A method for analysis and design of metabolism using metabolomics data and kinetic models: Application on lipidomics using a novel kinetic model of sphingolipid metabolism

Article Article scientifique Article A method for analysis and design of metabolism using metabolomics data and kinetic models: Application on lipidomics using a novel kinetic model of sphingolipid metabolism eng 2016 author Savoglidis Georgios author Xavier da Silva dos Santos Aline author Riezman Isabelle 23201 author Angelino Paolo author Riezman Howard 134430 author Hatzimanikatis Vassily 688418 46-62 10.1016/j.ymben.2016.04.002 1096-7176 https://linkinghub.elsevier.com/retrieve/pii/S1096717616300106 We present a model-based method, designated Inverse Metabolic Control Analysis (IMCA), which can be used in conjunction with classical Metabolic Control Analysis for the analysis and design of cellular metabolism. We demonstrate the capabilities of the method by first developing a comprehensively curated kinetic model of sphingolipid biosynthesis in the yeast Saccharomyces cerevisiae. Next we apply IMCA using the model and integrating lipidomics data. The combinatorial complexity of the synthesis of sphingolipid molecules, along with the operational complexity of the participating enzymes of the pathway, presents an excellent case study for testing the capabilities of the IMCA. The exceptional agreement of the predictions of the method with genome-wide data highlights the importance and value of a comprehensive and consistent engineering approach for the development of such methods and models. Based on the analysis, we identified the class of enzymes regulating the distribution of sphingolipids among species and hydroxylation states, with the D-phospholipase SPO14 being one of the most prominent. The method and the applications presented here can be used for a broader, model-based inverse metabolic engineering approach. Inverse metabolic engineering Strain design Nonlinear kinetic models Lipid metabolism Sphingolipid regulation Lipidomics Dewey 540 39 Département de biochimie 144 false Metabolic Engineering 37 7fb84e56-ec3e-4e99-881e-66a83f3ea1e1 Article (Published version) Public AMethod_HR_16.pdf 2037245 application/pdf openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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A method for analysis and design of metabolism using metabolomics data and kinetic models: Application on lipidomics using a novel kinetic model of sphingolipid metabolism	Metabolic Engineering			2016	213	100

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Hatzimanikatis, Vassily