In this paper, an optimum-seeking controller is proposed to minimize the output substrate concentration of a configuration of two interconnected auto-catalytic systems in the presence of input substrate concentration disturbances and model parameter uncertainty. The proposed multi-configuration bioreactor system improves the optimum performance that could be achieved with a single well-mixed reactor. The optimum-seeking controller provides a real-time optimization tool that allows one to achieve the full capability of the multi-configuration system for a wide range of bioreactor kinetics. Simulation results demonstrates the applicability of the technique for a bioreactor system with slowly time-varying parameters.