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    ENHANCED CITRIC ACID PRODUCTION IN ASPERGILLUS
    3.
    发明申请
    ENHANCED CITRIC ACID PRODUCTION IN ASPERGILLUS 审中-公开
    在ASPERGILLUS中增强柠檬酸生产

    公开(公告)号：WO2013082459A1

    公开(公告)日：2013-06-06

    申请号：PCT/US2012/067349

    申请日：2012-11-30

    Applicant: BATTELLE MEMORIAL INSTITUTE

    Inventor： DAI, Ziyu ,  BAKER, Scott, E.

    IPC: C12N9/10 ,  C12N1/15

    CPC classification number: C12P7/48 ,  C12N1/14 ,  C12N9/1051 ,  C12Y204/01258

    Abstract: Provided herein are fungi, such as Aspergillus niger, having a dolichyl-P- Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase (Alg3) gene genetic inactivation, increased expression of a loss of aflR expression A (Lae), or both. In some examples, such mutants have several phenotypes, including an increased production of citric acid relative to the parental strain. Methods of using the disclosed fungi to make citric acid are also provided, as are compositions and kits including the disclosed fungi.

    Abstract translation: 本文提供的是真菌，例如具有双酰基-P-Man Man（5）GlcNAc（2）-PP-二酰基甘露糖基转移酶（Alg3）基因失活的真菌黑曲霉，增加的aflR表达A（Lae） ， 或两者。 在一些实例中，这样的突变体具有几种表型，包括相对于亲本菌株增加柠檬酸的产生。 还提供了使用所公开的真菌制备柠檬酸的方法，以及包括所公开的真菌的组合物和试剂盒。

    METHOD OF PRODUCING HUMAN GROWTH FACTORS FROM WHOLE PLANTS OR PLANT CELL CULTURES
    4.
    发明申请
    METHOD OF PRODUCING HUMAN GROWTH FACTORS FROM WHOLE PLANTS OR PLANT CELL CULTURES 审中-公开
    从全植物或植物细胞培养物生产人类生长因子的方法

    公开(公告)号：WO1998021348A1

    公开(公告)日：1998-05-22

    申请号：PCT/US1997020603

    申请日：1997-11-12

    Applicant: BATTELLE MEMORIAL INSTITUTE

    Inventor： BATTELLE MEMORIAL INSTITUTE ,  HOOKER, Brian, S. ,  DAI, Ziyu ,  GAO, Jianwei ,  KINGSLEY, Mark, T. ,  WELLER, Richard, E.

    IPC: C12N15/82

    CPC classification number: C12N15/8257 ,  A61K38/00 ,  C07K14/485 ,  C07K2319/00

    Abstract: The production of hEGF is achieved in both whole plants and plant cell culture wherein the hEGF has a length of at least 200 amino acids. For epidermal growth factor this would comprise at least a tetramer of EGF units. Effectiveness or production of the translation process has been increased according to the present invention by (1) cloning of pre-pro-EGF cDNA of approximately 4.5 kb into both whole plants and cell culture to increase overall titers of active hEGF; (2) synthesizing cDNA and transforming plants and cell culture for production of an oligomeric polypeptide consisting of repeated hEGF domains; and (3) increasing the overall size of the gene to be expressed with a fusion construct encoding hEGF linked to a protein that is efficiently produced in plant systems. As needed, synthetic cDNA includes plant-specific proteolytic cleavage sites between EGF repeats to facilitate correct processing in planta. Appropriate proteolytic cleavage sites upstream and downstream of hEGF are added if needed to obtain final product. In whole plants, use of a regulatory element confers hEGF production characteristics into traditionally non-saleable portions of crop plants, such as the leafy tops of potatoes. Use of potato tops under post-harvest conditions, results in overexpression production of hEGF in non-saleable plant portions towards the end of the harvesting season, without affecting crop quality.

    Abstract translation: 在整个植物和植物细胞培养物中实现hEGF的产生，其中hEGF具有至少200个氨基酸的长度。 对于表皮生长因子，这将包括至少四聚体的EGF单元。 根据本发明，翻译过程的有效性或生产已经通过（1）将大约4.5kb的前原EGF cDNA克隆到整个植物和细胞培养物中以增加活性hEGF的总滴度; （2）合成cDNA和转化植物和细胞培养物以产生由重复的hEGF结构域组成的寡聚多肽; 和（3）增加用编码与在植物系统中有效产生的蛋白质连接的hEGF的融合构建体来表达基因的总体大小。 根据需要，合成cDNA包括EGF重复之间的植物特异性蛋白水解切割位点，以促进植物中的正确加工。 如果需要获得最终产品，则加入hEGF上游和下游的合适的蛋白水解切割位点。 在整个植物中，使用调节元件将hEGF生产特征赋予作物植物的传统不可销售部分，例如马铃薯的叶状顶部。 在收获后的条件下使用马铃薯盖，导致在收获季节结束时在非销售植物部分过度表达hEGF，而不影响作物品质。

    ENHANCED ITACONIC ACID PRODUCTION IN ASPERGILLUS WITH INCREASED LAEA EXPRESSION
    5.
    发明申请
    ENHANCED ITACONIC ACID PRODUCTION IN ASPERGILLUS WITH INCREASED LAEA EXPRESSION 审中-公开
    乳酸杆菌表达增强的酪蛋白酸生产

    公开(公告)号：WO2017074533A1

    公开(公告)日：2017-05-04

    申请号：PCT/US2016/046122

    申请日：2016-08-09

    Applicant: BATTELLE MEMORIAL INSTITUTE

    Inventor： DAI, Ziyu ,  BAKER, Scott, E.

    IPC: C12P7/44 ,  C07K14/38

    CPC classification number: C07K14/38 ,  C12P7/44 ,  C12P7/48

    Abstract: Fungi, such as Aspergillus niger , having a dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase ( Alg3 ) gene genetic inactivation, increased expression of a loss of afl R expression A ( LaeA ), or both, are described. In some examples, such mutants have several phenotypes, including an increased production of citric acid relative to the parental strain. Methods of using the disclosed fungi to make citric acid are also described, as are compositions and kits including the disclosed fungi. Further described are Aspergillus terreus fungi overexpressing the LaeA gene and the use of such fungi for the production of itaconic acid. In some instances, the A. terreus fungi also include a genetic inactivation of the Alg3 gene.

    Abstract translation: （5）GlcNAc（2）-PP-dolichyl甘露糖基转移酶（Alg3）的真菌，如黑曲霉（Aspergillus niger） i）基因遗传失活，aflR表达A（LaeA）丧失或两者的增加的表达被描述。 在一些实例中，这样的突变体具有几种表型，包括相对于亲本菌株增加的柠檬酸生产。 还描述了使用公开的真菌制造柠檬酸的方法，以及包括所公开的真菌的组合物和试剂盒。 进一步描述的是过表达LaeA基因的土曲霉真菌和这种真菌用于生产衣康酸的用途。 在某些情况下， 土曲霉真菌还包括Alg3基因的遗传失活。

    PRODUCTION OF HUMAN COAGULATION FACTOR VIII FROM PLANT CELLS AND WHOLE PLANTS
    6.
    发明申请
    PRODUCTION OF HUMAN COAGULATION FACTOR VIII FROM PLANT CELLS AND WHOLE PLANTS 审中-公开
    从植物细胞和全植物生产人类凝血因子VIII

    公开(公告)号：WO2005123928A1

    公开(公告)日：2005-12-29

    申请号：PCT/US2004/018312

    申请日：2004-06-08

    Applicant: BATTELLE MEMORIAL INSTITUTE ,  HOOKER, Brian ,  ANDERSON, Daniel ,  GAO, Johnway ,  DAI, Ziyu

    Inventor： HOOKER, Brian ,  ANDERSON, Daniel ,  GAO, Johnway ,  DAI, Ziyu

    IPC: C12N15/82

    CPC classification number: C12N15/8257 ,  C12N5/04 ,  C12N2510/02

    Abstract: The invention includes methods for production of a polypeptide having factor VIII activity by introduction of a polynucleotide construct into a plant cell. The construct includes an encoding sequence for a polypeptide of coagulation factor VIII or a functional variant thereof. The plant cell is cultured or regenerated into a plant and the polypeptide or functional variant of factor VIII is expressed therein. The invention also includes vectors, plant cells, plant tissues, plants and seeds containing a polynucleotide sequence encoding a functional variant of human coagulation factor VIII. The invention further includes a recombinant DNA molecule having a promoter which is functional in plants operably linked to a coding sequence which codes for a polynucleotide having coagulation factor VIII activity.

    Abstract translation: 本发明包括通过将多核苷酸构建体引入植物细胞来生产具有因子VIII活性的多肽的方法。 该构建体包含凝血因子VIII多肽或其功能变体的编码序列。 将植物细胞培养或再生成植物，并且在其中表达因子VIII的多肽或功能变体。 本发明还包括含有编码人凝血因子VIII功能变体的多核苷酸序列的载体，植物细胞，植物组织，植物和种子。 本发明还包括具有启动子的重组DNA分子，所述启动子在植物中可操作地连接编码具有凝血因子VIII活性的多核苷酸的编码序列。

    ENHANCED CITRIC ACID PRODUCTION IN ASPERGILLUS
    7.
    发明公开
    ENHANCED CITRIC ACID PRODUCTION IN ASPERGILLUS 审中-公开
    的柠檬酸在黑提高了生产

    公开(公告)号：EP2785836A1

    公开(公告)日：2014-10-08

    申请号：EP12854225.5

    申请日：2012-11-30

    Applicant: Battelle Memorial Institute

    Inventor： DAI, Ziyu ,  BAKER, Scott, E.

    IPC: C12N9/10 ,  C12N1/15

    CPC classification number: C12P7/48 ,  C12N1/14 ,  C12N9/1051 ,  C12Y204/01258

    Abstract: Provided herein are fungi, such as Aspergillus niger, having a dolichyl-P- Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase (Alg3) gene genetic inactivation, increased expression of a loss of aflR expression A (Lae), or both. In some examples, such mutants have several phenotypes, including an increased production of citric acid relative to the parental strain. Methods of using the disclosed fungi to make citric acid are also provided, as are compositions and kits including the disclosed fungi.

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