<P><B>Abstract</B></P> <P>In this work, a mechanistic model is developed to simulate the effect of temperature on <I>Saccharomyces cerevisiae</I> growth and ethanol production of batch fermentations. A wide temperature range is used to estimate the temperature-dependent kinetic parameters of the reaction kinetics. Because multi-parameter estimation problems are complex, an optimization-based procedure is used to determine the optimum parameter values. The calculated reaction rates are used to construct a mechanistic fed-batch model. Experimental data from several cycles of very-high-gravity (VHG) ethanol fermentation from sugarcane are used to validate the model. Acceptable predictions are achieved in terms of the residual standard deviation (RSD). In addition, a suitable fermentation temperature profile, nutrient supplementation and micro-aeration during cell treatment are essential factors to obtain a yield of up to 90%, with a productivity of 10.2g/Lh and an ethanol concentration of 120g/L.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Ethanol fermentation by <I>S. cerevisiae</I> is conducted over a wide temperature range. </LI> <LI> A mechanistic kinetic model is developed to predict reaction rates. </LI> <LI> A methodology was proposed to estimate temperature-dependent kinetic parameters. </LI> <LI> The applicability of the kinetic model is validated for VHG ethanol fermentation. </LI> <LI> Conditions to produce ethanol with a higher yield and productivity are studied. </LI> </UL> </P>