02 2023-05-17 Novozymes As Variantes de glucoamilasa y polinucleotidos que codifican las mismas.
EP4026900A3 (en) 2020-12-17 2022-10-05 Fornia BioSolutions, Inc. Xylanase variants and methods
EP4262804A2 (en) 2020-12-18 2023-10-25 Codexis, Inc. Engineered uridine phosphorylase variant enzymes
EP4023757A1 (en) 2020-12-29 2022-07-06 The Protein Brewery B.V. Methods for generating selection marker-free transformants of heterokaryotic organisms
WO2022147147A1 (en) 2020-12-30 2022-07-07 Abbott Laboratories Methods for determining sars-cov-2 antigen and anti-sars-cov-2 antibody in a sample
AR124921A1 (es) 2021-02-18 2023-05-17 Novozymes As Polipéptidos inactivos que contienen hemo
EP4305146A1 (en) 2021-03-12 2024-01-17 Novozymes A/S Polypeptide variants
CA3199985A1 (en) 2021-03-15 2022-09-22 Lars Lehmann Hylling Christensen Cleaning compositions containing polypeptide variants
EP4060036A1 (en) 2021-03-15 2022-09-21 Novozymes A/S Polypeptide variants
US20240060061A1 (en) 2021-03-15 2024-02-22 Novozymes A/S Dnase variants
IL305919A (en) 2021-04-02 2023-11-01 Codexis Inc A transgenic enzyme variant of adenylate kinase
US20220325284A1 (en) 2021-04-02 2022-10-13 Codexis, Inc. Engineered guanylate kinase variant enzymes
CN117222735A (zh) 2021-04-02 2023-12-12 科德克希思公司 工程化乙酸激酶变体酶
US20220325285A1 (en) 2021-04-02 2022-10-13 Codexis, Inc. ENGINEERED CYCLIC GMP-AMP SYNTHASE (cGAS) VARIANT ENZYMES
AU2022270929A1 (en) 2021-05-07 2023-10-19 River Stone Biotech Aps Glycosylated opioids
BR112023024706A2 (pt) 2021-05-27 2024-02-15 Novozymes As Reguladores da transcrição e polinucleotídeos que os codificam
EP4359518A1 (en) 2021-06-23 2024-05-01 Novozymes A/S Alpha-amylase polypeptides
WO2023006699A1 (en) 2021-07-30 2023-02-02 Københavns Universitet Cells and method for producing isoprenoid molecules with canonical and non-canonical structures
US20230089159A1 (en) 2021-09-16 2023-03-23 The Procter & Gamble Company Cleaning composition comprising an engineered fatty acid alpha-dioxygenase
WO2024015953A1 (en) 2022-07-15 2024-01-18 Danisco Us Inc. Methods for producing monoclonal antibodies

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3937654A (en) * 1970-05-14 1976-02-10 Ranks Hovis Mcdougall Limited Production of edible protein substances
IE35176B1 (en) * 1970-05-14 1975-11-26 Ranks Hovis Mcdougall Ltd Improvements in the production of edible protein containing substances
US4163692A (en) * 1977-04-25 1979-08-07 E. I. Du Pont De Nemours And Company Low phosphate growth of fungal mycelia
US5364770A (en) * 1985-08-29 1994-11-15 Genencor International Inc. Heterologous polypeptides expressed in aspergillus
US4935349A (en) * 1986-01-17 1990-06-19 Zymogenetics, Inc. Expression of higher eucaryotic genes in aspergillus
US5070020A (en) * 1988-05-09 1991-12-03 Eli Lilly And Company Recombinant dna expression vectors and dna compounds that encode deacetoxycephalosporin c synthetase
GB8904762D0 (en) * 1989-03-02 1989-04-12 Glaxo Group Ltd Biological process
GB9011347D0 (en) * 1990-05-21 1990-07-11 Ici Plc Production of a proteinaceous composition
CA2069147A1 (en) * 1991-05-22 1992-11-23 Kazuaki Kitano Dna and its use
FR2681076B1 (fr) * 1991-09-06 1994-11-18 Sanofi Elf Adn recombinant codant pour une proteine a activite endochitinase.
US5360901A (en) * 1992-03-04 1994-11-01 Genencor International, Inc. Gene sequence encoding Aspergillus niger catalase-R

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1318595C (zh) * 1999-01-13 2007-05-30 诺沃奇梅兹有限公司 在缺乏环己缩酚肽的细胞中制备多肽的方法
CN101067127B (zh) * 1999-01-13 2010-12-29 诺沃奇梅兹有限公司 在缺乏环己缩酚肽的细胞中制备多肽的方法

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