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Ralf Steuer

Publications and source records attributed to Ralf Steuer.

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Evaluating the stoichiometric and energetic constraints of cyanobacterial diurnal growth

Cyanobacteria are an integral part of the Earth's biogeochemical cycles and a promising resource for the synthesis of renewable bioproducts from atmospheric CO2 . Growth and metabolism of cyanobacteria are inherently tied to the diurnal rhythm of light availability. As yet, however, insight into the stoichiometric and energetic constraints of cyanobacterial diurnal growth is limited. Here, we develop a computational platform to evaluate the optimality of diurnal phototrophic growth using a high-quality genome-scale metabolic reconstruction of the cyanobacterium Synechococcus elongatus PCC 7942. We formulate phototrophic growth as a self-consistent autocatalytic process and evaluate the resulting time-dependent resource allocation problem using constraint-based analysis. Based on a narrow and well defined set of parameters, our approach results in an ab initio prediction of growth properties over a full diurnal cycle. In particular, our approach allows us to study the optimality of metabolite partitioning during diurnal growth. The cyclic pattern of glycogen accumulation, an emergent property of the model, has timing characteristics that are shown to be a trade-off between conflicting cellular objectives. The approach presented here provides insight into the time-dependent resource allocation problem of phototrophic diurnal growth and may serve as a general framework to evaluate the optimality of metabolic strategies that evolved in photosynthetic organisms under diurnal conditions.

q-bio.MN

Enzyme allocation problems in kinetic metabolic networks: Optimal solutions are elementary flux modes

The survival and proliferation of cells and organisms require a highly coordinated allocation of cellular resources to ensure the efficient synthesis of cellular components. In particular, the total enzymatic capacity for cellular metabolism is limited by finite resources that are shared between all enzymes, such as cytosolic space, energy expenditure for amino-acid synthesis, or micro-nutrients. While extensive work has been done to study constrained optimization problems based only on stoichiometric information, mathematical results that characterize the optimal flux in kinetic metabolic networks are still scarce. Here, we study constrained enzyme allocation problems with general kinetics, using the theory of oriented matroids. We give a rigorous proof for the fact that optimal solutions of the non-linear optimization problem are elementary flux modes. This finding has significant consequences for our understanding of optimality in metabolic networks as well as for the identification of metabolic switches and the computation of optimal flux distributions in kinetic metabolic networks.

q-bio.MN

Structural Kinetic Modeling of Metabolic Networks

To develop and investigate detailed mathematical models of cellular metabolic processes is one of the primary challenges in systems biology. However, despite considerable advance in the topological analysis of metabolic networks, explicit kinetic modeling based on differential equations is still often severely hampered by inadequate knowledge of the enzyme-kinetic rate laws and their associated parameter values. Here we propose a method that aims to give a detailed and quantitative account of the dynamical capabilities of metabolic systems, without requiring any explicit information about the particular functional form of the rate equations. Our approach is based on constructing a local linear model at each point in parameter space, such that each element of the model is either directly experimentally accessible, or amenable to a straightforward biochemical interpretation. This ensemble of local linear models, encompassing all possible explicit kinetic models, then allows for a systematic statistical exploration of the comprehensive parameter space. The method is applied to two paradigmatic examples: The glycolytic pathway of yeast and a realistic-scale representation of the photosynthetic Calvin cycle.

q-bio.MN