%0 Journal Article %1 ISI:000237445000006 %A Wahl, SA %A Takors, R %A Wiechert, W %C 111 RIVER ST, HOBOKEN, NJ 07030 USA %D 2006 %I JOHN WILEY & SONS INC %J BIOTECHNOLOGY AND BIOENGINEERING %K myown %N 2 %P 263-272 %R 10.1002/bit.20837 %T Interpretation of metabolic flux maps by limitation potentials and constrained limitation sensitivities %U https://doi.org/10.1002/bit.20837 %V 94 %X Two new concepts, ``Limitation Potential'' and ``Constraint Limitation Sensitivity'' are introduced that use definitions derived from metabolic flux analysis (MFA) and metabolic network analysis (MNA). They are applied to interpret a measured flux distribution in the context of all possible flux distributions and thus combine MFA with MNA. The proposed measures are used to quantify and compare the influence of intracellular fluxes on the production yield. The methods are purely based on the stoichiometry of the network and constraints that are given from irreversible fluxes. In contrast to metabolic control analysis (MCA), within this approach no information about the kinetic mechanisms are needed. A limitation potential (LP) is defined as the reduction, of the reachable (theoretical) maximum by a measured flux. Measured fluxes that strongly narrow the reachable maximum are assumed to be limiting as the network has no ability to counterbalance the restriction due to the observed flux. In a second step, the sensitivity of the reduced maximum is regarded. This measure provides information about the necessitated changes to reach higher yields. The methods are applied to interpret the capabilities of a network based on measured fluxes for a L-phenylalanine producer. The strain was examined by a series of experiments and three flux maps of the production phase are analyzed. It can be shown that the reachable, yield is drastically reduced by the measured efflux into the TCA cycle, while the oxidative pentose-phosphate pathway only plays a secondary role on the reachable maximum. (c) 2006 Wiley Periodicals, Inc.

@article{ISI:000237445000006, abstract = {{Two new concepts, ``Limitation Potential{''} and ``Constraint Limitation Sensitivity{''} are introduced that use definitions derived from metabolic flux analysis (MFA) and metabolic network analysis (MNA). They are applied to interpret a measured flux distribution in the context of all possible flux distributions and thus combine MFA with MNA. The proposed measures are used to quantify and compare the influence of intracellular fluxes on the production yield. The methods are purely based on the stoichiometry of the network and constraints that are given from irreversible fluxes. In contrast to metabolic control analysis (MCA), within this approach no information about the kinetic mechanisms are needed. A limitation potential (LP) is defined as the reduction, of the reachable (theoretical) maximum by a measured flux. Measured fluxes that strongly narrow the reachable maximum are assumed to be limiting as the network has no ability to counterbalance the restriction due to the observed flux. In a second step, the sensitivity of the reduced maximum is regarded. This measure provides information about the necessitated changes to reach higher yields. The methods are applied to interpret the capabilities of a network based on measured fluxes for a L-phenylalanine producer. The strain was examined by a series of experiments and three flux maps of the production phase are analyzed. It can be shown that the reachable, yield is drastically reduced by the measured efflux into the TCA cycle, while the oxidative pentose-phosphate pathway only plays a secondary role on the reachable maximum. (c) 2006 Wiley Periodicals, Inc.}}, added-at = {2018-06-08T11:26:35.000+0200}, address = {{111 RIVER ST, HOBOKEN, NJ 07030 USA}}, affiliation = {{Wiechert, W (Reprint Author), Forschungszentrum Julich GmbH, Inst Biotechnol 2, Julich, Germany. Forschungszentrum Julich GmbH, Inst Biotechnol 2, Julich, Germany. Univ Siegen, Inst Syst Engn, Dept Simulat, D-57068 Siegen, Germany.}}, author = {Wahl, SA and Takors, R and Wiechert, W}, author-email = {{wiechert@simtec.mb.uni-siegen.de}}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2afb0d6390fe1432dcb7569a60a798811/ralftakors}, da = {{2018-01-26}}, doc-delivery-number = {{041HJ}}, doi = {{10.1002/bit.20837}}, interhash = {af3332f0a9ea5cf4946e4a0525b9e980}, intrahash = {afb0d6390fe1432dcb7569a60a798811}, issn = {{0006-3592}}, journal = {{BIOTECHNOLOGY AND BIOENGINEERING}}, journal-iso = {{Biotechnol. Bioeng.}}, keywords = {myown}, keywords-plus = {{ESCHERICHIA-COLI; PATHWAY ANALYSIS; SENSOR REACTOR; SYSTEMS; DISTRIBUTIONS; RATES}}, language = {{English}}, month = {{JUN 5}}, number = {{2}}, number-of-cited-references = {{21}}, orcid-numbers = {{Wahl, Aljoscha/0000-0003-2120-1859}}, pages = {{263-272}}, publisher = {{JOHN WILEY \& SONS INC}}, research-areas = {{Biotechnology \& Applied Microbiology}}, researcherid-numbers = {{Wahl, Aljoscha/B-1839-2013}}, times-cited = {{2}}, timestamp = {2018-06-08T09:26:35.000+0200}, title = {{Interpretation of metabolic flux maps by limitation potentials and constrained limitation sensitivities}}, type = {{Article}}, unique-id = {{ISI:000237445000006}}, url = {https://doi.org/10.1002/bit.20837}, usage-count-last-180-days = {{0}}, usage-count-since-2013 = {{4}}, volume = {{94}}, web-of-science-categories = {{Biotechnology \& Applied Microbiology}}, year = {{2006}} }