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Flux Balance Analysis with Molecular Crowding

详细技术说明

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*Abstract

An important aim of systems biology is the identification of the organizing principles and fundamental constraints that characterize the function of molecular interaction networks and the limits of an organism's phenotypic diversity, with the long-term practical goal of being able to predict a cell's or organism's phenotypic response on a given environmental or genetic/ epigenetic change. Flux balance-based modeling approaches, combining the constraints imposed by the metabolic network's structure with e.g., mass- or energy conservation principles, are especially successful in providing experimentally testable predictions on an organism's metabolic flux state and growth rate. A relative shortcoming of these approaches, however, is that they do not take into account the physical and spatial constraints resulting from the cell's unique intracellular milieu.In this invention, the inventors have developed a modified form of flux balance analysis that incorporates a solvent capacity constraint for the attainable enzyme concentrations within the crowded cytoplasm. Using this model they are able to successfully predict the maximum growth rate of wild type and mutant bacterial cells on single carbon sources, the dynamic patterns of substrate utilization from a mixed-substrate growth medium, and the global reorganization of metabolic activity in cells when they are shifted from low to high growth rates.This Invention is believed to represent a substantial extension of flux balance-based modeling capabilities, and as such will be of interest to the biotechnology and biomodeling industry.Applications:1. Calculating cell growth in various environments and genetic backgrounds2. Calculating the mode and order of substrate utilization from a growth medium3. Calculating metabolic flux reorganization in various environments and at various growth rates.Non Provisional Patent Application Filed

*Principal Investigation

Name: Zoltan Oltvai

Department: Med-Pathology

Name: Alexei Vazquez, Member

Department:

国家/地区

美国