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    Intracellular metabolic flux analysis method using substrate labeled with isotope
    2.
    发明授权
    Intracellular metabolic flux analysis method using substrate labeled with isotope 失效
    使用同位素标记的底物的细胞内代谢通量分析方法

    公开(公告)号：US08510054B2

    公开(公告)日：2013-08-13

    申请号：US11048923

    申请日：2005-02-03

    申请人： Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui

    发明人： Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui

    IPC分类号： G01N33/48 ,  C12Q1/00

    CPC分类号： G01N33/5091 ,  C12Q1/00 ,  G06F19/12

    摘要： A method for intracellular metabolic flux analysis comprising (a) culturing cells in a medium not containing any isotope-labeled substrate to a target phase of the metabolic flux analysis, (b) adding an isotope-labeled substrate to the medium, and continuing culture and collecting samples from the medium in time course, (c) measuring isotope distribution in an intracellular metabolite contained in the samples collected in time course, (d) performing a regression analysis for measured data and calculating an isotope distribution ratio in a steady state, and (e) analyzing a metabolic flux of the cultured cells by using the calculated isotope distribution ratio.

    摘要翻译： 一种用于细胞内代谢通量分析的方法，包括（a）在不含任何同位素标记的底物的培养基中将细胞培养至代谢通量分析的目标阶段，（b）将同位素标记的底物加入到培养基中， 在时间过程中从培养基中收集样品，（c）测量在时间过程中收集的样品中所含的细胞内代谢物中的同位素分布，（d）对稳定状态进行测量数据和计算同位素分布比的回归分析，以及 （e）使用计算出的同位素分布比分析培养细胞的代谢通量。

    METHOD FOR PRODUCTION OF L-AMINO ACID
    4.
    发明申请
    METHOD FOR PRODUCTION OF L-AMINO ACID 有权
    L-氨基酸生产方法

    公开(公告)号：US20090239269A1

    公开(公告)日：2009-09-24

    申请号：US12420934

    申请日：2009-04-09

    申请人： Yoshinori Tajima ,  Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui

    发明人： Yoshinori Tajima ,  Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui

    IPC分类号： C12P13/20 ,  C12P13/08

    CPC分类号： C12N9/88 ,  C12P13/08 ,  C12P13/227

    摘要： A bacterium which belongs to the Enterobacteriaceae family and has an ability to produce an L-amino acid such as L-lysine, L-threonine and L-tryptophan and is modified to enhance glutamic acid decarboxylase activity is cultured in a medium to produce and accumulate the L-amino acid in the medium or cells of the bacterium. Then, the L-amino acid is collected from the medium or the cells.

    摘要翻译： 属于肠杆菌科的具有生产L-赖氨酸，L-苏氨酸和L-色氨酸的L-氨基酸的能力并经过修饰以增强谷氨酸脱羧酶活性的细菌在培养基中培养以产生和积累 细菌的培养基或细胞中的L-氨基酸。 然后，从培养基或细胞收集L-氨基酸。

    Method for simulating a production process of a substance
    6.
    发明申请
    Method for simulating a production process of a substance 审中-公开
    模拟物质生产过程的方法

    公开(公告)号：US20070038419A1

    公开(公告)日：2007-02-15

    申请号：US11501232

    申请日：2006-08-09

    申请人： Yoshihiro Usuda ,  Shintaro Iwatani ,  Kazuhiko Matsui

    发明人： Yoshihiro Usuda ,  Shintaro Iwatani ,  Kazuhiko Matsui

    IPC分类号： G06F17/10

    CPC分类号： G16B5/00

    摘要： A method for simulating a substance production process using cells based on a set of differential equations that represent intracellular metabolites and gene expression comprising including a specific growth rate of cells, expressed as a differential equation, in the set of differential equations; assigning values for parameters in the set of differential equations, wherein at least one of said parameters is represented as a growth rate factor; incorporating in the set of differential equations a formation rate for formation of a cell component, wherein said formation rate is represented as a growth rate factor; incorporating in the set of differential equations an inflow rate of a metabolite taken from outside of the cells and/or an outflow rate of a metabolite excreted out of the cells, wherein said inflow/outflow rates are represented as a growth rate factor; solving the set of differential equations; and generating data representative of the substance-production process.

    摘要翻译： 一种基于代表细胞内代谢物和基因表达的微分方程组，使用细胞模拟物质生产过程的方法，其包括在微分方程组中包含表示为微分方程的细胞的比生长速率; 为所述微分方程组中的参数分配值，其中所述参数中的至少一个被表示为增长率因子; 在微分方程组中并入形成细胞成分的形成速率，其中所述形成速率表示为生长速率因子; 在微分方程组中引入从细胞外部获取的代谢物的流入速率和/或从细胞排出的代谢物的流出速率，其中所述流入/流出速率表示为生长速率因子; 求解微分方程组; 并产生代表物质生产过程的数据。

    Method for production of L-amino acid
    7.
    发明授权
    Method for production of L-amino acid 有权
    L-氨基酸生产方法

    公开(公告)号：US08367371B2

    公开(公告)日：2013-02-05

    申请号：US12420934

    申请日：2009-04-09

    申请人： Yoshinori Tajima ,  Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui

    发明人： Yoshinori Tajima ,  Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui

    IPC分类号： C12P1/00

    CPC分类号： C12N9/88 ,  C12P13/08 ,  C12P13/227

    摘要： A bacterium which belongs to the Enterobacteriaceae family and has an ability to produce an L-amino acid such as L-lysine, L-threonine and L-tryptophan and is modified to enhance glutamic acid decarboxylase activity is cultured in a medium to produce and accumulate the L-amino acid in the medium or cells of the bacterium. Then, the L-amino acid is collected from the medium or the cells.

    摘要翻译： 属于肠杆菌科的具有生产L-赖氨酸，L-苏氨酸和L-色氨酸的L-氨基酸的能力并经过修饰以增强谷氨酸脱羧酶活性的细菌在培养基中培养以产生和积累 细菌的培养基或细胞中的L-氨基酸。 然后，从培养基或细胞收集L-氨基酸。

    Method for determining metabolic flux affecting substance production
    8.
    发明授权
    Method for determining metabolic flux affecting substance production 有权
    测定代谢通量影响物质生产的方法

    公开(公告)号：US07809511B2

    公开(公告)日：2010-10-05

    申请号：US11337580

    申请日：2006-01-24

    申请人： Stephen Van Dien ,  Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui ,  Takuji Ueda ,  Yuichiro Tsuji

    发明人： Stephen Van Dien ,  Shintaro Iwatani ,  Yoshihiro Usuda ,  Kazuhiko Matsui ,  Takuji Ueda ,  Yuichiro Tsuji

    IPC分类号： G06F19/00

    CPC分类号： C12N9/0006 ,  C12P13/08

    摘要： A metabolic flux affecting substance production using cells is determined by 1) creating a stoichiometric matrix based on formulas of biochemical reactions from a substrate through a desired produced substance, 2) selecting the same number of independent metabolic fluxes from all metabolic fluxes as the degree of freedom of the stoichiometric matrix as free fluxes, 3) creating a sufficient number of random combinations of the free fluxes for a statistical analysis and calculating a metabolic flux distribution from each created combination based on the stoichiometric matrix, 4) obtaining a regression equation including a minimum number of free fluxes that shows a correlation with substance production from the calculated metabolic flux distributions by a multivariate statistical analysis, and 5) determining at least one metabolic flux affecting substance production based on a coefficient in the obtained regression equation.

    摘要翻译： 影响使用细胞的物质生产的代谢通量是通过以下方法确定的：1）根据基质通过所需生产物质的生物化学反应的公式产生化学计量矩阵，2）从所有代谢通量中选择相同数量的独立代谢通量， 作为自由通量的化学计量矩阵的自由度，3）产生足够数量的自由通量的随机组合用于统计分析，并且基于化学计量矩阵计算每个创建的组合的代谢通量分布，4）获得包括 通过多变量统计分析从计算的代谢通量分布中显示与物质生产相关的最小数量的自由通量，以及5）基于所获得的回归方程中的系数确定影响物质生产的至少一种代谢通量。