@article{BaslerGrimbsEbenhoehetal.2012, author = {Basler, Georg and Grimbs, Sergio and Ebenh{\"o}h, Oliver and Selbig, Joachim and Nikoloski, Zoran}, title = {Evolutionary significance of metabolic network properties}, series = {Interface : journal of the Royal Society}, volume = {9}, journal = {Interface : journal of the Royal Society}, number = {71}, publisher = {Royal Society}, address = {London}, issn = {1742-5689}, doi = {10.1098/rsif.2011.0652}, pages = {1168 -- 1176}, year = {2012}, abstract = {Complex networks have been successfully employed to represent different levels of biological systems, ranging from gene regulation to protein-protein interactions and metabolism. Network-based research has mainly focused on identifying unifying structural properties, such as small average path length, large clustering coefficient, heavy-tail degree distribution and hierarchical organization, viewed as requirements for efficient and robust system architectures. However, for biological networks, it is unclear to what extent these properties reflect the evolutionary history of the represented systems. Here, we show that the salient structural properties of six metabolic networks from all kingdoms of life may be inherently related to the evolution and functional organization of metabolism by employing network randomization under mass balance constraints. Contrary to the results from the common Markov-chain switching algorithm, our findings suggest the evolutionary importance of the small-world hypothesis as a fundamental design principle of complex networks. The approach may help us to determine the biologically meaningful properties that result from evolutionary pressure imposed on metabolism, such as the global impact of local reaction knockouts. Moreover, the approach can be applied to test to what extent novel structural properties can be used to draw biologically meaningful hypothesis or predictions from structure alone.}, language = {en} } @misc{EbenhoehHandorf2009, author = {Ebenh{\"o}h, Oliver and Handorf, Thomas}, title = {Functional classification of genome-scale metabolic networks}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-44975}, year = {2009}, abstract = {We propose two strategies to characterize organisms with respect to their metabolic capabilities. The first, investigative, strategy describes metabolic networks in terms of their capability to utilize different carbon sources, resulting in the concept of carbon utilization spectra. In the second, predictive, approach minimal nutrient combinations are predicted from the structure of the metabolic networks, resulting in a characteristic nutrient profile. Both strategies allow for a quantification of functional properties of metabolic networks, allowing to identify groups of organisms with similar functions. We investigate whether the functional description reflects the typical environments of the corresponding organisms by dividing all species into disjoint groups based on whether they are aerotolerant and/or photosynthetic. Despite differences in the underlying concepts, both measures display some common features. Closely related organisms often display a similar functional behavior and in both cases the functional measures appear to correlate with the considered classes of environments. Carbon utilization spectra and nutrient profiles are complementary approaches toward a functional classification of organism-wide metabolic networks. Both approaches contain different information and thus yield different clusterings, which are both different from the classical taxonomy of organisms. Our results indicate that a sophisticated combination of our approaches will allow for a quantitative description reflecting the lifestyles of organisms.}, language = {en} } @misc{KartalEbenhoeh2009, author = {Kartal, {\"O}nder and Ebenh{\"o}h, Oliver}, title = {Ground state robustness as an evolutionary design principle in signaling networks}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-44982}, year = {2009}, abstract = {The ability of an organism to survive depends on its capability to adapt to external conditions. In addition to metabolic versatility and efficient replication, reliable signal transduction is essential. As signaling systems are under permanent evolutionary pressure one may assume that their structure reflects certain functional properties. However, despite promising theoretical studies in recent years, the selective forces which shape signaling network topologies in general remain unclear. Here, we propose prevention of autoactivation as one possible evolutionary design principle. A generic framework for continuous kinetic models is used to derive topological implications of demanding a dynamically stable ground state in signaling systems. To this end graph theoretical methods are applied. The index of the underlying digraph is shown to be a key topological property which determines the so-called kinetic ground state (or off-state) robustness. The kinetic robustness depends solely on the composition of the subdigraph with the strongly connected components, which comprise all positive feedbacks in the network. The component with the highest index in the feedback family is shown to dominate the kinetic robustness of the whole network, whereas relative size and girth of these motifs are emphasized as important determinants of the component index. Moreover, depending on topological features, the maintenance of robustness differs when networks are faced with structural perturbations. This structural off-state robustness, defined as the average kinetic robustness of a network's neighborhood, turns out to be useful since some structural features are neutral towards kinetic robustness, but show up to be supporting against structural perturbations. Among these are a low connectivity, a high divergence and a low path sum. All results are tested against real signaling networks obtained from databases. The analysis suggests that ground state robustness may serve as a rationale for some structural peculiarities found in intracellular signaling networks.}, language = {en} } @article{RuzanskiSmirnovaRejzeketal.2013, author = {Ruzanski, Christian and Smirnova, Julia and Rejzek, Martin and Cockburn, Darrell and Pedersen, Henriette L. and Pike, Marilyn and Willats, William G. T. and Svensson, Birte and Steup, Martin and Ebenh{\"o}h, Oliver and Smith, Alison M. and Field, Robert A.}, title = {A bacterial glucanotransferase can replace the complex maltose metabolism required for starch to sucrose conversion in leaves at night}, series = {The journal of biological chemistry}, volume = {288}, journal = {The journal of biological chemistry}, number = {40}, publisher = {American Society for Biochemistry and Molecular Biology}, address = {Bethesda}, issn = {0021-9258}, doi = {10.1074/jbc.M113.497867}, pages = {28581 -- 28598}, year = {2013}, abstract = {Controlled conversion of leaf starch to sucrose at night is essential for the normal growth of Arabidopsis. The conversion involves the cytosolic metabolism of maltose to hexose phosphates via an unusual, multidomain protein with 4-glucanotransferase activity, DPE2, believed to transfer glucosyl moieties to a complex heteroglycan prior to their conversion to hexose phosphate via a cytosolic phosphorylase. The significance of this complex pathway is unclear; conversion of maltose to hexose phosphate in bacteria proceeds via a more typical 4-glucanotransferase that does not require a heteroglycan acceptor. It has recently been suggested that DPE2 generates a heterogeneous series of terminal glucan chains on the heteroglycan that acts as a glucosyl buffer to ensure a constant rate of sucrose synthesis in the leaf at night. Alternatively, DPE2 and/or the heteroglycan may have specific properties important for their function in the plant. To distinguish between these ideas, we compared the properties of DPE2 with those of the Escherichia coli glucanotransferase MalQ. We found that MalQ cannot use the plant heteroglycan as an acceptor for glucosyl transfer. However, experimental and modeling approaches suggested that it can potentially generate a glucosyl buffer between maltose and hexose phosphate because, unlike DPE2, it can generate polydisperse malto-oligosaccharides from maltose. Consistent with this suggestion, MalQ is capable of restoring an essentially wild-type phenotype when expressed in mutant Arabidopsis plants lacking DPE2. In light of these findings, we discuss the possible evolutionary origins of the complex DPE2-heteroglycan pathway.}, language = {en} }