A generalized reference state extends the applicability of approximative kinetics in metabolic engineering

作者：Nikerel Emrah^*; Verheijen Peter J T; Heijnen Joseph J

来源：Journal of Chemical Technology and Biotechnology, 2012, 87(12): 1694-1701.

DOI：10.1002/jctb.3819

BACKGROUND: The use of approximative kinetics for modeling enzyme kinetics and for metabolic engineering purposes has become increasingly attractive. Despite a list of advantages, the proposed use of a steady state for reference limits the use of such kinetic formats. %26lt;br%26gt;RESULTS: Here, to avoid these limitations, an alternative formulation is proposed for the linlog approximative kinetics introducing a characteristic set for normalization. The necessary equations for the parameter (elasticities and the reaction rate of the characteristic set) estimation framework using data obtained from various types of perturbation experiments are given. The use of the new formulation is exemplified with three illustrative examples: parameter estimation in steady state and in dynamic experiments; and prediction of the effect of a mutation in enzyme kinetics properties. The implications of the new formulation are discussed. %26lt;br%26gt;CONCLUSIONS: By introducing a so-called characteristic set, we show that the approximative quality of this kinetics is improved and this formulation can be used to analyze and model data from a broader set of experimental scenarios.