Many kinetic models of Escherichia coli central metabolism have been built, but few models accurately reproduced the dynamic behaviors of wild type and multiple genetic mutants. In 2016, our latest kinetic model improved problems of existing models to reproduce the cell growth and glucose uptake of wild type, Delta pykA:pyliF and Delta pgi in a batch culture, while it overestimated the glucose uptake and cell growth rates of Delta ppc and hardly captured the typical characteristics of the glyoxylate and TCA cycle fluxes for Delta pgi and Delta ppc. Such discrepancies between the simulated and experimental data suggested biological complexity. In this study, we overcame these problems by assuming critical mechanisms regarding the OAA-regulated isocitrate dehydrogenase activity, aceBAK gene regulation and growth suppression. The present model accurately predicts the extracellular and intracellular dynamics of wild type and many gene knockout mutants in batch and continuous cultures. It is now the most accurate, detailed kinetic model of E. coli central carbon metabolism and will contribute to advances in mathematical modeling of cell factories. (C) 2017, The Society for Biotechnology, Japan. All rights reserved.