CONTROL ANALYSIS OF METABOLIC SYSTEMS CONSISTING OF UNI- AND/OR MULTIFUNCTIONAL UNITS: APPLICATION TO MODULAR SYSTEMS AND SLIPPING ENZYMES

1995 ◽  
Vol 03 (01) ◽  
pp. 217-230 ◽  
Author(s):  
STEFAN SCHUSTER ◽  
DANIEL KAHN ◽  
HANS V. WESTERHOFF

We present a quantitative method based on Metabolic Control Analysis that makes possible to subdivide large metabolic systems into modules and to integrate the information concerning the flux response of these modules so as to yield understanding of the control structure in terms of the mutual regulation of the modules. This work generalizes previous analyses of overall control properties in that it considers multiple fluxes to connect the modules and reaction networks of any complexity. The approach is applied to slipping enzymes.

Author(s):  
Sophia Tsouka ◽  
Meric Ataman ◽  
Tuure Hameri ◽  
Ljubisa Miskovic ◽  
Vassily Hatzimanikatis

1993 ◽  
Vol 9 (3) ◽  
pp. 221-233 ◽  
Author(s):  
James C. Liao ◽  
Javier Delgado

2014 ◽  
Vol 86 (9) ◽  
pp. 1403-1403
Author(s):  
D. Volke ◽  
B. Engels ◽  
L. Wright ◽  
J. Gershenzon ◽  
S. Jennewein

2020 ◽  
Author(s):  
Sophia Tsouka ◽  
Meric Ataman ◽  
Tuure Hameri ◽  
Ljubisa Miskovic ◽  
Vassily Hatzimanikatis

AbstractThe advancements in genome editing techniques over the past years have rekindled interest in rational metabolic engineering strategies. While Metabolic Control Analysis (MCA) is a well-established method for quantifying the effects of metabolic engineering interventions on flows in metabolic networks and metabolic concentrations, it fails to account for the physiological limitations of the cellular environment and metabolic engineering design constraints. We report here a constraint-based framework based on MCA, Network Response Analysis (NRA), for the rational genetic strain design that incorporates biologically relevant constraints, as well as genome editing restrictions. The NRA core constraints being similar to the ones of Flux Balance Analysis, allow it to be used for a wide range of optimization criteria and with various physiological constraints. We show how the parametrization and introduction of biological constraints enhance the NRA formulation compared to the classical MCA approach, and we demonstrate its features and its ability to generate multiple alternative optimal strategies given several user-defined boundaries and objectives. In summary, NRA is a sophisticated alternative to classical MCA for rational metabolic engineering that accommodates the incorporation of physiological data at metabolic flux, metabolite concentration, and enzyme expression levels.


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