@article{SteuerGrossSelbigetal.2006,
  author    = {Steuer, Ralf and Gross, Thilo and Selbig, Joachim and Blasius, Bernd},
  title     = {Structural kinetic modeling of metabolic networks},
  series = {Proceedings of the National Academy of Sciences of the United States of America},
  volume    = {103},
  journal   = {Proceedings of the National Academy of Sciences of the United States of America},
  number    = {32},
  publisher = {National Academy of Sciences},
  address   = {Washington},
  issn      = {0027-8424},
  doi       = {10.1073/pnas.0600013103},
  pages     = {11868 -- 11873},
  year      = {2006},
  abstract  = {To develop and investigate detailed mathematical models of metabolic processes is one of the primary challenges in systems biology. However, despite considerable advance in the topological analysis of metabolic networks, kinetic modeling 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 quantitative account of the dynamical capabilities of a metabolic system, without requiring any explicit information about the 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 statistical exploration of the comprehensive parameter space. The method is exemplified on two paradigmatic metabolic systems: the glycolytic pathway of yeast and a realistic-scale representation of the photosynthetic Calvin cycle.},
  language  = {en}
}
@phdthesis{JadhavSudam2019,
  author    = {Jadhav Sudam, Sagar},
  title     = {Metabolic regulation and key genes of tomato secondary metabolism},
  doi       = {10.25932/publishup-42447},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-424478},
  school      = {Universit{\"a}t Potsdam},
  pages     = {x, 149},
  year      = {2019},
  abstract  = {Domestication syndrome has resulted in the large loss of genetic variation of crop plants. Because of such genetic loss, productivity of various beneficial secondary (specialized) metabolites that protect against abiotic/biotic stresses, has been narrowed in many domesticated crops. Many key regulators or structural genes of secondary metabolic pathways in the domesticated as well as wild tomatoes are still largely unknown. In recent studies, metabolic quantitative trait loci (mQTL) analysis using the population of introgression lines (ILs), each containing a single introgression from Solanum pennellii (wild tomato) in the genetic background of domesticated tomato (M82, Solanum lycopersicum), has been used for investigation of metabolic regulation and key genes involved in both primary and secondary metabolism. In this thesis, three research projects, i) understanding of metabolic linkage between branched chain amino acids (BCAAs) and secondary metabolism using antisense lines of BCAAs metabolic genes, ii) investigation of novel key genes involved in tomato secondary metabolism and fruit ripening, iii) mapping of drought stress responsive mQTLs in tomato, are presented and discussed. In the first part, metabolic linkage between leucine and secondary metabolism is investigated by analyzing antisense lines of four key genes (ketol-acid reductoisomerase, KARI; dihydroxy-acid dehydratase, DHAD; isopropylmalate dehydratase, IPMD and branched chain aminotransferases1, BCAT1) found previously in mQTL of leucine contents. Obtained results indicate that KARI might be a rate limiting enzyme for iC5 acyl-sucrose synthesis in young leaf but not in red ripe fruits. By integrating obtained results with previous reports, inductive metabolic linkage between BCAAs and other secondary metabolic pathways at DHAD transcriptional levels in fruit is proposed. In the second part, candidate genes that are involved in secondary metabolism and fruit ripening in tomato were found by the approach of expression quantitative trait loci (eQTL) analysis. To predict functions of those candidate genes, functional validation by virus induced gene silencing and transient overexpression were performed. Results obtained by analyzing T0 overexpression and artificial miRNA lines for some of those candidates confirm their predicted functions, for example involved in fruit ripening (WD40, Solyc04g005020) and iC5 acyl-sucrose synthesis (P450, Solyc03g111940). In the third part, mapping of drought stress responsive mQTLs was performed using 57 S. pennellii ILs population. Evaluation of genetic architecture of mQTL analysis resulted in identifying drought responsive ILs (11-2, 8-3-1, 10-1-1 and 3-1). Location of well characterized regulators in these ILs helped to filter potential new key genes involved in drought stress tolerance. Obtained results suggests us our approaches could be viable for narrowing down potential candidates involved in creating interspecific variation in secondary metabolite content and at the level of fruit ripening.},
  language  = {en}
}
@article{KartalMahlowSkupinetal.2011,
  author    = {Kartal, Oender and Mahlow, Sebastian and Skupin, Alexander and Ebenhoeh, Oliver},
  title     = {Carbohydrate-active enzymes exemplify entropic principles in metabolism},
  series = {Molecular systems biology},
  volume    = {7},
  journal   = {Molecular systems biology},
  number    = {10},
  publisher = {Nature Publ. Group},
  address   = {New York},
  issn      = {1744-4292},
  doi       = {10.1038/msb.2011.76},
  pages     = {11},
  year      = {2011},
  abstract  = {Glycans comprise ubiquitous and essential biopolymers, which usually occur as highly diverse mixtures. The myriad different structures are generated by a limited number of carbohydrate-active enzymes (CAZymes), which are unusual in that they catalyze multiple reactions by being relatively unspecific with respect to substrate size. Existing experimental and theoretical descriptions of CAZyme-mediated reaction systems neither comprehensively explain observed action patterns nor suggest biological functions of polydisperse pools in metabolism. Here, we overcome these limitations with a novel theoretical description of this important class of biological systems in which the mixing entropy of polydisperse pools emerges as an important system variable. In vitro assays of three CAZymes essential for central carbon metabolism confirm the power of our approach to predict equilibrium distributions and non-equilibrium dynamics. A computational study of the turnover of the soluble heteroglycan pool exemplifies how entropy-driven reactions establish a metabolic buffer in vivo that attenuates fluctuations in carbohydrate availability. We argue that this interplay between energy- and entropy-driven processes represents an important regulatory design principle of metabolic systems.},
  language  = {en}
}
@article{AraujoNunesNesiNikoloskietal.2012,
  author    = {Araujo, Wagner L. and Nunes-Nesi, Adriano and Nikoloski, Zoran and Sweetlove, Lee J. and Fernie, Alisdair R.},
  title     = {Metabolic control and regulation of the tricarboxylic acid cycle in photosynthetic and heterotrophic plant tissues},
  series = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology},
  volume    = {35},
  journal   = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology},
  number    = {1},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0140-7791},
  doi       = {10.1111/j.1365-3040.2011.02332.x},
  pages     = {1 -- 21},
  year      = {2012},
  abstract  = {The tricarboxylic acid (TCA) cycle is a crucial component of respiratory metabolism in both photosynthetic and heterotrophic plant organs. All of the major genes of the tomato TCA cycle have been cloned recently, allowing the generation of a suite of transgenic plants in which the majority of the enzymes in the pathway are progressively decreased. Investigations of these plants have provided an almost complete view of the distribution of control in this important pathway. Our studies suggest that citrate synthase, aconitase, isocitrate dehydrogenase, succinyl CoA ligase, succinate dehydrogenase, fumarase and malate dehydrogenase have control coefficients flux for respiration of -0.4, 0.964, -0.123, 0.0008, 0.289, 0.601 and 1.76, respectively; while 2-oxoglutarate dehydrogenase is estimated to have a control coefficient of 0.786 in potato tubers. These results thus indicate that the control of this pathway is distributed among malate dehydrogenase, aconitase, fumarase, succinate dehydrogenase and 2-oxoglutarate dehydrogenase. The unusual distribution of control estimated here is consistent with specific non-cyclic flux mode and cytosolic bypasses that operate in illuminated leaves. These observations are discussed in the context of known regulatory properties of the enzymes and some illustrative examples of how the pathway responds to environmental change are given.},
  language  = {en}
}