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Identification of metabolic engineering targets through analysis of optimal and...

Identification of optimal genetic manipulation strategies for redirecting substrate uptake towards a desired product is a challenging task owing to the complexity of metabolic networks, esp. in terms of large number of routes leading to the desired product. Algorithms that can exploit the whole range of optimal and suboptimal routes for product formation while respecting the biological objective of the cell are...

Random sampling of elementary flux modes in large-scale metabolic networks

Motivation: The description of a metabolic network in terms of elementary (flux) modes (EMs) provides an important framework for metabolic pathway analysis. However, their application to large networks has been hampered by the combinatorial explosion in the number of modes. In this work, we develop a method for generating random samples of EMs without computing the whole set. Results: Our algorithm is an adapta...

Identification of minimal metabolic pathway models consistent with phenotypic data

The cellular network of metabolic reactions, together with constraints of (ir)reversibility of enzymes, determines the space of all possible steady-state phenotypes. Analysis of large metabolic models, however, is not feasible in real-time and identification of a smaller model without loss of accuracy is desirable for model-based bioprocess optimization and control. To this end, we propose two search algorithms...

Identification of metabolic engineering targets through pathway analysis

Given the complexity of metabolic networks, identification of optimal metabolic intervention strategies for redirecting fluxes towards desired products is a challenging task. Several algorithms based on linear programming and pathway analysis have been proposed. However, there is still a lack of an algorithmic framework that exploits the range of optimal and suboptimal routes and the structural/regulatory prope...

Towards a biologically relevant description of phenotypes based on pathway anal...

In metabolic systems, the cellular network of reactions together with constraints on reversibility of enzymes determine the space of all possible steady-state phenotypes. In actuality, the cell does not invoke the large majority of those in given conditions. We propose a method in two steps to obtain a more precise description of cellular phenotypes through pathway analysis. The first step is based on a modifie...

Selection of thermodynamically feasible and active pathways

Although the network of metabolic reactions, together with constraints of (ir}reversibility of enzymes, determines the space of all potentially possible phenotypes, in actuality the cell does not invoke the large majority of those in given conditions. We propose two methods to restrict the space of potential phenotypes to obtain a more accurate description of cellular phenotypes through pathway analysis. The ca...

Selection of elementary modes for bioprocess control

The lack of model-based information in bioreactor monitoring and control can have a profound impact on biological systems. We therefore aim to develop a model using elementary modes (EMs) that represents the observed phenotype in given environmental conditions suited for bioprocess control. Challenges in the model development were the high number of possible phenotypes of stoichiometric models and the high comp...

Towards bioprocess control based on a reduced metabolic model of Escherichia coli