ensemble kinetic modeling of metabolic networks from dynamic metabolic profiles整体动力学建模动态代谢的代谢网络.pdfVIP

Metabolites 2012, 2, 891-912; doi:10.3390/metabo2040891 OPEN ACCESS metabolites ISSN 2218-1989 /journal/metabolites/ Article Ensemble Kinetic Modeling of Metabolic Networks from Dynamic Metabolic Profiles Gengjie Jia 1, Gregory Stephanopoulos 2 and Rudiyanto Gunawan 3,* 1 Chemical and Pharmaceutical Engineering, Singapore-MIT Alliance, Singapore 117576;Singapore-MIT Alliance, Singapore 117576, Singapore; E-Mail: jiagengjie@.sg (G.J.) 2 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; E-Mail: gregstep@ (G.S.) 3 Institute for Chemical and Bioengineering, ETH Zurich, 8093 Zurich, Switzerland * Author to whom correspondence should be addressed; E-Mail: rudi.gunawan@chem.ethz.ch; Tel.: +41 44 633 21 34; Fax: +41 44 633 12 52. Received: 14 September 2012; in revised form: 2 November 2012 / Accepted: 5 November 2012 / Published: 12 November 2012 Abstract: Kinetic modeling of metabolic pathways has important applications in metabolic engineering, but significant challenges still remain. The difficulties faced vary from finding best-fit parameters in a highly multidimensional search space to incomplete parameter identifiability. To meet some of these challenges, an ensemble modeling method is developed for characterizing a subset of kinetic parameters that give statistically equivalent goodness-of-fit to time series concentration data. The method is based on the incremental identification approach, where the parameter estimation is