Abstract: Metabolic Control Analysis (MCA) is a mathematical theory stemming from elec-trical engineering network analysis applied to biological systems. Availability of annotated genome, metabolomics and proteomics of numerous industrial important microorganism leads fundamental research of industrial microbiology “in silico“. From engineering point of view, open are possibilities for computer design of synthetic genome for development of new tech-nologies, most importantly for bioenergetics based on synthetic microorganism with inte-grated photosynthesis and fermentation metabolisms. The main obstacles toward this far reaching goal are not in chemical synthesis of genome, but rather in biological and computer analysis of intricate metabolism control on a molecular level. At present, most of MCA analy-sis is based on steady state (homeostatic constraint) analysis and study of “one factor at a time” infinitesimal effects of perturbations of each individual enzyme and metabolite concen-tration on metabolic fluxes and individual reaction rates. This work introduces the concept of global sensitivity based on simultaneous variation of a complete set of enzymes and metabo-lite concentrations (elasticities) in finite ranges of activities (concentrations). Perturbations are defined by corresponding finite ranges of concentrations and corresponding general probabil-ity density distributions. The flux sensitivities are determined as first and second order rela-tive multidimensional variances. The first order effects are reflection of variation of each in-dividual enzyme. Importantly, the second order effects imply synergic effects of the whole ensemble of enzymes which completely escapes in the traditional MCA analysis. The disper-sions of fluxes due to each enzyme are evaluated through computer simulation and Fourier Amplitude Sensitivity Test algorithm. The implications of the proposed theory are demon-strated by computer simulation of theoretical metabolism pathways and experimental analysis of E. coli central metabolism unsteady perturbation by glucose impulse.

Brief Biography of the Speaker:
Zelimir Kurtanjek was born in 1946 in Zagreb, Croa-tia. He graduated in 1971 with engineering degree in physics from the Department of Sci-ences, University of Zagreb. He completed postgraduate studies in Technical Cybernetics at Faculty of Technology, University of Zagreb. In 1975 he enrolled at the postgraduate study in chemical engineering at the Department of Chemical Engineering, The University of Houston, TX, USA. In 1979 he received doctoral degree under mentorship of Prof. Dan Luss in the Laboratory for Reaction Engineering. He completed his postdoctoral studies with Prof. G. Froment at the Department of Chemical Engineering, University of Gent, Belgium. During 1991. he was a visiting professor through EU project TEMPUS at the Department of Biologi-cal Sciences, University of Ulster, Coleraine, Northern Ireland. Since 1980 he is employed at the University of Zagreb, Faculty of Food Technology and Biotechnology, University of Za-greb as a professor of chemical engineering. He is teaching reactor engineering, mathematical modeling and process control to students of biochemical, chemical and food engineering.
In his scientific work he is interested in modeling and control of reactors, modeling of bioprocesses and food processes, and application of AI methods in modeling and process con-trol. He has published over 50 papers in international and national journals. Since 1976 he is a member of American Institute of Chemical Engineers, a delegate of Croatia in European Fed-eration of Biotechnology, and also is a member of Croatian Society of Chemical Engineers, Croatian Society of Biotechnology, and Croatian Technical Academy. He is editor in chief of Chemical and Biochemical Engineering Quarterly and a member of the editorial board of Food Technology and Biotechnology journals.

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