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Despite major environmental and genetic differences, microbial metabolic networks are known to generate consistent physiological outcomes across vastly different organisms. This remarkable robustness suggests that, at least in bacteria,…
The metabolic network plays a crucial role in regulating bacterial metabolism and growth, but it is subject to inherent molecular stochasticity. Previous studies have utilized flux balance analysis and the maximum entropy method to predict…
Understanding the organization of reaction fluxes in cellular metabolism from the stoichiometry and the topology of the underlying biochemical network is a central issue in systems biology. In this task, it is important to devise reasonable…
Which properties of metabolic networks can be derived solely from stoichiometric information about the network's constituent reactions? Predictive results have been obtained by Flux Balance Analysis (FBA), by postulating that cells set…
Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalyzed biochemical reactions, is the most investigated complex intercellular web of molecular interactions. While the topological…
High-throughput experimental techniques and bioinformatics tools make it possible to obtain reconstructions of the metabolism of microbial species. Combined with mathematical frameworks such as flux balance analysis, which assumes that…
The regulation of metabolic activity by tuning enzyme expression levels is crucial to sustain cellular growth in changing environments. Metabolic networks are often studied at steady state using constraint-based models and optimization…
Production of chemicals from engineered organisms in a batch culture involves an inherent trade-off between productivity, yield, and titer. Existing strategies for strain design typically focus on designing mutations that achieve the…
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by…
Genome-scale metabolic models have become a fundamental tool for examining metabolic principles. However, metabolism is not solely characterized by the underlying biochemical reactions and catalyzing enzymes, but also affected by regulatory…
Metagenomics has lowered the barrier to microbial discovery--enabling the identification of novel microbes without isolation--but cultures remain imperative for the deep study of microbes. Cultivation and isolation of non-model microbes…
We review recent work on the statistical mechanics of Von Neumann's growth model and discuss its application to cellular metabolic networks. In this context, we present a detailed analysis of the physiological scenario underlying optimality…
Optimization-based models have been used to predict cellular behavior for over 25 years. The constraints in these models are derived from genome annotations, measured macro-molecular composition of cells, and by measuring the cell's growth…
Flux balance analysis has proven an effective tool for analyzing metabolic networks. In flux balance analysis, reaction rates and optimal pathways are ascertained by solving a linear program, in which the growth rate is maximized subject to…
Biological systems are promising substrates for computation because they naturally process environmental information through complex internal dynamics. In this study, we investigate whether bacterial metabolic models can act as physical…
The solution space of genome-scale models of cellular metabolism provides a map between physically viable flux configurations and cellular metabolic phenotypes described, at the most basic level, by the corresponding growth rates. By…
Understanding the system level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches such as the constraint-based flux balance analyses…
Flux analysis is a class of constraint-based approaches to the study of biochemical reaction networks: they are based on determining the reaction flux configurations compatible with given stoichiometric and thermodynamic constraints. One of…
Deciphering the control principles of metabolism and its interaction with other cellular functions is central to biomedicine and biotechnology. Yet, understanding the efficient control of metabolic fluxes remains elusive for large-scale…
Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell…