A segregated model was proposed to investigate the inherent relationships between growth, substrate consumption, cell differentiation and product formation in a Bacillus subtilis fermentation producing heterologous amylase in a 22-1 bioreactor. The segregated model includes three distinguishable cell states and the transition from vegetative phase to sporangium and finally to mature spore. An age-based population balance model was applied to describe the maturity of sporangium toward the formation of spores. Parameters in the model were determined by fitting the model with experimental data. The model was able to predict the transient behavior of B. subtilis in both batch and fed-batch cultures.