Title:
METHOD FOR DETERMINING METABOLIC FLUX AFFECTING SUBSTANCE PRODUCTION
Document Type and Number:
WIPO Patent Application WO2005010794
Kind Code:
A3
Abstract:
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.
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Inventors:
VAN DIEN STEPHEN (JP)
IWATANI SHINTARO (JP)
USUDA YOSHIHIRO (JP)
MATSUI KAZUHIKO (JP)
UEDA TAKUJI (JP)
TSUJI YUICHIRO (JP)
IWATANI SHINTARO (JP)
USUDA YOSHIHIRO (JP)
MATSUI KAZUHIKO (JP)
UEDA TAKUJI (JP)
TSUJI YUICHIRO (JP)
Application Number:
PCT/JP2004/011212
Publication Date:
December 01, 2005
Filing Date:
July 29, 2004
Export Citation:
Assignee:
AJINOMOTO KK (JP)
VAN DIEN STEPHEN (JP)
IWATANI SHINTARO (JP)
USUDA YOSHIHIRO (JP)
MATSUI KAZUHIKO (JP)
UEDA TAKUJI (JP)
TSUJI YUICHIRO (JP)
VAN DIEN STEPHEN (JP)
IWATANI SHINTARO (JP)
USUDA YOSHIHIRO (JP)
MATSUI KAZUHIKO (JP)
UEDA TAKUJI (JP)
TSUJI YUICHIRO (JP)
International Classes:
C12N1/00; C12N1/21; C12N15/09; C12N9/04; C12P1/00; C12P13/08; C12Q1/00; (IPC1-7): G06F19/00; C12P13/08
Domestic Patent References:
| WO2002070730A2 | 2002-09-12 | |||
| WO2003029425A2 | 2003-04-10 |
Foreign References:
| US20020142321A1 | 2002-10-03 |
Other References:
CALIK PINAR ET AL: "Serine alkaline protease overproduction capacity of Bacillus licheniformis", ENZYME MICROB TECHNOL; ENZYME AND MICROBIAL TECHNOLOGY 2000 ELSEVIER SCIENCE INC, NEW YORK, NY, USA, vol. 26, no. 1, 2000, pages 45 - 60, XP002345894
VARMA A ET AL: "Metabolic flux balancing: Basic concepts, scientific and practical use", BIO/TECHNOLOGY 1994 UNITED STATES, vol. 12, no. 10, 1994, pages 994 - 998, XP008052270, ISSN: 0733-222X
KLAMT S ET AL: "FluxAnalyzer: Exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps", BIOINFORMATICS, OXFORD UNIVERSITY PRESS, OXFORD,, GB, vol. 19, no. 2, 22 January 2003 (2003-01-22), pages 261 - 269, XP002332882, ISSN: 1367-4803
CHAN CHRISTINA ET AL: "Application of multivariate analysis to optimize function of cultured hepatocytes.", BIOTECHNOLOGY PROGRESS, vol. 19, no. 2, July 2003 (2003-07-01), pages 580 - 598, XP002345895, ISSN: 8756-7938
LEE J-H ET AL: "GLOBAL ANALYSES OF TRANSCRIPTOMES AND PROTEOMES OF A PARENT STRAIN AND AN L-THREONINE-OVERPRODUCING MUTANT STRAIN", JOURNAL OF BACTERIOLOGY, WASHINGTON, DC, US, vol. 185, no. 18, September 2003 (2003-09-01), pages 5442 - 5451, XP009022136, ISSN: 0021-9193
VARMA A ET AL: "Metabolic flux balancing: Basic concepts, scientific and practical use", BIO/TECHNOLOGY 1994 UNITED STATES, vol. 12, no. 10, 1994, pages 994 - 998, XP008052270, ISSN: 0733-222X
KLAMT S ET AL: "FluxAnalyzer: Exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps", BIOINFORMATICS, OXFORD UNIVERSITY PRESS, OXFORD,, GB, vol. 19, no. 2, 22 January 2003 (2003-01-22), pages 261 - 269, XP002332882, ISSN: 1367-4803
CHAN CHRISTINA ET AL: "Application of multivariate analysis to optimize function of cultured hepatocytes.", BIOTECHNOLOGY PROGRESS, vol. 19, no. 2, July 2003 (2003-07-01), pages 580 - 598, XP002345895, ISSN: 8756-7938
LEE J-H ET AL: "GLOBAL ANALYSES OF TRANSCRIPTOMES AND PROTEOMES OF A PARENT STRAIN AND AN L-THREONINE-OVERPRODUCING MUTANT STRAIN", JOURNAL OF BACTERIOLOGY, WASHINGTON, DC, US, vol. 185, no. 18, September 2003 (2003-09-01), pages 5442 - 5451, XP009022136, ISSN: 0021-9193
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